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Abstract: Background: Recent studies showed that Wnt signaling through the β-catenin pathway (canonical Wnt signaling) act on mouse dermal papilla cells (DPCs) enabling hair follicles to keep growing. Objective: To investigate whether human DPCs respond to canonical Wnt signaling and, if so, to identify target genes of Wnt/β-catenin pathway. Methods: Cultured human DPCs were transiently transfected with the β-catenin responsive TCF reporter plasmid (pTopflash) and corresponding negative control reporter (pFopflash) to assess the activity of β-catenin signaling by Wnt3a (one of the canonical Wnts). Immunofluorescence staining was also performed to localize β-catenin in the presence or absence of Wnt3a. Microarray was carried out using Affymetrix gene chips. RT-PCR analysis and immunoblot were employed to verify microarray data. Cyclic AMP (cAMP) levels were measured using EIA assay after Wnt3a and PGE2 treatment in DPCs. Results: Wnt3a significantly stimulated the transcriptional activity of pTopflash but not pFopflash. In line with this, we identified a number of genes that are regulated by Wnt3a. Some of the differently expressed genes including EP2 were confirmed by RT-PCR analysis. Immunoblot further confirmed that EP2 protein is indeed increased by Wnt3a. DPCs pretreated with Wnt3a showed higher responsiveness to PGE2 as measured by cAMP levels. Conclusions: Elucidation of the role of Wnt3a-regulated genes identified in this study including EP2 would help our understanding of hair-induction and maintenance of anagen phase. [Copyright &y& Elsevier]

Background: Various types of follicular trauma occur during follicular unit excision (FUE). However, the effects of different types of follicular injury on graft survival have not been reported., Objective: This study was performed to evaluate the differences in hair follicle survival by the type of follicular injury, including paring, fracture, and bulb injury., Methods: Seven healthy patients who underwent hair transplant surgery by FUE were enrolled in the study. For each patient, 10 single-hair follicular unit grafts per injury group (paring, fracture, bulb injury, or intact) were differentiated. Using sharp implanters, 10 grafts of each of the 4 injury types were transplanted into mice, and the mice were sacrificed 5 months after transplantation. The skin was excised at each of the 4 locations, and newly formed follicular units were counted and photographed under a microscope., Results: Of 70 hair follicles in each group, the number of successfully engrafted follicles was 50 (71.43%) in the intact group, 36 (51.43%) in the paring injury group, 9 (12.86%) in the fracture injury group, and 31 (44.29%) in the bulb injury group., Conclusion: Grafts with minor injury had a lower survival rate than intact grafts. Fractured follicles showed the lowest survival rate., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aim: The aim of this study was to estimate the value of identifying vesicoureteral reflux (VUR) on a voiding cystourethrogram (VCUG) and the benefit of VUR management according to imaging strategies at the first febrile urinary tract infection (UTI)., Methods: Children aged 1-144 months (n = 618) with the first febrile UTI admitted at our hospital from 2000 to 2009 were enrolled. In all patients, renal sonogram (US), (99m) Tc-dimercaptosuccinic acid (DMSA) renal scanning and VCUG were performed. Retrospective analyses per patient and per renal unit were performed., Results: Abnormal US or DMSA scans had a sensitivity of 100% and a negative predictive value (NPV) of 100% to detect high-grade reflux. In hydronephrotic kidneys, DMSA scanning had a sensitivity of 88.2% and a NPV of 97.1% to detect high-grade reflux., Conclusion: Routine VCUG is not required after the first febrile UTI in patients with normal US or normal DMSA scan. Even if the US reveals hydronephrosis, routine VCUG is not necessary if the DMSA findings are normal. It is recommended that children who did not receive both a DMSA scan and VCUG after the first febrile UTI should be followed up over the long term., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

In a previous study, we recently claimed that dihydrotestosterone (DHT)-inducible dickkopf-1 (DKK-1) expression is one of the key factors involved in androgen-potentiated balding. We also demonstrated that L-ascorbic acid 2-phosphate (Asc 2-P) represses DHT-induced DKK-1 expression in cultured dermal papilla cells (DPCs). Here, we investigated whether or not L-threonate could attenuate DHT-induced DKK-1 expression. We observed via RT-PCR analysis and enzyme-linked immunosorbent assay that DHT-induced DKK-1 expression was attenuated in the presence of L-threonate. We also found that DHT-induced activation of DKK-1 promoter activity was significantly repressed by L-threonate. Moreover, a co-culture system featuring outer root sheath (ORS) keratinocytes and DPCs showed that DHT inhibited the growth of ORS cells, which was then significantly reversed by L-threonate. Collectively, these results indicate that L-threonate inhibited DKK-1 expression in DPCs and therefore is a good treatment for the prevention of androgen-driven balding.

Mast cell-mediated allergic symptoms are involved in many diseases, such as asthma and sinusitis. In this study, we investigated the effect of ethanol extract of fruits of Prunus persica (L) Batsch (FPP) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. FPP dose-dependently inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated local allergic reactions. Histamine releasing from mast cells was reduced by FPP, which was mediated by modulation of intracellular calcium. In addition, FPP attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-stimulated expression and secretion of pro-inflammatory cytokines in human mast cells. The inhibitory effect of FPP on pro-inflammatory cytokines was nuclear factor (NF)-kappaB dependent. Our findings provide evidence that FPP inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Acne is a complex, chronic and common skin disorder of pilosebaceous units. Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes via androgen stimulation and inflammatory cytokines are the major factors involved in the pathophysiology of acne. In addition, it is known that keratinocytes play an important role in acne synthesizing a number of inflammatory cytokines. However, the nature of the association between inflammatory cytokines and sebocytes in acne remains unclear. Culture of sebocytes provides a new insight into the participation of dihydrotestosterone (DHT) in the production of inflammatory cytokines in acne. To examine the possible involvement of DHT in the production of inflammatory cytokines in the cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha). Upregulation of IL-6 and TNF-alpha in immunohistochemistry, and increase in RNA amplification for IL-6 and TNF-alpha were observed after addition of DHT compared with the control. This study suggests that DHT may not only be involved in sebum production but also in production of proinflammatory cytokines in acne.

This paper reports a morphometric study of the C2 laminae to provide quantitative anatomical data for safe crossing laminar screw placement. A valid trajectory is essential for C2 crossing laminar screw placement. Although several clinical technique notes and modifications to define a safe screw trajectory have been introduced in the recent years, no morphometric analysis has been performed to confirm the accuracy of screw trajectory using this technique. In this study, morphometric analysis was performed on 100 Korean C2 three-dimensional reconstruction CT images. The reconstructive C2 vertebrae from the post-edge of the spinal canal to the spinal process were divided into several zones, 1 mm each. Each zone was chosen as the entry point to imitate a crossing laminar screw (3.5 mm diameter) placement. In each 1-mm zoned trajectory, the screw pass ratio (PR), safe screw angle range (SAR) and maximum screw length (MSL) were measured and compared with the data from the other zoned trajectories. The zone '5-6 mm posterior to the post-edge of the spinal canal' was found to be a more feasible and safer entry point for guiding a crossing laminar screw placement than the other zones because this zone could provide a trajectory with maximal PR (85%), SAR (9.57 +/- 4.36 masculine) and a larger MSL (21.74 +/- 2.44 mm) than the other areas. The recommended safe screw angle in the axial plane is 49.68 +/- 4.94 to 59.19 +/- 4.70 masculine. However, the screw angle can vary considerably according to the individual variance. A preoperative evaluation of the screw trajectory is essential for safe screw placement using this technique.

Objective: Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with Bispectral index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring., Methods: We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing., Results: The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were 0.63 +/- 0.26 in low dose group, and 1.31 +/- 0.48 in high dose group. The treatment durations were 4.89 +/- 1.68 days and 3.38 +/- 1.24 days in low dose BCT and high dose BCT, respectively., Conclusion: It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.

Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326-1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study.

Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the virtual absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is transmitted by an X-linked recessive gene or rarely an autosomal recessive gene. Therefore it is only males who fully express the condition. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Typically there is frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmentation, and absence of teeth. Those affected show great intolerance to heat. In the current absence of effective treatment for many hereditary skin diseases, comprehensive, accurate prenatal or postnatal genetic counseling can provide information to parents at risk of having affected children. We report HED in a 6-year-old boy with an Ala349Thr (GCA --> ACA) missense mutation developed de novo. Both parents and a 16-week gestational age fetus were healthy. We thought direct sequencing analysis for the ED1 gene using peripheral blood or amniotic fluid was preferable for an accurate diagnosis of this disease, although there was some risk of not detecting the mutation. After the results of this study were communicated to the parents, the mother was freed of her guilty feelings of the past 6 years and has now delivered a healthy male infant.

Overexpression of cyclooxygenase 2 (COX-2) is associated with the development of a number of human cancers including hepatocellular carcinoma (HCC). In addition, NS398, a selective COX-2 inhibitor, has been found to inhibit the growth of COX-2 expressing HCC cell lines. However, the mechanism of this effect remains unclear. Here, we report that NS398 inhibits the growth of the Hep 3B human HCC cell line and that inhibition results from the induction of apoptosis with no evidence of cell cycle arrest. We also show that the extent of apoptosis is greatly influenced by culture conditions. The NS398-induced apoptosis in Hep 3B cells is caspase-independent. Our data point to the feasibility of preventing HCC by means of COX-2 inhibitors, and show that the environment influences the cytotoxic effect of NS398 on cancer cells.

Overexpression of cyclooxygenase 2 (COX-2) is associated with tumorigenesis in a number of human cancers. Recently, COX-2 overexpression has also been reported in hepatocellular carcinoma (HCC), especially in well-differentiated HCC. However, doubt has been cast on these claims concerning HCC. Here we show by Western blot analysis that COX-2 protein level is higher in the adjacent chronic hepatitis liver than in the tumors themselves. We also show, by immunohistochemical staining, that the mean intensity of COX-2 expression in cirrhotic liver specimens is significantly higher than in normal livers and in moderately-differentiated HCC. In addition, the frequency and level of expression of COX-2 in poorly differentiated HCC was similar to that of well-differentiated HCC. Nevertheless all types of HCC expressed more COX-2 than normal livers, and immunofluorescence staining showed cytoplasmic expression of COX-2 in 7 out of 8 human hepatoma cell lines. Collectively, our data suggest that both chemoprevention and chemotherapy of HCC by COX-2 specific inhibitors should be considered. Our data also suggest that COX-2 may play a role in the advanced stages as well as early stages of hepatocarcinogenesis.

We have examined the frequency of SNP polymorphisms within the melanocortin-1 receptor (MC1R) and agouti signaling protein (ASIP) genes in 114 Korean vitiligo patients and 111 normal controls to assess the association of these loci with vitiligo risk. Using direct sequencing techniques, we found the following five MC1R coding region SNPs: Arg67Gln (G200A), Val92Met (G274A), Ile120Thr (T359C), Arg160Arg (C478A), and Gln163Arg (A488G). Of these, the most common were Val92Met at 14% in patients vs. 9% in controls (P = 0.17) and Gln163Arg at 17% in patients vs. 17% in controls (P = 0.84). Presence of the A allele of Val92Met (G274A) was higher in vitiligo patients [P = 0.12, odds ratio (OR) [95% confidence interval (CI)] = 1.68 (0.86-3.25)]. The other three variants showed a frequency <5% of both patients and controls. The ASIP 3'UTR genotype (g.8818A-G) was also assessed in the same subjects. The frequency of the G allele of 3'UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87-2.54)]. Carriage of the G allele was higher in vitiligo patients [P = 0.17, OR (95% CI) = 1.50 (0.83-2.72)], and those who also carried MC1R Val92Met were more prone to vitiligo [eight of 111 patients vs. four of 111 in controls, P = 0.14, OR (95% CI) = 2.75 (0.71-8.69)]. None of these associations, however, reached statistical significance.

We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.