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K Imada,
T Dainichi,
A Yokomizo,
T Tsunoda,
Y H Song,
A Nagasaki,
D Sawamura,
W Nishie,
H Shimizu,
S Fukagawa, K Urabe,
M Furue,
T Hashimoto,
S Naito
British Journal of Dermatology 05/2009; 160(6):1350-3. · 3.67 Impact Factor
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ABSTRACT: The proteins p53, p63 and p73 are known to be overexpressed and to play important roles in the pathogenesis of many tumours, but the expression of p63 and p73 has not previously been investigated in extramammary Paget's disease (EMPD).
To investigate the potential contribution of p53, p63 and p73 in the pathogenesis of EMPD.
In total, 35 paraffin wax-embedded tissue samples from patients with EMPD were examined using immunohistochemical staining for p53, p63 and p73.
All of the 35 EMPD specimens, including all 6 invasive EMPD and 2 metastatic lymph-node specimens, showed nuclear overexpression of both p53 and p73. The expression levels (percentage of positive cells) of p53 and p73 (90.66 +/- 12.53% and 80.20 +/- 13.07%) in EMPD were significantly higher than those of normal skin. There was a significant correlation between the expression levels of p53 and p73 in EMPD. In 29 of 35 EMPD specimens, there was no nuclear expression of p63, and weak or moderate staining was found in only 6 specimens. The expression level of p63 in EMPD was significantly less than that in normal skin.
Our study shows that the concordant overexpression of p53 and p73 and the decreased expression of p63 may play a pivotal role in the pathogenesis of EMPD. The decreased expression of p63 may play a more important role in the pathogenesis of EMPD than the overexpression of p53 and p73.
Clinical and Experimental Dermatology 08/2008; 33(5):634-40. · 1.20 Impact Factor
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ABSTRACT: Background Patients with systemic sclerosis (SSc) frequently suffer from recalcitrant digital ulceration because of impaired cutaneous blood flow (CBF). A simple and accurate CBF measurement would be helpful to evaluate the disease status and efficacy of treatment in such patients. Objectives To examine the feasibility of a newly developed, micromachined integrated laser blood flowmeter (MILBF) for evaluation of abnormal CBF responses in patients with SSc. Methods CBF of finger pulp was measured in eight patients with SSc and in six healthy controls using MILBF. CBF in the steady state and the responses to the arm-raising test and cold provocation were assessed. The therapeutic efficacy of a single and an intensive prostaglandin E(1) (PGE(1)) infusion treatment was also evaluated in some of the SSc patients. Results The patients with SSc showed significantly lower steady-state CBF than controls. The rate of blood flow with cold provocation and the velocity of blood flow recovery after cold provocation (VR-CP) tended to be lower in patients with SSc. Augmentation of amplitude of the digital pulse wave by arm raising (AA-AR) was observed in controls, but not in patients with SSc. We also found that VR-CP and AA-AR may be good markers for evaluating the efficacy of vasodilatory treatment. It should be noted that the examined patients did not complain of any pain and/or distress during the arm-raising test, as opposed to during cold provocation. Conclusions CBF assessment using MILBF and an arm-raising test is accurate, noninvasive and well tolerated and thus the combination may be a better alternative method to evaluate abnormal CBF and efficacy of treatment in patients with SSc.
British Journal of Dermatology 11/2007; 157(4):690-7. · 3.67 Impact Factor
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ABSTRACT: The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD).
To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them.
Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2.
Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD.
Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.
British Journal of Dermatology 10/2006; 155(3):586-91. · 3.67 Impact Factor
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H J Liu,
Y Moroi,
T Masuda,
S Yasumoto,
H Kokuba,
S Imafuku,
T Koga,
T Tetsuya,
Y T Tu,
H Aburatani,
M Furue, K Urabe
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ABSTRACT: Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD).
To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them.
Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL.
Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression.
Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.
British Journal of Dermatology 06/2006; 154(5):926-32. · 3.67 Impact Factor
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H.J. Liu,
Y. Moroi,
T. Masuda,
S. Yasumoto,
H. Kokuba,
S. Imafuku,
T. Koga,
T. Tetsuya,
Y.T. Tu,
H. Aburatani,
M. Furue, K. Urabe
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ABSTRACT: Background Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD).Objectives To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them.Methods Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL.Results Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression.Conclusions Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.
British Journal of Dermatology 04/2006; 154(5):926 - 932. · 3.67 Impact Factor
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British Journal of Dermatology 04/2005; 152(3):578-9. · 3.67 Impact Factor
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ABSTRACT: Dendritic cells (DCs) are potent antigen-presenting cells and can induce tumour- or pathogen-specific T cell responses. For adoptive immunotherapy purposes, immature DCs can be generated from adherent monocytes using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin (IL)-4, and further maturation is usually achieved by incubation with tumour necrosis factor (TNF)-alpha. However, TNF-alpha-stimulated DCs produce low levels of IL-12. In this study, we compared the effects of TNF-alpha, interferon (IFN)-gamma, IL-1beta or IFN-gamma + IL-1beta on the phenotypic and functional maturation of DCs. Our results show that IFN-gamma, but not IL-1beta, augmented the surface expression of CD80, CD83 and CD86 molecules without inducing IL-12 production from DCs. However, IL-1beta, but not IFN-gamma, induced IL-12 p40 production by DCs without enhancing phenotypic maturation. When combined, IFN-gamma + IL-1beta treatment profoundly up-regulated the expression of CD80, CD83, CD86 and major histocompatibility complex (MHC) class II antigens. Furthermore, IFN-gamma + IL-1beta-treated DCs produced larger amounts of IL-12 and induced stronger T cell proliferation and IFN-gamma secretion in primary allogeneic mixed lymphocyte reaction (MLR) than did TNF-alpha-treated DCs. Our results show that IFN-gamma + IL-1beta induced human monocyte-derived DCs to differentiate into Th1-prone mature DCs.
Clinical & Experimental Immunology 04/2005; 139(3):476-82. · 3.36 Impact Factor
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T Yamaguchi,
K Ohshima,
K Karube,
T Tutiya,
R Kawano,
H Suefuji,
A Shimizu,
J Nakayama,
J Suzumiya,
Y Moroi, K Urabe,
M Furue,
T Koga,
M Kikuchi
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ABSTRACT: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin.
To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions.
We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration.
The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells.
Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.
British Journal of Dermatology 02/2005; 152(1):76-81. · 3.67 Impact Factor
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H Saeki,
H Iizuka,
Y Mori,
T Akasaka,
H Takagi,
Y Kitajima,
T Tezuka,
T Tanaka,
M Hide,
S Yamamoto,
Y Hirose,
H Kodama, K Urabe,
M Furue,
F Kasagi,
H Torii,
K Nakamura,
E Morita,
Y Tsunemi,
K Tamaki
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ABSTRACT: Although there have been several reports on the prevalence of atopic dermatitis (AD) in Japanese schoolchildren based on questionnaires, there has been no nation-wide study of the frequency of this condition diagnosed by dermatologists in regular health check-ups of schoolchildren.
The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check-ups by dermatologists.
In 2001/2, elementary schoolchildren: first graders (age 6-7 years) and sixth graders (age 11-12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700 x 4 x 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease.
The point prevalence of AD was 11.2% overall (2664 of 23 719) ranging from 7.4% (Iwate) to 15.0% (Fukuoka) in the eight areas. Seventy-four per cent, 24%, 1.6% and 0.3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11.8% vs. 10.5%, P < 0.01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls.
The prevalence of AD in Japanese elementary schoolchildren was about 10%, three-quarters of those being mildly affected. This is the first nation-wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD.
British Journal of Dermatology 02/2005; 152(1):110-4. · 3.67 Impact Factor
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S Saigoh,
A Tashiro,
S Fujita,
M Matsui,
S Shibata,
H Takeshita,
H Duan,
Y Moroi, K Urabe,
T Koga,
M Furue
Dermatology 02/2003; 207(4):410-1. · 2.05 Impact Factor
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ABSTRACT: We describe a unique case of various types of basal cell carcinoma (BCC) associated with basaloid follicular hamartoma (BFH) in a 56-year-old female patient. The lesion consisted of a dark brown and elastic soft nodule and papules within the area of a birthmark on the neck. The lesion was surgically excised. Histological examination of the nodular region revealed aggregations of neoplastic basaloid cells. We diagnosed the nodule as BCC with a racemiform or reticular pattern. In addition, a specimen taken from brownish black papules within the birthmark was found to be composed of anastomosing cords of basaloid cells accompanied by infundibular cystic structures. These features were consistent with an infundibulocystic BCC. In contrast, specimens from a hamartomatous plaque showed distinctive branching strands of basaloid cells that are suggestive of BFH. Therefore, our findings indicate that several types of BCC may develop within a BFH.
Dermatology 02/2003; 207(1):57-60. · 2.05 Impact Factor
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ABSTRACT: Topical steroids are used as the first-line therapy for atopic dermatitis.
To determine the clinical doses of topical steroids for the daily treatment of atopic dermatitis in clinics and to elucidate their adverse effects.
A multicentre retrospective analysis of a series of 1271 patients (210 infants, 546 children, and 515 adolescents and adults) with atopic dermatitis.
Less than 89.5 g, 135 g and 304 g of topical steroid were applied in 90% of the patients in the infant, childhood, and adolescent and adult AD groups, respectively, on the entire body during the 6-month treatment period. The majority of patients were controlled well; however, 7% of infant, 10% of childhood and 19% of adolescent and adult patients remained in a very severe or severe state or experienced exacerbation even though they applied larger amounts of topical steroids. With regard to adverse effects, the incidence of telangiectasia on cheeks tended to increase in patients who had a longer duration of disease and who applied more than 20 g to the face during the 6-month treatment period. The steroid-induced atrophy of the antecubital and popliteal fossae was more frequently observed in males than in females.
Topical steroids are useful for treating atopic dermatitis, but a substantial percentage of patients cannot be satisfactorily treated with topical steroids. For such patients, adjustments of dose and rank of topical steroids and other therapeutic adjuncts are necessary.
British Journal of Dermatology 02/2003; 148(1):128-33. · 3.67 Impact Factor
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ABSTRACT: It has previously been shown that many osteoclast precursors are included in the granulation tissue within the pseudocapsule obtained at revision arthroplasty from hips with osteolysis. In vitro culture of only cells isolated from the granulation tissue has been previously shown to generate many mature osteoclasts.
To investigate the presence or otherwise of supporting cells, similar to stromal cells, which differentiate osteoclasts within the granulation tissue.
Cells isolated from the granulation tissue were cultured alone, and after four weeks fibroblast-like cells (granulation fibroblasts) remained. Rat non-adherent bone marrow cells (NA-BMCs) were co-cultured with the granulation fibroblasts with or without 1alpha,25(OH)2D3 (10(-8) M) or heat treated ROS 17/2.8 cell conditioned medium (ht ROSCM), or both. Multinucleated cells (MNCs), which formed, were assessed by biochemical and functional characterisation of osteoclasts. Receptor activator of NFkappaB ligand (RANKL) was investigated by immunohistochemistry.
Co-culture of NA-BMCs and granulation fibroblasts caused the formation of tartrate resistant acid phosphatase (TRAP) positive MNCs, which had the calcitonin receptor (CTR), the Kat-1 antigen, which is specific to the surface of rat osteoclasts, and the ability to form pits in the presence of both 1alpha,25(OH)2D3 and ht ROSCM or in the presence of just ht ROSCM. RANKL was detected in fibroblast-like cells in the granulation tissue.
These data suggest that granulation fibroblasts support osteoclast differentiation, as do osteoblasts/stromal cells, and may play a part in aseptic loosening.
Annals of the Rheumatic Diseases 03/2002; 61(2):103-9. · 8.73 Impact Factor
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ABSTRACT: Type XI collagen is predominantly found in cartilage. However, expression of the pro-alpha2(XI) collagen gene (COL11A2) has recently been detected in various non-cartilaginous tissues. We identified the differentiation stage at which COL11A2 was expressed in cultured fetal rat calvarial (FRC) cells and in rat femoral fracture calluses in order to investigate the involvement of COL11A2 during bone formation in vitro and in vivo. We also studied the alternative splicing of exons 6-8 in FRC cells and fracture calluses. In FRC cells, mineralized nodules stained with von Kossa stain were observed from day 9 after confluence. COL11A2 was highly expressed on days 0 and 5, but the expression levels were rapidly decreased on day 9 by Northern blot analysis. During rat femoral fracture repair, intramembranous ossification proceeded and newly formed woven bone was observed on the cortex on day 7 after fracture. In situ hybridization showed that COL11A2 signals were detected in osteoblastic cells in the newly formed woven bone. According to the maturation and remodeling of the woven bone into the trabecular bone, the distribution of the signal for COL11A2 mRNA was limited to the superficial osteoblastic cells of the newly formed trabecular bone. These results demonstrated that COL11A2 was expressed in relatively immature osteoblastic cells during bone formation in vitro and in vivo. RT-PCR showed that the shortest band corresponding to mRNA lacking exons 6-8 was clearly detected when using RNA from soft calluses. In contrast, the largest band corresponding to mRNA with exons 6-8 was predominant when using RNA from FRC cells or from hard calluses on days 7 and 14. These results indicate that the splicing pattern of exons 6-8 in osteoblastic cells is different from the pattern in chondrocytes.
Journal of Orthopaedic Research 12/2001; 19(6):1013-20. · 2.81 Impact Factor
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ABSTRACT: We performed an immunohistochemical study to try to determine the cellular source of interleukin-8 (IL-8) in psoriatic skin lesions. IL-8 was positively stained in the vast majority of neutrophils but not in the mononuclear cells, macrophages, or keratinocytes. IL-8-positive neutrophils were seen both in Munro's microabcesses in cases of psoriasis vulgaris and in a small spongiform pustule and much larger macropustules of Kogoj in cases of pustular psoriasis. Some IL-8-positive neutrophils were observed in the upper dermis of pustular psoriasis. The staining was considered to be specific because it could be completely blocked by preabsorption with recombinant IL-8. In addition, stimulation of human neutrophils with lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha) for 18 h induced IL-8 production in vitro. In our study, IL-8 was expressed in the neutrophils of psoriasis, suggesting that neutrophils are one of the sources of IL-8 in psoriasis. The expression of IL-8 and the influx of neutrophils led us to speculate that the IL-8 autocrine and/or paracrine system functions in the formation of the microabcesses and pustules in proriasis.
Journal of Dermatological Science 07/2001; 26(2):119-24. · 3.72 Impact Factor
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ABSTRACT: Rotational alignment of the femoral and tibial components using computed tomography (CT) was evaluated to establish if errors of alignment have a significant effect on patellofemoral complications. From 1987-1990, 54 knees in 39 patients were replaced with the Miller-Galante I knee system. Of these, 10 patients (13 knees) comprised this study. All patients had osteoarthritis. Mean patient age at surgery was 70.3 years. Mean follow-up was 10.3 years. On CT, rotational position of the femoral component relative to the epicondylar axis and the position of the tibial component relative to the tibial tubercle were evaluated. Patellar displacement and patellar tilt angle also were evaluated when the knee was flexed at 30 degrees. Mean rotation of the femoral component was 6.1 degrees of internal rotation (2.7 degrees-11.2 degrees). Mean rotation of the tibial component was 16.7 degrees of internal rotation (2.4 degrees-27.7 degrees). Mean lateral patellar tilt angle was 2.9 degrees (-6.0 degrees-11.9 degrees), and mean lateral displacement was 2.7 mm (-3.2-8.9 mm). Rotational position of both the femoral and tibial components showed a statistically significant correlation with the patellar tilt angle. This study showed the internally rotated femoral and tibial component were related to the patellar maltracking. This malalignment of the components, as well as nonanatomical patellar groove and metal-backed patellar component, could be one of the causes of the patellofemoral complications with the Miller-Galante I knee.
The American journal of knee surgery 02/2001; 14(3):152-6.
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ABSTRACT: We developed a new patella-cutting guide that simplifies proper alignment and enables resection of the correct thickness of bone. This guide consists of a central shaft, two support frames, and a ring. The ring consists of upper and lower disks, with a slot between the disks. The central shaft and the lower disk have holes for fixation pins. The distance from the distal end of the central shaft to the lowest level of the slot is 8 mm. Bone of the same thickness as that of the patellar component can be automatically resected using this guide. A feeler gauge is inserted through the slot, and the periarticular region is felt. This procedure enables the guide to be set at the correct angulation. A laboratory study using fresh-frozen cadaver patella specimens and a clinical study showed that proper alignment and proper resection were achieved using this guide.
The American journal of knee surgery 02/2001; 14(4):227-31.
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ABSTRACT: Bowen's disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology. Objectives To evaluate the relationship between the cytological properties of the tumour cells in BD and the host immune response.
We examined the expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 antigen, and the number of mitotic cells, together with the number of intratumoral and dermal infiltrating CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen (CLA)+ cells in 18 cases of genital BD.
When compared with normal genital skin (n = 10), there was a significantly higher number of mitotic cells as well as higher expression of p53+, PCNA+ and Ki67+ cells in BD. There was significant mutual correlation between CD3+, CD4+ and CD68+ cells in the tumoral epidermis. The number of CD1a+ Langerhans cells significantly decreased in BD epidermis; however, dermal CD1a+ cells were increased. Interestingly, numbers of dermal CD1a+ cells significantly correlated with those of intratumoral CD3+, CD4+ and CD68+ cells. In situ hybridization for human papillomavirus (HPV) demonstrated that HPV-infected BD had significantly less infiltration of intratumoral CD3+ cells and CLA+ cells.
The present data suggest that dermal CD1a+ cells may participate in the immune surveillance and that HPV infection may interfere with the intratumoral infiltration of CLA+ cells in BD.
British Journal of Dermatology 01/2001; 143(6):1211-6. · 3.67 Impact Factor
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ABSTRACT: Acquired generalized hypohidrosis/anhidrosis is a rare condition of unknown pathogenesis, while idiopathic cholinergic urticaria is relatively common. We report the case of a 19-year-old male with cholinergic urticaria and acquired generalized hypohidrosis, and review previously published similar cases of this association.
British Journal of Dermatology 12/2000; 143(5):1064-6. · 3.67 Impact Factor
