Estimated long-term dietary exposure to lead, cadmium, and mercury in young Korean children.

BACKGROUND: Controlling for day-to-day variation is a key issue in estimating long-term dietary exposure to heavy metals using 24-hour recall (24HR) data from a relatively small number of days. OBJECTIVES: This study was conducted to estimate long-term dietary exposure to lead, cadmium and mercury among Korean children using the Iowa State University (ISU) method and to assess the contributions of different food groups to heavy metal intake. METHODS: We analyzed 2 days of 24HR data from 457 children between 0 and 6 years of age in 2010. Using bootstrapped concentration data for 118 representative foods, 93.5% of total intake was included in the exposure estimates in this study. Using the 2-day exposure data, we estimated long-term exposure by controlling for within-individual variation using the ISU method. RESULTS: The long-term dietary exposure estimates (mean±standard deviation) for lead, cadmium, and mercury were 0.47±0.14, 0.38±0.20, and 0.22±0.08 µg/kg bw/day, respectively. For lead and cadmium, the percentages of children whose exposure was greater than the reference value were 35 and 42%, respectively. Fruits were an important source of lead exposure, and cereal and fish and shellfish made the greatest contributions to the total cadmium and mercury exposure. CONCLUSIONS: Our findings also suggest that the long-term exposure to lead and cadmium was somewhat greater than the reference values, whereas mercury exposure was well below than the reference value in this population. Further studies may be necessary to evaluate the food items contributing to heavy metal exposure, and continuous monitoring is needed to ensure the safety of food intake and dietary patterns among vulnerable groups in Korea.

Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.

Flavonoids are polyphenolic compounds that are present in plants. They have been shown to possess a variety of biological activities at non-toxic concentrations in organisms. Galangin, a member of the flavonol class of flavonoid, is present in high concentrations in medicinal plants (e.g. Alpinia officinarum) and propolis, a natural beehive product. Results from in vitro and in vivo studies indicate that galangin with anti-oxidative and free radical scavenging activities is capable of modulating enzyme activities and suppressing the genotoxicity of chemicals. These activities will be discussed in this review. Based on our review, galangin may be a promising candidate for cancer chemoprevention.

Activated p56lck directs maturation of both CD4 and CD8 single-positive thymocytes.

p56(lck) is a protein tyrosine kinase expressed throughout T cell development. It associates noncovalently with the cytoplasmic domains of the CD4 and CD8 coreceptor molecules and has been implicated in TCR signaling in mature T cells. Its role in early thymocyte differentiation has been demonstrated in vivo, both by targeted gene disruption and by transgene expression. Previously, we showed that expression of a dominant-negative form of p56(lck) in double-positive thymocytes inhibits positive selection. We now demonstrate that expression of constitutively activated p56(lck) (p56(lck)F505) accelerates the transition from the double-positive to the single-positive stage. Importantly, p56(lck)F505 drives survival and lineage commitment of thymocytes in the absence of TCR engagement by appropriate MHC molecules. These results indicate that activation of p56(lck) constitutes an early step in conveying maturational signals after TCR ligation by a positively selecting ligand. Our study provides direct in vivo evidence for the role of p56(lck) in regulating TCR signaling.

Lck activity controls CD4/CD8 T cell lineage commitment.

Thymocytes carrying MHC class I-restricted TCRs differentiate into CD8 T cells, while those recognizing MHC class II become CD4 T cells. The mechanisms underlying how MHC class recognition, coreceptor expression, and effector function are coordinated are not well understood. Since the tyrosine kinase Lck binds with more affinity to CD4 than CD8, it has been proposed as a candidate to mediate this process. By using transgenic mice with altered Lck activity, we show that thymocytes carrying a class II-restricted TCR develop into functional CD8 T cells when Lck activity is reduced. Conversely, thymocytes carrying a class I-restricted TCR develop into functional CD4 T cells when Lck activity is increased. These results directly show that quantitative differences in the Lck signal control the CD4/CD8 lineage decision.

Antigenotoxicity of galangin against N-methyl-N-nitrosourea.

Using the Ames bacterial mutagenicity test and an in vivo micronucleus test, we investigated the antigenotoxic effect of galangin against the genotoxicity of N-methyl-N-nitrosourea (MNU). In the Ames assay, galangin showed an antimutagenic effect towards MNU-induced mutagenicity of Salmonella typhimurium TA 100. In mice, galangin showed an anticlastogenic effect against MNU-induced micronuclei in polychromatic erythrocytes in the MNPCE in mouse bone marrow cells. On the other hand, galangin is neither mutagenic nor clastogenic in both assays. Results from our in vitro and in vivo studies indicate that galangin is capable of suppressing the mutagenicity and clastogenicity of MNU. Therefore, galangin may be a useful chemopreventive agent against potential long-term health effects from genotoxic environmental agents.

Requirement for Jak3 in mature T cells: its role in regulation of T cell homeostasis.

The tyrosine kinase Jak3 plays a key role in transducing signals from the IL-2, -4, -7, -9, and -15 receptors. Mice lacking Jak3 exhibit a profound, early block in both B and T cell development. To examine the mechanisms whereby Jak3 influences T cell function, we have reconstituted thymic development in Jak3-/- animals by introducing a Jak3 transgene in which expression was driven by the lck proximal promoter. Thymic reconstitution required Jak3 kinase activity, as catalytically inactive Jak3 did not restore early thymic development. Furthermore, the thymus-restricted expression pattern of the transgene allowed us to assess the requirement for Jak3 in peripheral T cells. In these mice, loss of Jak3 expression was associated with a failure to proliferate in response to antigen receptor crosslinking, the accumulation of T cells manifesting an activated cell surface phenotype, and an increased CD4/CD8 ratio among peripheral T cells, all of which are characteristics that were observed in Jak3-/- animals. Finally, we present data which suggest that peripheral T cells proliferate more rapidly in vivo and also undergo apoptosis more rapidly, upon loss of Jak3. Hence Jak3 exerts effects on mature peripheral T lymphocytes, as well as on thymocytes, resulting in the proper maintenance of circulating, quiescent cells.

Abnormal morphological patterns of the left ventricular myocardium in the critical stenosis of the aortic valve and the intact ventricular septum.

The evaluation of prognostic factors in infants with critical stenosis of the aortic valve and intact ventricular septum is often misleading due to a complex interaction among lesions in the mitral and aortic valves, and the left ventricular myocardium. The clinical parameters on the left ventricular function, such as ejection fraction and left ventricular end-diastolic volume, are of particular interest as their effects on survival are very controversial. We performed a clinicopathologic analysis of two autopsied cases of this disease. Besides the morphological hallmarks of the aortic and mitral valves, these two cases showed two extreme types of pathology in the left ventricular myocardium, which might have significant impacts on the clinical evaluation of the left ventricular function. Case 1 showed endocardial fibroelastosis associated with abnormal intertrabecular spaces (so-called spongy myocardium), obscuring accurate estimation of the left ventricular end-diastolic volume. Case 2 showed ischemic necrosis of the apical part of the left ventricular myocardium. This infarct was associated with acute and chronic subendocardial ischemia and mild endocardial fibroelastosis. Aggravation of the left ventricular failure could be caused by the recent ischemic insult. The evaluation of the left ventricular function, therefore, should include the evaluation of the morphologic status of the myocardium as regards to whether there is ischemia, endocardial fibroelastosis or hypertrophied trabeculae in addition to stenotic lesions in the aortic and mitral valves.

Aneurysmal dilatation of ascending aorta and aortic insufficiency in juvenile spondyloarthropathy.

Aortic insufficiency is a well-recognized complication of adult spondyloarthropathy but rare in juveniles, and no report is associated with aneurysmal dilatation at any age. We describe rapidly progressive aortic insufficiency with aneurysmal dilatation of ascending aorta in a 15-year-old boy with juvenile spondyloarthropathy, necessitating a Bentall operation.

Requirement for p56lck tyrosine kinase activation in T cell receptor-mediated thymic selection.

The nonreceptor protein tyrosine kinase p56lck (Lck) serves as a fundamental regulator of thymocyte development by delivering signals from the pre-T cell receptor (pre-TCR) that permit subsequent maturation. However, considerable evidence supports the view that Lck also participates in signal transduction from the mature TCR. We have tested this conjecture by expressing a dominant-negative form of Lck under the control of a promoter element (the distal lck promoter) that directs high expression in CD4+CD8+ thymocytes, mature thymocytes, and peripheral T cells, thereby avoiding, complications that result from the well-documented ability of dominant-negative Lck to block very early events in thymocyte maturation. Here we report that expression of the catalytically inactive Lck protein at twice normal concentrations inhibits thymocyte positive selection by as much as 80%, while leaving other aspects of cell maturation intact. This effect was studied in more detail in mice simultaneously bearing the male-specific H-Y alpha/beta TCR transgene and ovalbumin-specific DO10 alpha/beta TCR transgene, where even equimolar expression of the dominant-negative Lck protein substantially vitiated the positive selection process. Although deletion of H-Y alpha/beta thymocytes proceeded normally in male mice despite the presence of catalytically inactive Lck, modest inhibition of superantigen-mediated deletion was in some cases observed. These data further implicate Lck in the propagation of all TCR-derived signals, and indicate that even very modest deficiencies in the representation of functional Lck molecules could in humans, profoundly alter the character of the peripheral TCR repertoire.

An Epstein-Barr virus-associated lymphoproliferative lesion of the skin presenting as recurrent necrotic papulovesicles of the face.

We describe four patients with lymphoproliferative lesions confined to the skin for several years. They presented with recurrent necrotic papulovesicles of the face. Latent Epstein-Barr virus (EBV) infection was detected in the lymphoid cells from the skin lesions by in situ hybridization. The disease in three patients progressed to T-cell lymphoma. We believe that these patients represent a subset of peripheral T-cell lymphoma with a tendency to localize in the skin.

Behçet's disease with Sweet's syndrome-like presentation--a report of six cases.

We describe six cases of Behcet's disease, which showed Sweet's syndrome-like features. The clinical findings in our patients closely resemble those of the cases described in previous reports on Sweet's syndrome. However, oral and genital mucosal involvement, non-tenderness of the lesions and a pustular eruption elsewhere made us consider Behçet's disease. Besides the clinical findings, vasculitis was clearly demonstrated in the skin biopsy specimens.