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Apoptotic Keratinocytes (apoptotic + keratinocyte)

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Medical Sciences	83%

Selected Abstracts

Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis

BRITISH JOURNAL OF DERMATOLOGY, Issue 5 2004
A-Y. Lee
Summary Background, Vitiligo may develop following minor physical trauma. However, in autologous epidermal grafting, depigmentation of the donor (normally pigmented) site from a suction blister is rare, even in cases displaying failure of repigmentation at the recipient (depigmented) site. Objectives, To examine whether the suction procedure is more likely to damage keratinocytes in the depigmented than in the normally pigmented epidermis of vitiligo, and to determine what kind of damage occurs to the keratinocytes. Methods, Paired roofs of suction blisters from five patients with generalized vitiligo, five with localized and seven with segmental type, were used for the study. Multiple new lesions developed in two of the five patients with the generalized type. Apoptosis of keratinocytes in the epidermis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labelling (TUNEL) staining, with immunohistochemistry for Bax and active caspase 3. Expression of Bcl-2, Bax, FLIP and p53, activation of caspases 3, 8 and 9, and cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) in the epidermis were analysed by Western blotting in four patients with each type. Results, Apoptotic keratinocytes, which stained with TUNEL and anti-Bax and antiactive caspase 3 antibodies, were scattered in the blistered epidermis, mainly in the lower portions. The depigmented epidermis displayed significantly more apoptotic keratinocytes than the normally pigmented epidermis. The numerical difference between the paired epidermides was related to the disease activity and not to the type of lesions. The number of apoptotic keratinocytes in the normally pigmented epidermis was as high as that in the depigmented epidermis in the two patients with active generalized type vitiligo. Expression of Bax and p53 in the depigmented epidermis was higher than in the normally pigmented epidermis, whereas expression of FLIP was lower. In addition, the activation of caspases 3, 8 and 9, and cleavage of PARP, were increased in the depigmented compared with the normally pigmented epidermis. The degree of difference in expression and activation was parallel to the results of the TUNEL assay. Conclusions, The keratinocytes in the depigmented compared with the normally pigmented epidermis of vitiligo may become apoptotic more easily after suction. [source]

Green tea extract reduces induction of p53 and apoptosis in UVB-irradiated human skin independent of transcriptional controls

EXPERIMENTAL DERMATOLOGY, Issue 1 2009
Christian D. Mnich
Abstract:, Ultraviolet (UV) irradiation plays a pivotal role in human skin carcinongenesis. Preclinically, systemically and topically applied green tea extract (GTE) has shown reduction of UV-induced (i) erythema, (ii) DNA damage, (iii) formation of radical oxygen species and (iv) downregulation of numerous factors related to apoptosis, inflammation, differentiation and carcinogenesis. In humans, topical GTE has so far only been tested in limited studies, with usually very high GTE concentrations and over short periods of time. Both chemical stability of GTE and staining properties of highly concentrated green tea polyphenols limit the usability of highly concentrated green tea extracts in cosmetic products. The present study tested the utility of stabilized low-dose GTE as photochemopreventive agents under everyday conditions. We irradiated with up to 100 mJ/cm2 of UVB light skin patches which were pretreated with either OM24® -containing lotion or a placebo lotion. Biopsies were taken from both irradiated and un-irradiated skin for both immunohistochemistry and DNA microarray analysis. We found that while OM24® treatment did not significantly affect UV-induced erythema and thymidine dimer formation, OM24® treatment significantly reduced UV-induced p53 expression in keratinocytes. We also found that OM24® treatment significantly reduced the number of apoptotic keratinocytes (sunburn cells and TUNEL-positive cells). Carefully controlled DNA microarray analyses showed that OM24® treatment does not induce off-target changes in gene expression, reducing the likelihood of unwanted side-effects. Topical GTE (OM24®) reduces UVB-mediated epithelial damage already at low, cosmetically usable concentrations, without tachyphylaxis over 5 weeks, suggesting GTE as suitable everyday photochemopreventive agents. [source]

Lichenoid nail changes as sole external manifestation of graft vs. host disease

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2002
Sara Isabel Palencia MD
A 56-year-old-man who had refractory anemia with an excess of blasts underwent an allogeneic peripheral blood stem cell transplantation (PBSCT) from his brother after preparation with melphalan and fludarabin. He received GvHD (graft-vs.-host disease) prophylaxis with cyclosporine from day ,1 at a daily dose of 5 mg/kg of body weight. The daily dosage was tapered gradually from day +20. On post-PBSCT day 68 he developed acute cutaneous GvHD grade 3 and acute gastrointestinal GvHD grade 2,3, which was resolved with a daily dose of 1 mg/kg of body weight of prednisone. The patient was discharged in good clinical condition and without signs of GvHD, and he started tapering his immunosuppressive treatment. By day 160 he developed oral lichen planus-like changes, with several reticulate white lesions on the oral mucosa. A biopsy specimen was microscopically consistent with lichenoid GvHD (Fig. 1). By day 150 after PBSCT, when he was being treated with CsA 100 mg once daily and prednisone 10 mg once daily, his fingernails started to grow abnormally and gradually became dystrophic and painful. Two months later his toenails became similarly affected. Although affecting all finger and toe nails, the lesions were especially important in both thumbs. Physical examination revealed multiple findings on his nails (Fig. 2): thickening, fragility, onycholysis, longitudinal striations, and even pterygium. The micological cultures were negative. A biopsy specimen showed an sparse papillary dermis lymphoid infiltrate with focal exocytosis and presence of isolated multiple necrotic keratinocytes (Fig. 3). These findings were interpreted as a lichenoid GvHD with oral and nail involvement. The patient did not have other associated cutaneous lesions. He did not develop signs or symptoms consistent with hepatic GvHD. In May 2000 thalidomide was added to the immunosuppressive therapy, at a daily dose from 100 to 300 mg according to tolerance (constipation, sedation, ,). The lesions on the oral mucous showed a substantial improvement, but the nail changes remained more or less stable. Thalidomide was discontinued after 7 months because the patient displayed numbness and tingling in the hands and feet consistent with a peripheral neuropathy. Twenty days later he stopped taking thalidomide and the oral lichenoid lesions worsened, resulting in difficulty in eating. He also developed periungueal erythema, swelling and intense pain after minimal trauma. The daily dose of prednisone increased to 20,30 mg with moderate improvement. However, the dose could not be increased because of the secondary immunosuppressive effects. Twenty-three months post-PBSCT the patient remains with intense oral and nail lichenoid lesions. Figure Figure 1 . Oral mucosa with a lichenoid hiperplasia and a band-like lymphoid infiltrate. Note the basal lymphocytosis with isolated necrotic keratinocytes Figure 2. Lichenoid graft-vs.-host disease showing marked nail involvement with a ridge in the midline Figure 3. Panoramic view of the nail epithelium. Dermal lymphocytes with basal exocytosis and apoptotic keratinocytes (arrow) are evident [source]

Inverse Relationship Between Increased Apoptosis and Decreased Skin Cancer in UV-irradiated CD1d -/- Mice,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2005
Yasuhiro Matsumura
ABSTRACT We previously demonstrated that CD1d knockout mice were resistant to ultraviolet (UV)-induced immunosuppression. Because immune suppression is a critical factor in the development of UV-induced skin cancers, we investigated the response of wild type (WT) and CD1d -/- mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d -/- mice developed skin tumors. To investigate the mechanisms involved in the resistance of CD1d -/- mice to UV-induced carcinogenesis, we determined the time course and kinetics of keratinocyte cell death after UV irradiation. After acute UV exposure, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)-positive keratinocytes were eliminated from the skin of WT mice by 72 h post-UV, but they still persisted until 96 h in CD1d -/- mice. The kinetics of p53 protein expression closely followed the kinetics of apoptotic cell death. Chronic UV irradiation resulted in induction of a significantly higher number of apoptotic keratinocytes in CD1d -/- than WT mice. In addition, epidermis and dermis from chronically UV-irradiated CD1d -/- mice harbored significantly fewer p53 mutations than WT mice. These results indicate that the resistance of CD1d -/- mice to UV carcinogenesis may be due to increased cell death and elimination of keratinocytes and fibroblasts containing DNA damage and p53 mutations. [source]

Erythema multiforme, Stevens,Johnson syndrome and toxic epidermal necrolysis: Frozen-section diagnosis

THE JOURNAL OF DERMATOLOGY, Issue 5 2010
Hiroomi HOSAKA
Abstract Stevens,Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) may be fatal. Although classified by body surface area skin detachment, initial stages of both may present with erythema multiforme (EM)-like lesions. To diagnose and predict disease activity adequately as early as possible for patients revealing EM-like lesions, we performed frozen-section diagnosis. Thirty-five patients clinically diagnosed as EM, SJS or TEN were biopsied to diagnose and predict disease progression within the initial-visit day. Half of a histological section taken from a lesion was snap-frozen and immediately cryostat-sectioned, acetone-fixed and stained with hematoxylin,eosin. Specimens were examined with light microscopy for presence of epidermal necrosis. A section from unaffected sites was also examined for 11 patients. Specimens were examined with light microscopy for presence of graft-versus-host reaction (GVHR)-like findings: apoptotic keratinocytes and satellite cell necrosis. Epidermal necrosis was seen in nine patients. Initial diagnosis of the nine was one of overlap SJS-TEN, four of SJS and four of EM, and final diagnosis of those was one of TEN, one of overlap SJS,TEN, four of SJS and three of EM. Dissociation between initial and final diagnosis was seen in three cases. GVHR-like findings in the epidermis were observed in two patients finally diagnosed as overlap SJS,TEN and TEN. Frozen sections are useful not only to make a diagnosis of erythema multiforme but to assess a potential to exhibit more aggressive clinical behaviors (SJS or TEN). [source]

Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis