Summary
Background
The normal stratum corneum (SC) has an upper basket‐weave (BW) pattern layer and a lower compact layer. The transition from compact to BW SC is well associated with a transition ...from diffuse to peripheral distributions of corneodesmosomes (CDs). The loss of transition from compact SC to BW SC appears to cause structural and barrier‐function impairments.
Objectives
To show the involvement of the BW SC in maintaining the physiological properties of the skin.
Methods
Reconstructed human epidermis (RHE) with a complete BW structure was created by treatment with prepared emulsion‐A, an oil‐in‐water emulsion. The RHE tissues were subjected to histological analysis, and the distribution of CDs on the SC with or without BW SC was analysed by anti‐desmoglein (Dsg)1 antibody immunofluorescence and ultrastructural and Western blotting analyses. Ultrastructural analysis of intercellular lipids was performed. The mechanical properties of the RHE were evaluated.
Results
Emulsion‐A successfully generated the BW SC in the RHE in which the degradation of CDs was promoted. The intercellular space of the BW SC generated by emulsion‐A was filled with multilamellar lipid sheets. The softness of the SC with a BW structure formed with emulsion‐A was higher than that of the compact SC in RHE. The outermost SC Dsg1 degradation (formation of the BW SC as determined with Dsg1 pixels) was correlated with water‐barrier functions and the SC softness of healthy human cheek, which varied widely.
Conclusions
Emulsion‐A successfully generated the BW SC in RHE for the first time. This method is suggested to be a useful tool for investigating the physiological significance of the BW SC in vitro. Determination of Dsg1 content in the SC obtained by tape stripping from human skin allows study of the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy.
What's already known about this topic?
The normal stratum corneum (SC) has two layers, an upper basket‐weave (BW) pattern layer and a lower compact layer.
Epidermal diseases such as ichthyosis vulgaris and X‐linked ichthyosis have an incomplete or no BW SC and impaired SC barrier functions, in which corneodesmosome (CD) degradation in a peripheral distribution is impaired.
The roles of the BW SC in the physiological properties of human skin have not been clearly elucidated.
What does this study add?
Reconstructed human epidermis (RHE) with a complete BW structure was generated for the first time by treatment with oil‐in‐water emulsion‐A.
The formation of the BW SC was associated with a decrease in Dsg1 content, which represents the CD number in the SC.
The intercellular space of the BW SC generated by emulsion‐A, but not compact SC, was filled with multilamellar lipid sheets.
The softness of the SC with a BW structure formed by emulsion‐A treatment was higher than that of the compact SC in RHE.
What is the translational message?
RHE with a complete BW SC generated by emulsion‐A treatment is suggested to be a useful tool for investigating effects on the physiological functions of the BW SC, as in treatments with creams and ointments including cosmetics.
Determination of desmoglein 1 content in the SC obtained by tape stripping from human skin can make it possible to study the effects of external stimulants, such as creams and ointments, including cosmetics, on the completeness of the BW SC in situ without biopsy.
Linked Comment: Ishida‐Yamamoto. Br J Dermatol 2020; 182:269–270.
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Accurate discrimination of orbital lymphoma from benign orbital lymphoproliferative disorders is crucial for treatment planning. We evaluated MR imaging including DWI and contrast-enhanced MR imaging ...for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders.
Forty-seven histopathologically proved orbital lymphoproliferative disorders (29 orbital lymphomas and 18 benign orbital lymphoproliferative disorders) were evaluated. Two board-certified radiologists reviewed visual features on T1-weighted, fat-suppressed T2-weighted, diffusion-weighted, and contrast-enhanced MR images. For quantitative evaluation, ADC and contrast-enhancement ratio of all lesions were measured and optimal cutoff thresholds and areas under curves for differentiating orbital lymphoma from benign orbital lymphoproliferative disorders were determined using receiver operative characteristic analysis; corresponding sensitivities and specificities were calculated.
Multivariate logistic regression analysis showed that ill-defined tumor margin (P = .003) had a significant association with orbital lymphoma whereas the "flow void sign" (P = .005) and radiologic evidence of sinusitis (P = .0002) were associated with benign orbital lymphoproliferative disorders. The mean ADC and contrast-enhancement ratio of orbital lymphomas were significantly lower than those of benign orbital lymphoproliferative disorders (P < .01). An ADC of less than 0.612 × 10(-3) mm(2)/s and a contrast-enhancement ratio of less than 1.88 yielded areas under curves of 0.980 and 0.770, sensitivity of 94.1% and 95.5%, and specificities of 93.3% and 80.0% for predicting orbital lymphoma, respectively.
Some characteristic MR imaging features and quantitative DWI and contrast-enhanced MR imaging are useful in further improving the accuracy of MR imaging for differentiation of orbital lymphoma from benign orbital lymphoproliferative disorders.
一项使用两种方法检查称为网状编织图案上层皮肤层的研究 Goto, H.; Tada, A.; Ibe, A. ...
British journal of dermatology (1951),
February 2020, 20200201, Volume:
182, Issue:
2
Journal Article
Summary
The skin is made up of several layers, the very outermost of which is the stratum corneum. The normal stratum corneum (SC) itself has two layers, an upper basket‐weave (B‐W) pattern layer ...and, below this, a lower compact layer. Corneodesmosomes are cells found in the stratum corneum, and in healthy skin, their number decreases (the cells degrade) from the lower compact layer up to the upper basket‐weave pattern layer, and their distribution (layout) changes. This can be seen by a process that looks at levels of desmoglein 1 (Dsg1) in skin cell samples taken on sticky tape (tape stripping), as levels of Dsg1 represent the numbers of corneodesmosomes. In some skin diseases such as ichthyosis vulgaris and X‐linked ichthyosis, there is no basket‐weave pattern layer, or it is incomplete.
In this study, the function of the upper basket‐weave pattern layer was explored, using reconstructed human epidermis (RHE, a type of model of skin developed from skin cells) as well as skin cells taken from female volunteers by tape stripping.
The scientists used an oil‐in‐water emulsion, prepared cream‐A, and successfully generated the upper basket‐weave pattern layer in reconstructed human epidermis in which the degradation of corneodesmosomes was promoted. This could be a useful tool for investigating the physiological significance of the basket weave layer in vitro (meaning in the lab rather than on humans).
Using the cells from the female volunteers, the researchers found that degradation of Dsg1 in the outermost stratum corneum, which represents the basket‐weave pattern layer forming, was correlated with water‐barrier functions (a sign of a healthy skin barrier) and the SC softness of healthy skin, which varied widely. Being able to measure Dsg1 content in the stratum corneum obtained by tape‐stripping from human skin, can make it possible to study the effects of external stimulants, such as creams/ointments, on the completeness of the basket weave layer without the need for a biopsy.
This summary relates to the study: Basket‐weave structure in the stratum corneum is an important factor for maintaining the physiological properties of human skin as studied using reconstructed human epidermis and tape stripping of human cheek skin
Linked Article: Goto et al. Br J Dermatol 2020; 182:364–372
In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which ...maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.
Checkpoint signaling requires two conserved phosphatidylinositol 3-kinase-related protein kinases (PIKKs): ATM and ATR. In budding yeast, Tel1 and Mec1 correspond to ATM and ATR, respectively. The ...Tel2-Tti1-Tti2 (TTT) complex connects to the Rvb1-Rvb2-Tah1-Pih1 (R2TP) complex for the protein stability of PIKKs; however, TTT-R2TP interaction only partially mediates ATM and ATR protein stabilization. How TTT controls protein stability of ATM and ATR remains to be precisely determined. Here we show that Asa1, like Tel2, plays a major role in stabilization of newly synthesized Mec1 and Tel1 proteins whereas Pih1 contributes to Mec1 and Tel1 stability at high temperatures. Although Asa1 and Pih1 both interact with Tel2, no Asa1-Pih1 interaction is detected. Pih1 is distributed in both the cytoplasm and nucleus wheres Asa1 localizes largely in the cytoplasm. Asa1 and Pih1 are required for proper DNA damage checkpoint signaling. Our findings provide a model in which two different Tel2 pathways promote protein stabilization of Mec1 and Tel1 in budding yeast.
Summary
Background
The aetiology for nonsteroidal anti‐inflammatory drug (NSAID)‐induced small intestinal injuries has not been well characterised.
Aim
To determine the risk factors of symptomatic ...NSAID‐induced small intestinal injuries, including diaphragm disease.
Methods
Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double‐balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5’‐nuclease assays.
Results
Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID‐induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID‐induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05–8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04–24.40, P = 0.002, respectively). The combination of aspirin and non‐aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34–1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55–108.36, P = 0.018, respectively).
Conclusion
The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.
Tetherin (BST-2/CD317/HM1.24) is an antiviral membrane protein that prevents the release of enveloped viruses from the cell surface. We found that the growth of human parainfluenza virus type 2 ...(hPIV-2), but not that of V protein-deficient recombinant hPIV-2, was inhibited by tetherin. V protein immunoprecipitates with tetherin, and this interaction requires its C-terminal Trp residues. The glycosyl phosphatidylinositol attachment signal of tetherin, but not its cytoplasmic tail, was necessary for its binding with V. The distribution of the V protein clearly changed when co-expressed with tetherin in plasmid-transfected cells. hPIV-2 infection of HeLa cells reduced cell surface tetherin without affecting total cellular tetherin. This reduction also occurred in HeLa cells constitutively expressing V, whereas mutated V protein did not affect the cell surface tetherin. Our results suggest that hPIV-2 V protein antagonizes tetherin by binding it and reducing its presence at the cell surface.
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