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1.
Cancers (Basel) ; 15(19)2023 Oct 05.
Article En | MEDLINE | ID: mdl-37835554

Synovial sarcomas are rare and highly aggressive soft-tissue sarcomas, primarily affecting adolescents and young adults aged 15-40 years. These tumors typically arise in the deep soft tissues, often near the large joints of the extremities. While the radiological features of these tumors are not definitely indicative, the presence of calcification in a soft-tissue mass (occurring in 30% of cases), adjacent to a joint, strongly suggests the diagnosis. Cross-sectional imaging characteristics play a crucial role in diagnosing synovial sarcomas. They often reveal significant characteristics such as multilobulation and pronounced heterogeneity (forming the "triple sign"), in addition to features like hemorrhage and fluid-fluid levels with septa (resulting in the "bowl of grapes" appearance). Nevertheless, the existence of non-aggressive features, such as gradual growth (with an average time to diagnosis of 2-4 years) and small size (initially measuring < 5 cm) with well-defined margins, can lead to an initial misclassification as a benign lesion. Larger size, older age, and higher tumor grade have been established as adverse predictive indicators for both local disease recurrence and the occurrence of metastasis. Recently, the prognostic importance of CT and MRI characteristics for synovial sarcomas was elucidated. These include factors like the absence of calcification, the presence of cystic components, hemorrhage, the bowl of grape sign, the triple sign, and intercompartmental extension. Wide surgical excision remains the established approach for definitive treatment. Gaining insight into and identifying the diverse range of presentations of synovial sarcomas, which correlate with the prognosis, might be helpful in achieving the optimal patient management.

2.
Ann Dermatol ; 33(6): 568-571, 2021 Dec.
Article En | MEDLINE | ID: mdl-34858009

Friction melanosis (FM) is an acquired pigmented disease that is caused by recurrent mechanical stress. There is no previous report explaining the presence of tiny brown-colored particles confined to the corneal layer. We describe a case of a rare form of FM of the finger that showed a relatively transient clinical course. A 17-year-old Korean female presented with a 5-month history of an asymptomatic localized hyperpigmented patch on the tip of the right index finger. The dermoscopic examination revealed homogenous globular pattern, which favored pigmentation over hemorrhage. Histopathologically, hyperkeratosis and acanthosis with lymphohistiocytic infiltration of the superficial dermis were noted on hematoxylin and eosin staining; however, there was neither a definite increase in melanophages in the upper dermis nor melanocytic proliferation in the basal layer. Per high-power field, multiple brown-colored tiny particles were scattered in the corneal layer. The particles were not dyed by Fontana-Masson stain, iron stain, and S-100. We questioned the patient about the presence of irritation and found that she had bought new shoes at the time of the onset. She was habituated to placing her fingers in her shoes while wearing them because they were slightly tight. The lesion disappeared spontaneously a week after the cause of friction was eliminated. Altogether, we encountered a rare form of FM that occurred in a rare location with a transient clinical course. Further cases on pigmentation restricted to finger tips might reveal the origin of the particles.

3.
Ann Dermatol ; 33(2): 178-181, 2021 Apr.
Article En | MEDLINE | ID: mdl-33935460

A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL.

4.
Ann Dermatol ; 32(2): 146-150, 2020 Apr.
Article En | MEDLINE | ID: mdl-33911726

Solitary fibrous tumor (SFT) is a relatively uncommon mesenchymal neoplasm that usually arises in the pleura, but also has been reported in numerous extrapleural locations, including cutaneous site. The skin lesion presents as a circumscribed nodule or tumor, mainly on the head and neck. A 41-year-old male presented with 6 months history of nail lesion without symptom on the left third finger. The lesion is slightly yellowish discoloration with subungual erythematous nodule and distal onycholysis. Biopsy specimen from the nail lesion showed the spindle cells form patternless pattern with hypercellular and hypocellular area. And small blood vessels and dilated vascular spaces were present. The result of special stain for specimen showed that positive for CD34, Bcl-2, and CD99 but negative for S-100, FactorXIIIa, and smooth muscle action. Recognition of this uncommon location of SFT is important because of possible confusion with other subungual tumors, including glomus tumor, fibroma and other fibrohistiocytic tumors like dermatofibrosarcoma protuberans, superficial acral fibromyxoma and cellular digital fibroma. Here in, we report a case of SFT of subungual region. We think this case is interesting because of uncommon location and may be helpful to more understand the character of this disease.

5.
Ann Dermatol ; 32(4): 327-330, 2020 Aug.
Article En | MEDLINE | ID: mdl-33911760

A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow-band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient.

6.
Plast Reconstr Surg ; 144(4): 659e-668e, 2019 10.
Article En | MEDLINE | ID: mdl-31568312

BACKGROUND: Botulinum toxin type A (BTxA) injection is effective for surgical scar prevention. Although some studies have aimed to confirm the efficacy of BTxA injection at different time points, none has been conducted to determine the most appropriate timing of injection for scar management. The authors predicted that the injection of BTxA at different times during the wound healing process would cause differing scar quality improvement and clarify unknown molecular mechanisms. METHODS: The study included adults who underwent thyroidectomy. All patients received paralesional BTxA injections on the day of the surgery on either the right or left side of the operative site. The same dose was injected on the noninjected side by means of the same method after 2 weeks. At 2, 4, 12, and 24 weeks postoperatively, the modified Stony Brook Scar Evaluation Scale, visual analogue scale, and erythema index were used for objective, subjective, and quantitative evaluations of the scar. At week 24 postoperatively, a quantitative scar assessment was performed with respect to the erythema index, skin elasticity, melanin index, and friction. RESULTS: On objective evaluation of the scar and patient satisfaction at 24 weeks postoperatively, the operation-day injection side showed better outcomes than the 2-week-postoperative injection side. These differences were significant from postoperative week 4. In the final quantitative scar assessment at postoperative week 24, significant improvements were observed in the erythema index and skin elasticity. CONCLUSION: These results suggest that immediate postoperative BTxA injection is more effective for thyroidectomy scar management in terms of erythema, skin elasticity, and patient satisfaction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.


Botulinum Toxins, Type A/administration & dosage , Cicatrix/etiology , Cicatrix/prevention & control , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Thyroidectomy/adverse effects , Wound Healing/drug effects , Adult , Aged , Female , Humans , Injections, Intralesional , Male , Middle Aged , Prospective Studies , Time Factors
7.
J Dermatol ; 46(11): 978-984, 2019 Nov.
Article En | MEDLINE | ID: mdl-31489692

Distinguishing between Malassezia folliculitis (Pityrosporum folliculitis [P. folliculitis]) and acneiform eruption, based on clinicopathological features, is challenging for clinicians. In the literature, the histopathological differences between P. folliculitis and acneiform eruption lesions have been poorly described. We aimed to determine the clinicopathologic distinctions between P. folliculitis and acneiform eruption by retrospectively analyzing the histology of hematoxylin and eosin stained tissue sections obtained from 52 patients diagnosed with these lesions. The presence of fungal spores in the follicular lumen was most consistent with a P. folliculitis diagnosis (P < 0.001). However, intrafollicular inflammation (P = 0.009), irregular patterns of keratin plugging (P = 0.008), and nuclear dust in the follicular lumen (P < 0.001) favored an acneiform eruption diagnosis. These intrafollicular characteristics and inflammatory differences are believed to be caused by necrotic keratinocytes that lead to vacuolar changes in the follicular wall (P = 0.013). We did not observe any difference between P. folliculitis and acneiform eruption lesions in terms of perifollicular inflammatory cell infiltration. Our study demonstrated that significant differences exist between P. folliculitis and acneiform eruption lesions relative to the presence of necrotic keratinocytes in the follicular wall, intrafollicular characteristics, and inflammatory cell infiltrations. Necrotic keratinocytes are believed to have a key role in these differences. These findings may contribute to an improved understanding of the pathogenesis and differential diagnosis of P. folliculitis and acneiform eruption.


Acneiform Eruptions/diagnosis , Folliculitis/diagnosis , Folliculitis/microbiology , Malassezia/isolation & purification , Acneiform Eruptions/pathology , Adult , Diagnosis, Differential , Female , Folliculitis/pathology , Humans , Male
8.
Arch Dermatol Res ; 311(10): 807-814, 2019 Dec.
Article En | MEDLINE | ID: mdl-31501922

Hypertrophic scar is a dermal fibroproliferative disease characterized by the overproduction and deposition of extracellular matrix, and the hyperproliferation and enhanced angiogenesis of fibroblasts, along with their enhanced differentiation to myofibroblasts. Botulinum toxin type A shows potential for prevention of hypertrophic scar formation; however, its effectiveness in attenuating skin fibrosis and the related mechanism are unclear. In this study, human scar fibroblasts were cultured and stimulated with botulinum toxin type A, and the changes in fibroblast proliferation, migration, and protein expression of pro-fibrotic factors were evaluated with colorimetric, scratch, and enzyme-linked immunosorbent assays and western blotting, respectively. Botulinum toxin type A treatment decreased the proliferation and migration of human scar fibroblasts compared with those of untreated controls. Protein expression levels of pro-fibrotic factors (transforming growth factor ß1, interleukin-6, and connective tissue growth factor) were also inhibited by botulinum toxin type A, whereas the JNK phosphorylation level was increased. Activation of the JNK pathway demonstrated the inhibitory effects of the toxin on human scar fibroblast proliferation and production of pro-fibrotic factors, suggesting that the suppressive effects of botulinum toxin type A are closely associated with JNK phosphorylation. Overall, this study showed that botulinum toxin type A has a suppressive effect on extracellular matrix production and scar-related factors in human scar fibroblasts in vitro, and that regulation of JNK signaling plays an important role in this process. Our results provide a theoretical basis, at the cellular level, for the therapeutic use of botulinum toxin type A.


Botulinum Toxins, Type A/pharmacology , Cicatrix, Hypertrophic/drug therapy , Fibroblasts/drug effects , MAP Kinase Signaling System/drug effects , Botulinum Toxins, Type A/therapeutic use , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Cicatrix, Hypertrophic/pathology , Cicatrix, Hypertrophic/surgery , Extracellular Matrix/drug effects , Fibroblasts/pathology , Humans , Interleukin-6/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Phosphorylation/drug effects , Primary Cell Culture , Transforming Growth Factor beta1/metabolism
9.
Ann Dermatol ; 31(1): 70-74, 2019 Feb.
Article En | MEDLINE | ID: mdl-33911542

Patients with atopic dermatitis have high rates of skin surface colonization of Staphylococcus aureus. At the same time, S. aureus is the major causative organism in infective endocarditis, approximately accounting for 30%~50% cases of infective endocarditis. A 22-year-old male with severe atopic dermatitis presented with fever and myalgia. He was diagnosed with active infective endocarditis causing multiple cerebral infarction, splenic infarction, and septic shoulder requiring synovectomy. Blood culture proved methicillinsensitive Staphylococcus aureus bacteremia, and the culture from the skin revealed same bacteria. After treated with intravenous antibiotics for 6 weeks, patient was improved. Another 42-year-old female with severe atopic dermatitis who presented with fever and chilling was hospitalized due to acute infective endocarditis. She also had left flank pain and visual disturbance, due to splenic infarction and acute cerebral infarction, respectively. As blood culture revealed methicillin-sensitive Staphylococcus aureus bacteremia, she treated with intravenous antibiotics for 6 weeks. The route of entry of two patients was attributed to the patient eczematous scratching lesion of poorly controlled atopic dermatitis. Infective endocarditis can result in the context of acute deterioration of atopic dermatitis. Dermatologists need to pay attention to this risk and actively manage such conditions in order to decrease the risk of infective endocarditis arising from skin lesions in atopic patients. For these reasons, we herein report two cases of infective endocarditis in patients with atopic dermatitis.

10.
J Cosmet Dermatol ; 18(4): 1105-1112, 2019 Aug.
Article En | MEDLINE | ID: mdl-30280483

BACKGROUND: Platelet-rich plasma (PRP) is a blood fraction that contains high concentrations of several growth factors. PRP has been recently used in skin wound healing and rejuvenation. However, the precise molecular mechanisms underlying PRP-induced wound healing are unknown. AIMS: This study aimed to evaluate the effects of PRP on extracellular matrix remodeling, which requires the activation of dermal fibroblasts. METHODS: Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, and Western blotting were performed on PRP-treated human skin fibroblasts. RESULTS: Platelet numbers were enhanced by 4.6-fold in PRP compared to that in whole blood. PRP stimulated the proliferation and migration of human dermal fibroblasts and increased the expression of human procollagen I alpha 1, elastin, MMP-1, and MMP-2 in human dermal fibroblasts. PRP-treated human dermal fibroblasts also showed a dramatic reduction in the phosphorylation of c-Jun N-terminal kinase (JNK), whereas total JNK levels were not significantly reduced. CONCLUSIONS: Collectively, PRP induced increased expression of type I collagen, elastin, MMP-1, and MMP-2, thereby accelerating wound healing. Our findings reveal basic mechanisms underlying PRP-mediated tissue remodeling. Thus, these results could be exploited for clinical dermatology and skin rejuvenation.


Dermis/drug effects , Fibroblasts/drug effects , Platelet-Rich Plasma , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Dermis/cytology , Dermis/metabolism , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Fibroblasts/metabolism , Humans , Primary Cell Culture , Rejuvenation , Skin Aging/drug effects , Wound Healing/drug effects
12.
Dermatol Surg ; 44(9): 1209-1215, 2018 Sep.
Article En | MEDLINE | ID: mdl-29746429

BACKGROUND: Dual-frequency ultrasound (DFU) has emerged as a new treatment modality for improving inflammatory skin disorders. Although there have been few pilot studies, there are a limited number of studies that investigated efficacy of DFU on refractory rosacea. OBJECTIVE: This study investigated the effect of DFU on patients with refractory rosacea. MATERIALS AND METHODS: The authors retrospectively analyzed medical records of 42 patients with refractory rosacea (erythematotelangiectatic rosacea [ETR], n = 26; papulopustular rosacea [PPR], n = 14, mixed, n = 2). The patients were treated with DFU twice per week for the 1st week, and then once per week thereafter. Efficacy was assessed using erythema index (EI), transepithelial water loss (TEWL), and patient self-assessment (PSA). RESULTS: Treatment with DFU resulted in significant decrease in EI, TEWL, and PSA. No significant difference was noted between ETR and PPR. CONCLUSION: Application of DFU in patients with refractory rosacea resulted in improvement in persistent erythema, barrier dysfunction, and patient-reported symptoms. Dual-frequency ultrasound may be an additional treatment option for rosacea that is resistant to other treatments.


Rosacea/therapy , Ultrasonic Therapy , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Rosacea/pathology , Time Factors , Treatment Outcome , Young Adult
13.
Ann Dermatol ; 30(2): 136-142, 2018 Apr.
Article En | MEDLINE | ID: mdl-29606809

BACKGROUND: Rosacea is a chronic inflammatory disease characterized by centrofacial erythema. Excess cathelicidin is suggested to be important to the pathophysiology of the disease. Recently, presence of a vitamin D response element was revealed in the cathelicidin gene promoter. OBJECTIVE: The aim of this study was to determine whether vitamin D and cathelicidin are associated with rosacea, both serologically and histopathologically. METHODS: Subjects with rosacea and without chronic skin disorders were enrolled in the patient and control groups, respectively. Serum 25-hydroxy-vitamin D and cathelicidin levels were measured. Tissue expression of cathelicidin and vitamin D receptor were measured with immunostaining-intensity-distribution index. RESULTS: The mean serum 25-hydroxyvitamin D level of patients with rosacea was 12.18±5.65 ng/ml, which is lower than that of the controls (17.41±6.75 ng/ml). Mean serum cathelicidin levels in patients with rosacea and the controls were 85.0±26.1 ng/ml and 55.0±23.3 ng/ml, respectively. Cathelicidin expression in rosacea tissue was significantly higher than that in control tissue (5.21 vs. 4.03). No significant difference was observed in vitamin D receptor expression. CONCLUSION: Higher cathelicidin expression in rosacea supports the hypothesis that an abnormal inflammatory response of the innate immune system is important in pathogenesis of rosacea, but the role of high cathelicidin serum levels is complicated. Serum vitamin D was lower in patients with rosacea, although serum cathelicidin was higher than that of the controls. This suggests that the role of vitamin D level in the pathogenesis of rosacea merits further investigation.

14.
J Cutan Med Surg ; 22(3): 285-289, 2018.
Article En | MEDLINE | ID: mdl-29528750

BACKGROUND: Diphenylcyclopropenone (DPCP) immunotherapy for viral warts has been used for many years, but no studies have analyzed the treatment effects of DPCP alone, without the use of conventional therapy before immunotherapy. OBJECTIVES: We evaluated clinical efficacy of DPCP monotherapy compared to cryotherapy and pulsed dye laser (PDL) therapy. We also assessed the impact of initial sensitization on clinical response. METHODS: We retrospectively analyzed the medical records of 250 patients with multiple viral warts between January 2008 and December 2015. RESULTS: The DPCP-only group (n = 43) showed a lower clinical response (75.6%) than the cryotherapy-only group (n = 171, 89.8%, P < .01) and PDL-only group (n = 36, 90.3%, P < .01). The positive clinical response was 76.3% (119/156) in the successful sensitization group (n = 21) and 74.4% in the failed sensitization group ( P = .870). CONCLUSIONS: DPCP monotherapy has a lower clinical response than conventional therapy. Initial sensitization to DPCP does not predict a failed response with continued immunotherapy for viral warts.


Cyclopropanes/therapeutic use , Dermatologic Agents/therapeutic use , Immunotherapy , Warts/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cryotherapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome , Young Adult
15.
J Cosmet Laser Ther ; 20(5): 260-264, 2018 Oct.
Article En | MEDLINE | ID: mdl-29388843

BACKGROUND: Rosacea is characterized by erythema on face, especially erythema and linear telangiectasia on the nose. Currently, various vascular lasers are used for treatment, and among them, are long-pulsed Nd:YAG(LPNY) and pulsed dye laser (PDL). OBJECTIVES: This study compared the efficacy of LPNY and PDL in treating rosacea-associated nasal telangiectasia. METHODS: Patients with rosacea who showed erythema and telangiectasia on the nose were included. Each patient was treated with PDL on the left side of the nasal bridge, and LPNY on the right side, three times with 4-week intervals. At the end of the treatment, two independent dermatologists evaluated overall treatment response compared with baseline. RESULTS: The physician's assessment of treatment concluded that good improvement was seen in six PDL and seven LPNY patients, and excellent improvement five PDL and four LPNY patients. There was no significant difference (p = 0.62, 95%CI) between the groups. Overall improvement was similar; however, LPNY induced a greater response in thick, dilated vessels, while erythema with mild telangiectasia was more responsive to PDL. CONCLUSION: Both LPNY and PDL are effective in treating rosacea-associated nasal telangiectasia. If LPNY is used properly to avoid side effects with careful consideration, it can also be used as a good modality.


Lasers, Dye/therapeutic use , Lasers, Solid-State/therapeutic use , Low-Level Light Therapy/instrumentation , Rosacea/radiotherapy , Telangiectasis/radiotherapy , Adult , Aged , Erythema/etiology , Erythema/radiotherapy , Facial Dermatoses/etiology , Facial Dermatoses/radiotherapy , Female , Humans , Male , Middle Aged , Nose , Rosacea/complications , Telangiectasis/etiology , Treatment Outcome
16.
Ann Dermatol ; 30(6): 662-667, 2018 Dec.
Article En | MEDLINE | ID: mdl-33911505

BACKGROUND: Recently, the number of domestic pets has increased. As a consequence, sensitization to animal allergens, such as cat or dog allergens, has become a problem. OBJECTIVE: We studied the annual trends of sensitization to cats or dogs, and the characteristics of the patients. METHODS: We retrospectively analyzed the medical records of 7,469 patients who visited a dermatology clinic and underwent an allergic profile test, from January 2011 to December 2015. Specific immunoglobulin E (IgE) levels to cat or dog antibody greater than 3.50 IU/ml were regarded as positive results. RESULTS: In all, 274 patients showed significant increase in levels of specific IgE antibody to dog, and 307 revealed increase in levels of of specific IgE antibody to cat. The prevalence of these specific IgEs increased from 2011 to 2015. Independent risks for sensitization to cat allergens were sensitization to dog, but not to house dust, Dermatophagoides pteronyssinus, and D. farinae. Independent risks for sensitization to dog allergens were sensitization to cat, but not to house dust, D. pteronyssinus, and D. farinae. Total IgE level was not related to specific IgE level against either cats or dogs. CONCLUSION: In conclusion, the prevalence of sensitization to cat or dog has increased. Sensitization to cat or dog is related to each other, but is irrelevant to the total IgE level.

17.
Ann Dermatol ; 29(6): 776-778, 2017 Dec.
Article En | MEDLINE | ID: mdl-29200768

A 4-month-old infant presented with asymptomatic soft nodules on his right forearm, which had developed since birth. On the suspicion of nevus lipomatosus superficialis (NLS), biopsy was performed. Histopathologic findings showed monomorphic polygonal cells with abundant granular cytoplasm. Immunohistochemical stains for CD68 and vimentin were strongly positive, but were negative for S-100 protein. Based on the pathologic findings, the patient was diagnosed as non-neural granular cell tumor (NN-GCT). GCT can be divided into conventional and non-neural GCT by immunoreactivity for S-100 protein. NN-GCT is typically manifested as a well-circumscribed, papulo-nodular dermal mass, and is known to occur in a younger group than does in conventional GCT, but is rare among children. To our knowledge, there have been no case reports of NN-GCT which appeared at birth and presented as grouped nodules. Therefore, we report this interesting case of congenital NN-GCT clinically mimicking NLS.

19.
Toxicology ; 387: 1-9, 2017 07 15.
Article En | MEDLINE | ID: mdl-28645575

Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an in vitro model system for assessment of drug-induced as well as immune-mediated hepatotoxicity.


Acetaminophen/toxicity , Analgesics, Non-Narcotic/toxicity , Biological Assay , Cell Differentiation , Chemical and Drug Induced Liver Injury/etiology , Embryonic Stem Cells/drug effects , Hepatocytes/drug effects , Hypoglycemic Agents/toxicity , Thiazolidinediones/toxicity , Toxicity Tests/methods , Cell Survival/drug effects , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cytokines/immunology , Cytokines/metabolism , Embryonic Stem Cells/immunology , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/pathology , Hepatocytes/immunology , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Inflammation Mediators/immunology , Inflammation Mediators/metabolism , Jurkat Cells , Phenotype , Risk Assessment
20.
Eur J Dermatol ; 27(3): 275-280, 2017 Jun 01.
Article En | MEDLINE | ID: mdl-28524064

Longitudinal melanonychia is not frequently observed in children, and few studies exist on longitudinal melanonychia in paediatric patients, especially in Asian populations. We aimed to evaluate the clinical and histological findings of longitudinal melanonychia in Korean paediatric patients. A retrospective review of paediatric patients (≤18 years old) with longitudinal melanonychia who underwent nail biopsy between January 2010 and October 2015 was performed. Of a total of 21 patients with longitudinal melanonychia, there were 10 cases of functional melanonychia, eight of lentigo, and three of nevus, as determined by microscopic examination. Mild nuclear atypia was found in four cases, as well as a low degree of pagetoid spread in one case. No patient was diagnosed with melanoma. During the follow-up period, no signs of malignancy were noticed and one patient with nail matrix nevus showed complete spontaneous regression of the pigmented band. Clinical and histological features, generally accepted as signs suggestive of melanoma in adults, were more readily observed in benign conditions in children.


Asian People , Melanosis/pathology , Nail Diseases/pathology , Adolescent , Biopsy , Child , Child, Preschool , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Infant , Lentigo/pathology , Male , Melanoma/diagnosis , Nevus, Pigmented/pathology , Remission, Spontaneous , Retrospective Studies , Skin Neoplasms/diagnosis
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