TSLP Induces Mast Cell Development and Aggravates Allergic Reactions through the Activation of MDM2 and STAT6

Thymic stromal lymphopoietin (TSLP) is known to promote T helper type 2 cell–associated inflammation. Mast cells are major effector cells in allergic inflammatory responses. We noted that the population and maturation of mast cells were reduced in TSLP-deficient mice (TSLP-/-). Thus, we hypothesized that TSLP might affect mast cell development. We found that TSLP induced the proliferation and differentiation of mast cells from bone marrow progenitors. TSLP-induced mast cell proliferation was abolished by depletion of mouse double minute 2 (MDM2) and signal transducers and activators of transcription 6 (STAT6), as an upstream activator of MDM2. TSLP-/-, in particular, had a considerable deficit in the expression of MDM2 and STAT6. Also, the TSLP deficiency attenuated mast cell–mediated allergic reactions through the downregulation of STAT6 and MDM2. In an antibody microarray chip analysis, MDM2 expression was increased in atopic dermatitis patients. These observations indicate that TSLP is a factor for mast cell development, and that it aggravates mast cell–mediated immune responses

Osteitis Fibrosa Cystica Mistaken for Malignant Disease

A 65-year-old man with back pain had plain radiographs that showed multiple osteolytic bone lesions of the pelvis, femur and L-spine; an magnetic resonance imaging scan of the L-spine showed extensive bony resorption with a posterior epidural mass involving the L1 spinous process; these findings suggested multiple myeloma or bony metastasis. However, all serology testing was negative. The parathyroid hormone and serum calcium levels were found to be abnormally elevated. A fine needle aspiration biopsy suggested that the L-spine lesion was consistent with the diagnosis of osteitis fibrosa cystica. A pathological fracture of the spine compressed the spinal cord, and surgical intervention was required. The neck computed tomography and Tc-99m sestamibi scan showed a solitary parathyroid mass. A minimally invasive parathyroidectomy using intraoperative parathyroid hormone monitoring was performed and two enlarged parathyroid glands identified. This case illustrates the importance of the consideration of a rare brown tumor associated with primary hyperparathyroidism in patients with the bone lesions suggestive of a malignancy

Association between periodontitis and hemorrhagic stroke among Koreans: A case-control study

Background: Several studies suggested that periodontitis is a risk factor for stroke, but the relationship between periodontitis and hemorrhagic stroke has not been widely reported. This study aims to evaluate the association between periodontitis and hemorrhagic stroke and to identify the risk group for this association. Methods: We recruited 165 patients who were diagnosed via computed tomography brain imaging as having had a hemorrhagic stroke and 214 non-stroke control subjects for a case-control study. All participants underwent a clinical periodontal examination using clinical attachment level (CAL) as amarker. Information about sociodemographic factors, behavioral factors, systemic health, and a familial history of systemic health was gathered through an interview using structured questionnaires. The association between periodontitis and hemorrhagic stroke was evaluated using multivariate logistic regression analyses with adjustment for age, gender, income, education, hypertension, diabetes, body mass index, cardiac disease, familial hypertension history, familial diabetes history, familial cardiac disease history, smoking, and alcohol consumption. Subgroup analyses were also performed to investigate potential risk groups. Results: After controlling for potential confounders, periodontitis (CAL ≥6 mm) was found to be significantly associated with hemorrhagic stroke (odds ratio: 2.5; 95% confidence interval: 1.1 to 5.6), but this association did not exhibit a dose-dependent response for periodontitis (percentile of sites of periodontal pockets with CAL ≥5 mm among total probed pockets). The association between periodontitis (CAL ≥6 mm) and hemorrhagic stroke was significant for males, patients who had a lower income than control subjects, obese patients, and patients without diabetes. Conclusions: Periodontitis may be an independent risk factor for hemorrhagic stroke. Risk groups include males, patients without diabetes, and obese subjects

Long-term clinical course of a patient with mucopolysaccharidosis type IIIB

Mucopolysaccharidosis type III (MPS III) is a rare genetic disorder caused by lysosomal storage of heparan sulfate. MPS IIIB results from a deficiency in the enzyme alpha-N-acetyl-D-glucosaminidase (NAGLU). Affected patients begin showing behavioral changes, progressive profound mental retardation, and severe disability from the age of 2 to 6 years. We report a patient with MPS IIIB with a long-term follow-up duration. He showed normal development until 3 years. Subsequently, he presented behavioral changes, sleep disturbance, and progressive motor dysfunction. He had been hospitalized owing to recurrent pneumonia and epilepsy with severe cognitive dysfunction. The patient had compound heterozygous c.1444C>T (p.R482W) and c.1675G>T (p.D559Y) variants of NAGLU. Considering that individuals with MPS IIIB have less prominent facial features and skeletal changes, evaluation of long-term clinical course is important for diagnosis. Although no effective therapies for MPS IIIB have been developed yet, early and accurate diagnosis can provide important information for family planning in families at risk of the disorder

Genomic characterization of Nocardia seriolae strains isolated from diseased fish

Members of the genus Nocardia are widespread in diverse environments; a wide range of Nocardia species are known to cause nocardiosis in several animals, including cat, dog, fish, and humans. Of the pathogenic Nocardia species, N. seriolae is known to cause disease in cultured fish, resulting in major economic loss. We isolated two N. seriolae strains, CK‐14008 and EM15050, from diseased fish and sequenced their genomes using the PacBio sequencing platform. To identify their genomic features, we compared their genomes with those of other Nocardia species. Phylogenetic analysis showed that N. seriolae shares a common ancestor with a putative human pathogenic Nocardia species. Moreover, N. seriolae strains were phylogenetically divided into four clusters according to host fish families. Through genome comparison, we observed that the putative pathogenic Nocardia strains had additional genes for iron acquisition. Dozens of antibiotic resistance genes were detected in the genomes of N. seriolae strains; most of the antibiotics were involved in the inhibition of the biosynthesis of proteins or cell walls. Our results demonstrated the virulence features and antibiotic resistance of fish pathogenic N. seriolae strains at the genomic level. These results may be useful to develop strategies for the prevention of fish nocardiosis.

Comparison of 1.5T and 3T 1H MR Spectroscopy for Human Brain Tumors

OBJECTIVE: We wanted to estimate the practical improvements of 3T proton MR spectroscopy ((1)H MRS) as compared with 1.5T (1)H MRS for the evaluation of human brain tumors. MATERIALS AND METHODS: Single voxel (1)H MRS was performed at both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data acquisition parameters at both field strengths, the (1)H MRS spectra were obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec) with the voxel size ranging from 2.0 cm(3) to 8.7 cm(3). The signal to noise ratios (SNRs) of the metabolites (myoinositol [MI], choline compounds [Cho], creatine /phosphocreatine [Cr], N-acetyl-aspartate [NAA], lipid and lactate [LL]) and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at both TEs between the two field strengths in each brain tumor. The degrees of spectral resolution between the Cho and Cr peaks were qualitatively compared between the two field strengths in each brain tumor. RESULTS: The SNRs of the metabolites at 3T demonstrated 49-73% increase at a short TE (p 0.05) compared with those of 1.5T. The SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer inversion at 3T (p < 0.05). There was no significant difference in the metabolite ratios between the two field strengths. The degrees of the spectral resolution at 3T were slightly superior to those of 1.5T at a short TE. CONCLUSION: As compared with 1.5T, 3T 1H MRS demonstrated 49-73% SNR increase in the cerebral metabolites and slightly superior spectral resolution only at a short TE, but little at an intermediate TE, in the brain tumors. There was no significant difference in the metabolite ratios between the two field strengths