Characterization of silver nanoparticle aggregates using single particle-inductively coupled plasma-mass spectrometry (spICP-MS).

The single particle-inductively coupled plasma-mass spectrometry was applied to characterize the aggregates of AgNPs. was applied to characterize the aggregates of AgNPs. Two sizes of citrate-AgNPs and PVP-AgNPs were used at relatively high and predicted environmental concentrations under various ionic strengths. Citrate-AgNP aggregated with increases in the ionic strength, whereas PVP-AgNPs were sterically stable. The critical coagulation concentrations were 85 mM and 100 mM NaNO3 for 60 nm and 100 nm citrate-AgNPs at 2 mg L-1 as total Ag obtained by dynamic light scattering (DLS). At 2 mg L-1 as total Ag, the mass of an aggregate gradually increased with increasing ionic strength for both citrate-AgNP during spICP-MS analyses. The average number of single particles derived from the mass in an aggregate was calculated to be 8.68 and 5.95 for 60 nm and 100 nm citrate-AgNPs at 85 mM and 100 mM NaNO3, respectively after 2 h. The mass fractal dimensions were determined to be 2.97 and 2.83, further implying that the aggregate structures were very rigid and compact. Only marginal increases in the average mass and number of single particles in the aggregate units were found during 24 h under environmentally relevant AgNP concentrations. The average number of single particles constituting an aggregate unit for 60 nm and 100 nm citrate-AgNPs was 1.24 and 1.37 after 24 h at a high ionic strength. These results indicate that under environmentally relevant conditions, the collision frequency is predominant in the aggregation and that NPs are likely to encounter natural colloids such as clay and organic matter to form hetero-aggregates.

MicroRNA-155 regulates the Th17 immune response by targeting Ets-1 in Behçet's disease.

OBJECTIVES: The goal of this study was to investigate whether microRNA-155 might be a potential therapeutic target for Behçet's disease (BD). METHODS: Expression levels of miR-155 were quantified using TaqMan microRNA assays in peripheral blood mononuclear cells and in isolated CD4+ T cells from BD patients and healthy controls. To identify targets of miR-155, luciferase reporter assays and western blotting were performed. The effect of miR-155 on Th17 polarisation was analysed in patients with active BD by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The expression of miR-155 and IL-17 was significantly increased in CD4+ T cells of patients with active BD. A luciferase reporter assay and western blot showed that Ets-1 expression was reduced by miR-155 mimics. Furthermore, the expression of Ets-1 was significantly decreased in patients with active BD compared to healthy controls. More importantly, repression of miR-155 in CD4+ T cells from active BD patients increased Ets-1 expression and reduced the number of IL- 17-expressing T cells and overall IL-17 production. CONCLUSIONS: MiR-155 regulates the Th17 immune response by targeting Ets-1. Suppression of miR-155 reduced the amount of pathogenic IL-17-expressing T cells and may be a potential therapeutic strategy for BD.

Genetic Polymorphisms in Autophagy-Associated Genes in Korean Children With Early-Onset Crohn Disease.

OBJECTIVE: The aim of the present study was to investigate the genetic polymorphisms of the autophagy-associated genes autophagy-related 16-like 1 (ATG16L1), immunity-related GTPase M (IRGM), Unc-51-like kinase 1 (ULK1), and NOD2 with respect to early-onset Crohn disease (CD) among Korean children. METHODS: A total of 65 patients with CD from the Seoul National University Children's Hospital, from January 2000 to May 2012, and 72 unaffected controls were selected. Twelve different single nucleotide polymorphisms (SNPs) were analyzed (TaqMan assay: ATG16L1 rs2241880, IRGM SNPs [rs13361189, rs4958847, rs1000113, rs10065172, and rs72553867], ULK1 SNPs [rs12303764, rs10902469, and rs7488085], NOD2 SNPs [Arg702Trp and Gly908Arg]; direct sequencing: NOD2 leu1007fsinsC). The onset age of patients was 8.6 ±â€Š4.7 years. Twelve patients (18.5%) had an onset age of <1 year. RESULTS: Two of the 12 SNPs showed significant results. IRGM rs1000113 exhibited an association with CD with respect to its minor allele frequency (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.05-2.79, P = 0.03) and genotype distribution (dominant model: OR 2.17, 95% CI 1.07-4.39, P = 0.03). IRGM rs72553867 exhibited association with CD with respect to its minor allele frequency (OR 0.50, 95% CI 0.27-0.91, P = 0.02) and genotype distribution (dominant model: OR 0.50, 95% CI 0.23-0.94, P = 0.03). The 3 SNPs of NOD2 existed only as wild types for both groups. In the genotype-phenotype analysis, the onset age, disease location, and disease behavior exhibited no association. CONCLUSIONS: IRGM rs1000113 and IRGM rs72553867 exhibited associations with early-onset CD as risk loci and defense loci, respectively. This suggests that the autophagy pathway plays an important role in early-onset CD.

Up-regulation of Th17 and related cytokines in Behçet's disease corresponding to disease activity.

OBJECTIVES: The IL-23/IL-17 pathway is implicated in the development of certain inflammatory diseases. The aim of the present study was to investigate the expression of Th17 and related cytokines according to clinical activity in Behçet's disease (BD). METHODS: Peripheral blood mononuclear cells (PBMCs) from eleven patients with active BD, eleven patients with inactive BD, ten patients with recurrent aphthous ulcers, and ten healthy controls were cultured and stained with the appropriate fluorescent antibodies for analysis by flow cytometry. ELISA assays were utilized to determine the concentrations of IL-17, IFN-γ, IL-23, and IL-12/23p40 in serum and culture supernatants. IL-12p35, IL-12/23p40, and IL-23p19 transcript levels in PBMCs were measured by real-time PCR. RESULTS: Significantly higher frequencies of IL-17 and IFN-γ expressing CD4(+) T cells were observed in patients with active BD compared with control groups. Similarly, levels of IL-17, IL-23, IL-12/23p40, and IFN-γ in serum and supernatants were significantly elevated in patients with BD despite the fact that IL-12p35 and IL-12/23p40 mRNA expression in PBMCs was up-regulated in the inactive BD group. In the same patient, the frequency of IL-17 expressing cells decreased when the BD disease activity was stabilised. CONCLUSIONS: The results of this study suggest that up-regulated IL-17 expression may be associated with clinical activity of BD.

Prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics.

The purpose of this study was to investigate the prevalence, clinical characteristics, and management of functional constipation at pediatric gastroenterology clinics. A prospective survey using the Rome III criteria was distributed to a group of parents of children with a constipation history and its control group in May 2008. The mean prevalence of constipation was 6.4%, which was similar to those in other countries. Statistically significant variables for children without constipation were that more children had a body mass index of below the 10th percentile even though they received more mother's care and ate balanced meals compared to the constipation group. Meanwhile, the constipation group frequently showed a history of constipation in infancy, picky-eating, lack of exercise, and retentive posturing. When analyzed with the Rome III criteria, the children showed greater than 60% rate of hard stools, painful stools, a history of large fecal mass in rectum, and its disappearance of constipation symptoms after passing a large stool. Our study found different approaches amongst pediatric gastroenterologists like rectal examinations, disimpaction, or drug treatment. Several factors addressed in our study can provide better guidelines for clinicians treating constipation and its future research.

Morbidity of solid cancer in Behςet's disease: analysis of 11 cases in a series of 506 patients.

PURPOSE: Behςet's disease (BD) is rarely reported to be associated with malignancies in the literature. However, the frequency of cancer in BD patients remains unknown. This study evaluated cancer morbidity in BD patients compared with that in the general population of Korea. MATERIALS AND METHODS: A retrospective chart review was performed on 506 patients visiting our hospital from 1994 to 2011 for BD. We analyzed the standardized morbidity rate (SMR), which is the ratio of observed to expected malignancies. Furthermore, we reviewed cases of solid cancer in BD patients in the literature. RESULTS: Of the 506 patients with BD, 11 (2.17%) developed cancer. We found a variety of solid cancers without predominance and no hematologic malignancies. The total number of cancers observed was less than expected, which was determined from the statistical data of the National Cancer Information Center of Korea, with an SMR of 0.023 (95% confidence interval, 0.012-0.039). CONCLUSION: BD may be associated with a lower cancer-related morbidity compared with the general population of Korea.

Analysis of Colonization and Genotyping of the Exotoxins of Staphylococcus aureus in Patients with Atopic Dermatitis.

BACKGROUND: The skin of atopic dermatitis (AD) patients has a high susceptibility to Staphylococcus aureus colonization, and the toxins produced by S. aureus may aggravate AD by acting as superantigens. OBJECTIVE: The purpose of this study was to evaluate the relationship of the skin barrier function, colonization of S. aureus, and the clinical severity of AD. We also examined the predominant toxin genes produced in Korean AD patients. METHODS: Thirty-nine patients with AD were evaluated for clinical severity and skin barrier function by using Severity Scoring of Atopic Dermatitis (SCORAD) index and transepidermal water loss (TEWL). S. aureus was isolated from the forearm, popliteal fossa, and anterior nares of AD patients (n=39) and age-matched controls (n=40); the toxin genes were analyzed by performing multiplex polymerase chain reaction. RESULTS: TEWL showed a statistically significant correlation with clinical severity in patients with AD (p<0.05). TEWL was correlated with the number of S. aureus colonization sites and the presence of nasal colonization, but these results were not statistically significant. S. aureus strains were isolated in 64.1% of the 39 AD patients. The SCORAD index and AD severity were strongly correlated with the number of colonization sites. The predominant toxin gene found in AD patients was staphylococcal enterotoxin a (sea) only, which was produced in 52.6% of patients. The toxin genes sea and toxic shock syndrome toxin-1 (tsst-1) were found together in 42.1%, while tsst-1 only was found in 5.3% of the patients. CONCLUSION: S. aureus strains were isolated in 64.1% of the 39 AD patients. Skin barrier function, as measured by TEWL, revealed a statistically significant correlation with clinical severity in AD patients. The SCORAD index and severity of AD was strongly correlated with the number of colonization. The most common toxin gene was sea in the Korean AD patients and this gene might have an important role in the pathogenesis of AD.

Eccrine angiomatous hamartoma mimicking a traumatic hemorrhage.

Eccrine angiomatous hamartoma (EAH) is a rare benign disease that is characterized by an abnormal proliferation of eccrine glands and vascular elements. It is generally congenital, but it can appear before puberty. It usually presents as a single plaque or nodule, but multiple patch-like lesions are also possible. EAH is mostly asymptomatic, but it is sometimes associated with pain or hyperhidrosis. It generally does not require aggressive treatment, but the lesion can be excised due to pain, enlargement and cosmetic reasons. A 3-week-old Korean female presented with a hemorrhagic skin lesion on the right foot since birth. There was no specific birth history. The lesion first appeared on the third toe of the right foot and quickly spread to almost half of the right foot. Histopathology examination revealed acanthosis in the epidermis and a proliferation of eccrine ducts, glands and capillaries. The eccrine glands were immunohistochemically-positive for carcinoembryonic antigen.

Basal cell carcinoma with myoepithelial differentiation: a distinct plasmacytoid cell variant with hyaline inclusions.

We describe a 74-year-old man presenting with a 10-year history of an asymptomatic, skin-colored hard plaque on his left cheek. Microscopy revealed well-demarcated tumor with peripheral palisading and peritumoral clefting in the dermis. The tumor included many plasmacytoid cells with cytoplasmic hyaline inclusions and eccentric nuclei. Electron microscopic examination showed that hyaline inclusions consisted of aggregates of filaments. Immunoperoxidase staining showed diffuse cytoplasmic expression of 34bE12, smooth muscle actin, calponin and p63. We diagnosed the patient with basal cell carcinoma (BCC) with myoepithelial differentiation and treated him with excision. Eight months postoperatively, the patient remained well with no recurrence. This distinct variant of BCC with myoepithelial differentiation, showing cytoplasmic hyaline inclusions and eccentric nuclei, has previously been confusingly termed 'signet-ring cell BCC'. However, these plasmacytoid cells differ from signet-ring cells with vacuolated cytoplasm. To avoid confusion, we suggest the designation 'BCC with myoepithelial differentiation'.

Chromoblastomycosis Caused by Phialophora richardsiae.

Chromoblastomycosis is a chronic fungal disease of the skin and subcutaneous tissues caused by a group of dematiaceous (black) fungi. The most common etiologic agents are Fonsecaea pedrosoi and Cladophialophora carrionii, both of which can be isolated from plant debris. The infection usually follows traumatic inoculation by a penetrating thorn or splinter wound. Several months after the injury, painless papules or nodules appear on the affected area; these papules then progress to scaly and verrucose plaques. We report a case of chromoblastomycosis caused by Phialophora richardsiae, which has been rarely associated with chromoblastomycosis. The case involved a 43-year-old male, who for the past 2 months had noted an erythematous, pustulous plaque that was somewhat dark brown in color on his right shin; the plaque also had intermittent purulent discharge and crust formation. On histopathological examination, chronic granulomatous inflammation and sclerotic cells were seen. The tissue fungus culture grew out the typical black fungi of P. richardsiae, which was confirmed by polymerase chain reaction. The patient has been treated with a combination of terbinafine and itraconazole for 3 months with a good clinical response.

A malignant melanoma associated with a blue nevus of the lip.

Blue nevi are characterized by a collection of pigment-producing melanocytes in the dermis. These lesions clinically present as well demarcated cerulean-blue or bluish black colored papules or plaques that usually measure less than 1 cm in diameter. They are typically found on the dorsal surface of the hands and feet or in the head and neck region; however, they are rarely found in the oral cavity. These lesions are usually benign and stable over time. However, malignant melanomas developing in or associated with a blue nevus (which is also called malignant blue nevus) have been only rarely reported. A malignant blue nevus might develop in a common blue or cellular blue nevus, a giant congenital nevus or in a nevus of Ota, or it may be malignant from the start. Malignant blue nevi most commonly are found on the scalp. A malignant blue nevus of the lip has not been previously reported in the medical literature. We report here on a patient with a malignant melanoma associated with a blue nevus of the lip. The malignant melanoma was presumed to have developed from a blue nevus that was present on the upper lip of a 50-year-old male.

A Case of Varicella Combined with Hand-foot-mouth Disease in a Healthy Child.

We report here on an 11-year-old child with a pustulovesicular eruption on her whole body, including her palms, soles and oral mucosa, and this was accompanied with fever. A serologic test was positive for IgM varicella zoster antibody and coxsackievirus A16 antibody. The histopathologic examination from the palm revealed intraepidermal pustules that showed neither inclusion bodies nor multinucleated giant cells. We made the final diagnosis, according to the serologic tests and histopathologic findings, as varicella combined with hand-foot-mouth disease caused by coxsackievirus A16 in a previously healthy child.

Ecthyma Gangrenosum: A Rare Cutaneous Manifestation Caused by Stenotrophomonas maltophilia in a Leukemic Patient.

Ecthyma gangrenosum (EG) is a well-recognized cutaneous infection that most commonly affects immunocompromised patients. It typically occurs on the extremities, or in gluteal and perineal regions. Although Pseudomonas aeruginosa is the most well-known pathogen causing EG, other organisms have been reported to cause EG. Herein we report a rare case of ecthyma gangrenosum presenting as aggressive necrotic skin lesions in perioral and infraorbital areas in a 47-year-old patient with acute myelocytic leukemia after allogeneic bone marrow transplantation. It was caused by Stenotrophomonas maltophilia, which is an aerobic, gram-negative pathogen that has been associated only rarely with cutaneous disease. Blood culture and tissue culture were positive for S. maltophilia. Histological examination revealed numerous tiny bacilli in the dermis and perivascular area. Early recognition of skin lesions caused by S. maltophilia is important to decrease associated mortality in immunosuppressed patients.

A Case of Cellulitis Associated with Coral Injury.

Corals are the marine organism that belongs to the phylum Cnidaria, and are one of the common causes of superficial injury in the marine environment. In addition to acute reactions such as burning or stinging pain and erythema, coral injuries may present with complications such as foreign body reactions, bacterial infections, and/or localized eczematous reactions. A 23-year-old male presented with an erythematous edematous tender patch with centrally grouped vesicles on the left ankle; the injury had occurred during skin-scuba diving 2 days before. A biopsy of the lesion treated with hematoxylin-eosin stain showed epidermal necrosis with subepidermal blisters and neutrophilic panniculitis. Herein we report a case of cellulitis caused by the nematocyst stings of corals.

FMRFamide-expressing efferent neurons in eighth abdominal ganglion innervate hindgut in the silkworm, Bombyx mori.

The tetrapeptide FMRFamide is known to affect both neural function and gut contraction in a wide variety of invertebrates and vertebrates, including insect species. This study aimed to find a pattern of innervation of specific FMRFamide-labeled neurons from the abdominal ganglia to the hindgut of the silkworm Bombyx mori using the immunocytochemical method. In the 1st to the 7th abdominal ganglia, labeled efferent neurons that would innervate the hindgut could not be found. However, in the 8th abdominal ganglion, three pairs of labeled specific efferent neurons projected axons into the central neuropil to eventually innervate the hindgut. Both axons of two pairs of labeled cell bodies in the lateral rind and axons of one pair of labeled cell bodies in the posterior rind extended to the central neuropil and formed contralateral tracts of a labeled neural tract with a semi-circular shape. These labeled axons ran out to one pair of bilateral cercal nerves that extended out from the posterior end of the 8th abdominal ganglion and finally to the innervated hindgut. These results provide valuable information for detecting the novel function of FMRFamide-related peptides in metamorphic insect species.