Accurate quantification of high-purity uranium in coatings by small solid angle method.

Aiming at quantifying high-purity uranium (235U/236U/238U) in coatings, a series of experiments were carried out by a dedicated small solid angle device. The physical design of the device and the small solid angle method were here in described, focus in particular on the analysis of detection efficiency, the effect of the isotope impurity in the coatings and the correction for the non-uniform distribution of the uranium samples. The results show that the weight of 235U in the coatings is 5.2-5.6 mg, while 4.7-5.0 mg for 238U and 2.2 mg for 236U in the corresponding coatings, with relative experimental uncertainties of 1.0%--1.2%.

Classification of non-tumorous skin pigmentation disorders using voting based probabilistic linear discriminant analysis.

Non-tumorous skin pigmentation disorders can have a huge negative emotional impact on patients. The correct diagnosis of these disorders is essential for proper treatments to be instituted. In this paper, we present a computerized method for classifying five non-tumorous skin pigmentation disorders (i.e., freckles, lentigines, Hori's nevus, melasma and nevus of Ota) based on probabilistic linear discriminant analysis (PLDA). To address the large within-class variance problem with pigmentation images, a voting based PLDA (V-PLDA) approach is proposed. The proposed V-PLDA method is tested on a dataset that contains 150 real-world images taken from patients. It is shown that the proposed V-PLDA method obtains significantly higher classification accuracy (4% or more with p< 0.001 in the analysis of variance (ANOVA) test) than the original PLDA method, as well as several state-of-the-art image classification methods. To the authors' best knowledge, this is the first study that focuses on the non-tumorous skin pigmentation image classification problem. Therefore, this paper could provide a benchmark for subsequent research on this topic. Additionally, the proposed V-PLDA method demonstrates promising performance in clinical applications related to skin pigmentation disorders.

Indeterminate cell histiocytosis in a Chinese patient with progressive and extensive nodular lesions and mixed indeterminate cell and macrophage-monocyte lineage.

Indeterminate cell histiocytosis (ICH) is an extremely rare cutaneous neoplastic disorder. It has the immunophenotypic features of both Langerhans and non-Langerhans cell histiocytosis. We report here a case of a healthy young Chinese woman who presented with disfiguring, thick, infiltrated cutaneous nodules on the face, trunk and extremities which appeared progressively over a period of 4 years. No systemic involvement has been detected so far. Results of a skin biopsy showed diffuse dermal infiltration of histiocytoid cells with indented nuclei and positive staining for S100 and CD1a and negativity for CD207 (langerin). Admixed within were some CD68-positive foamy histiocytes and multinucleated giant cells with focal expression of CD163. Although the clinical presentation is more typical of progressive nodular histiocytosis, the histology and immunoprofile is consistent with ICH. Our report adds to the limited case reports in the current literature of ICH in the Chinese population.

A case series of imatinib-induced generalized hypopigmentation and progression of existing acquired dermal melanocytosis.

Imatinib mesylate is a tyrosine kinase inhibitor used in the treatment of oncological conditions, including chronic myeloid leukemia and gastrointestinal stromal tumors. The most frequent dermatological side effect reported is pigmentary abnormalities. We report a case series of three Asian Chinese females with preexisting acquired dermal melanocytosis that progressed after initiation of imatinib treatment, and concurrently developed generalized hypopigmentation of the skin. All three patients had similar histological findings on skin biopsy. It is postulated that the KIT/SCF pathway has a central role in the pathogenetic mechanism. Therefore, it is important for physicians to be aware of this potential side effect of paradoxical pigmentation in patients treated with imatinib.

Actinic Prurigo in Singaporean Chinese: A Positive Association with HLA-DRB1*03:01.

Studies have reported the association of human leukocyte antigen (HLA) genes with susceptibility to develop actinic prurigo (AP) in Caucasians, but there were no studies in Asian populations, including the Chinese. Our study was performed to determine if AP is associated with susceptibility or protective HLA alleles or haplotypes in Singaporean Chinese. All Chinese patients diagnosed with AP at National Skin Center, Singapore, from January 2002 to April 2015 were invited to participate in the study. Clinical data and phototesting results were collated, and HLA typing was performed. Among 14 patients included, 11 were male and the mean age was 49.6 (37.9-61.3) years. All patients did not have a family history of AP and none had mucosal involvement, as such these clinical features differed from Caucasian AP patients. The frequency of DRB1*03:01 in AP patients was significantly higher compared to healthy controls (43% vs 16%, P = 0.022, odds ratio (OR) 3.89). Concurrently, the frequency of HLA-B*58:01-DRB1*03:01 haplotype was also significantly increased (25% vs 7%, P = 0.004, OR 4.23). In conclusion, HLA-DRB1*03:01 was associated with AP in Singaporean Chinese patients. This novel allelic association may possibly be utilized as a biological marker to aid in the diagnosis of AP in Chinese patients.

Epidermolysis bullosa pruriginosa: a case with a novel mutation and co-existent lichen amyloidosus.

Epidermolysis bullosa pruriginosa is a rare variant of dystrophic epidermolysis bullosa characterized by severely pruritic and cicatricial lesions localized to the extensor extremities. We report a Singaporean Chinese male with epidermolysis bullosa pruriginosa with an underlying novel mutation in the COL7A1 gene. A heterozygous acceptor splice site mutation IVS67-1G>T probably led to in-frame skipping of exon 68 (36-basepairs), resulting in a loss of 12 amino acids. Among his three children, only the youngest son, who had bilateral big toenail thickening, possessed the same mutation. His skin biopsy one decade ago revealed association of focal amyloidosis; a recent skin biopsy showed more established features of lichen amyloidosis. It is debatable whether the cutaneous amyloidosis was a secondary or primary phenomenon. Our report highlights that the diagnosis of epidermolysis bullosa pruriginosa may be obscured when cutaneous amyloidosis is coexistent.

Lipoid proteinosis in a Chinese patient.

Lipoid proteinosis is a rare autosomal recessive deposition disorder due to loss-of-function mutations in the gene encoding extracellular matrix protein 1 on chromosome 1q21. There are limited case reports of lipoid proteinosis in the Chinese population. The authors report 1 case of lipoid proteinosis in a Chinese patient with typical clinical and histopathological manifestations. Physical examination in this patient demonstrated hoarse voice, hypertrophy of tongue and lips, inability to fully protrude the tongue, and cutaneous features including moniliform blepharosis, verrucous plaques, and scarring. Biopsies from the eyelid, pharyngeal mucosa, and elbow lesions revealed diffuse amorphous deposits of hyaline material within the dermis and around blood vessels, which stained positively for periodic acid-Schiff, was diastase resistant and stained negatively on Congo red.

Directed differentiation of human embryonic stem cells into the pancreatic endocrine lineage.

Human embryonic stem (hES) cells represent a potentially unlimited source of transplantable beta-cells for the treatment of diabetes. Here we describe a differentiation strategy that reproducibly directs HES3, an National Institutes of Health (NIH)-registered hES cell line, into cells of the pancreatic endocrine lineage. HES3 cells are removed from their feeder layer and cultured as embryoid bodies in a three-dimensional matrix in the presence of Activin A and Bmp4 to induce definitive endoderm. Next, growth factors known to promote the proliferation and differentiation of pancreatic ductal epithelial cells to glucose-sensing, insulin-secreting beta-cells are added. Pdx1 expression, which identifies pancreatic progenitors, is detected as early as day 12 of differentiation. By day 34, Pdx1+ cells comprise between 5% and 20% of the total cell population and Insulin gene expression is up-regulated, with release of C-peptide into the culture medium. Unlike another recent report of the induction of insulin+ cells in differentiated hES cell populations, we are unable to detect the expression of other pancreatic hormones in insulin+ cells. When transplanted into severe combined immunodeficiency (SCID) mice, differentiated cell populations retain their endocrine identity and synthesize insulin.

Adenoviral gene transfer of PDGF downregulates gas gene product PDGFalphaR and prolongs ERK and Akt/PKB activation.

The delivery of platelet-derived growth factor (PDGF) for tissue engineering of skin and periodontal wounds has become an active area of interest. However, little is known regarding the extended effects of PDGF on cell signaling via gene therapy and how such an approach facilitates the exiting of cells from growth arrest and entry to competence required for cell cycling. We show in vitro expression and secretion of PDGF-AA by recombinant adenovirus encoding the PDGF-A gene (Ad-PDGF-A). The bioactive PDGF-AA protein released induces sustained downregulation of PDGFalphaR that is encoded by a growth arrest-specific (gas) gene. Ad-PDGF-A induces sustained phosphorylation of PDGFalphaR as well as prolonged phosphorylation of downstream extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Furthermore, the phosphorylation of PDGFalphaR is abolished by cotransducing cells with adenovirus encoding a dominant negative mutant of the PDGF-A gene that disrupts PDGF bioactivity. These findings demonstrate the prolonged effects of adenoviral delivery of PDGF and aid in the better understanding of sustained PDGF signaling.

Basal and stimulated protein S-nitrosylation in multiple cell types and tissues.

There is substantial evidence that protein S-nitrosylation provides a significant route through which nitric oxide (NO)-derived bioactivity is conveyed. However, most examples of S-nitrosylation have been characterized on the basis of analysis in vitro, and relatively little progress has been made in assessing the participant forms of nitric-oxide synthase (NOS) or the dynamics of protein S-nitrosylation in situ. Here we utilize antibodies specific for the nitrosothiol (SNO) moiety to provide an immunohistochemical demonstration that protein S-nitrosylation is coupled to the activity of each of the major forms of NOS. In cultured endothelial cells, SNO-protein immunoreactivity increases in response to Ca(2+)-stimulated endothelial NOS (eNOS) activity, and in aortic rings, endothelium-derived and eNOS-mediated relaxation (EDRF) is coupled to increased protein S-nitrosylation in both endothelial and associated smooth muscle cells. In cultured macrophages, SNO-protein levels increase upon cytokine induction of induced NOS (iNOS), and in PC12 cells, increased protein S-nitrosylation is linked to nerve growth factor induction of neuronal NOS (nNOS). In addition, we describe developmental and pathophysiological increases in SNO-protein immunoreactivity within human lung. These results, which demonstrate Ca(2+), neurohumoral, growth factor, cytokine, and developmental regulation of protein S-nitrosylation that is coupled to NOS expression and activity, provide unique evidence for the proposition that this ubiquitous NO-derived post-translational protein modification serves as a major effector of NO-related bioactivity.