Maternal-to-fetus transfer of mercury in metallothionein-null pregnant mice after exposure to mercury vapor

This study examined the role of placenta metallothionein (MT) in maternal-to-fetal mercury transfer in MT-null and wild-type mice after exposure to elemental mercury (Hg(0)) vapor. Both strains were exposed to Hg(0) vapor at 5.5-6.7 mg/m(3) for 3 h during late gestation. Twenty-four hours after exposure to Hg(0) vapor, accumulation of mercury in the major organs, except the brain, of MT-null maternal mice was significantly lower than that in organs of wild-type mice. In contrast to mercury levels in maternal organs, fetal mercury levels were significantly higher in MT-null mice than in wild-type mice. In placenta, mercury concentrations were not significantly different between the two strains. Although MT levels in major organs, except the brain, of wild type mice were markedly elevated after the exposure to Hg(0) vapor, the placental MT levels were not elevated. However, endogenous MT level in the placenta is significantly higher than that in other organs, except the liver. Gel filtration profile of the placental cytosol in the wild-type mice revealed that a large amount of placental mercury was associated with MT. In MT-null mice, mercury in placental cytosol appeared mainly in the high-molecular-weight protein fractions. Mercury in the placenta was localized mainly in the yolk sac and decidual cells in the deep layer of the decidua in both mouse strains. The similar localization of MT was found in the placenta of wild type mice. These results suggest that MT in the placenta has a defensive role in preventing maternal-to-fetal mercury transfer.     

Effects of the Chinese herbal medicines Bupleuri radix, Ginseng radix, and Zingiberis rhizoma on lymphatic vessel activity in rats

The aim of the present study was to determine the effects of the Chinese herbal medicines Bupleuri radix, Ginseng radix and Zingiberis rhizoma on spontaneous lymphatic vessel activity. The effect of each herbal medicine on in vivo lymphatic flow was examined by injection of dye into the femoral regions of rats after feeding with the herbal medicines. In an in vitro study, spontaneous changes in diameter of the rat thoracic duct were monitored, and each segment was exposed to each herbal medicine. In the in vivo study, 100% of the right iliac lymphatic node were positively stained in the herbal medicine group, whereas only 40% of the node were positively stained in the control group. In the in vitro study, Bupleuri radix and Ginseng radix increased the amplitude of spontaneous activity of lymphatic vessels in a concentration-dependent manner with or without L-NAME, an NO synthase inhibitor. The results indicated that the herbal medicines Bupleuri radix and Ginseng radix activated spontaneous lymphatic vasomotion and lymph flow, and the mechanisms of this effect seem to be independent of endothelial cells.     

AAV1/2-mediated CNS Gene Delivery of Dominant-negative CCL2 Mutant Suppresses Gliosis, ��-amyloidosis, and Learning Impairment of APP/PS1 Mice

Accumulation of aggregated amyloid-β (Aβ) peptide was studied as an initial step for Alzheimer''s disease (AD) pathogenesis. Following amyloid plaque formation, reactive microglia and astrocytes accumulate around plaques and cause neuroinflammation. Here brain chemokines play a major role for the glial accumulation. We have previously shown that transgenic overexpression of chemokine CCL2 in the brain results in increased microglial accumulation and diffuse amyloid plaque deposition in a transgenic mouse model of AD expressing Swedish amyloid precursor protein (APP) mutant. Here, we report that adeno-associated virus (AAV) serotype 1 and 2 hybrid efficiently deliver 7ND gene, a dominant-negative CCL2 mutant, in a dose–response manner and express >1,000-fold higher recombinant CCL2 than basal levels after a single administration. AAV1/2 hybrid virus principally infected neurons without neuroinflammation with sustained expression for 6-months. 7ND expressed in APP/presenilin-1 (APP/PS1) bigenic mice reduced astro/microgliosis, β-amyloidosis, including suppression of both fibrillar and oligomer Aβ accumulation, and improved spatial learning. Our data support the idea that the AAV1/2 system is a useful tool for CNS gene delivery, and suppression of CCL2 may be a therapeutic target for the amelioration of AD-related neuroinflammation.     

Marginal Zone B-cell Lymphoma Arising from Buccal Mucosa Resembling Inflammatory Myofibroblastic Tumor of the Soft Tissue

We report here a case of marginal zone B-cell lymphoma (MZBL) arising from buccal mucosa resembling inflammatory myofibroblastic tumor (IMT) of the soft tissue. On a low-power field, the lesion is characterized by fibrous granulation tissue and numerous lymphoid follicles with or without atrophic small germinal center. A portion of the lymphoid follicles were surrounded by partial and/or complete thin pale cuff of centrocyte-like (CCL) cells on high power field. The thin rim of the lymphoid follicles contained CCL-cells, plasma cells, cells showing plasma cell differentiation and mature eosinophils. In contrast, the granulomatous areas contained were characterized by haphazardly arranged spindle cells, mature plasma cells, mature eosinophils, small-to-medium lymphocytes and histiocytes. Histologically, IMT was suspected. However, flow cytometry and immunohistochemical study demonstrated a monotypic nature of centrocyte-like cells, plasma cells and their precursor and confirmed the diagnosis of MZBL arising from the buccal mucosa. The differential diagnostic problems between IMT of the soft tissue and classical Hodgkin lymphoma and T-cell lymphoma have been discussed previously. However, the present case indicated that MZBL should be added to the differential diagnosis of IMT of the soft tissue.