A novel genotype of beak and feather disease virus in budgerigars (<Emphasis Type="Italic">Melopsittacus undulatus</Emphasis>)

House sparrow (Passer domesticus) is one of the most widely distributed wild birds in China. Five Newcastle disease virus (NDV) strains were isolated from house sparrows living around the poultry farms in southern China. These isolates were characterized by pathogenic assays and phylogenetic analysis. The results showed that all NDV isolates except one were velogenic and virulent for chickens. These four virulent strains for chickens possess the amino acid sequence ¹¹²R/K-R-Q-K/R-R-F¹¹⁷ in the F₀ cleavage site which is typical of velogenic NDV. Phylogenetic analysis indicated that these isolates belong to genotype VII and were closely related to the strains which were isolated from NDV outbreaks in chickens since 2000. One isolate of NDV from house sparrow belong to genotype II and was proved to be vaccine strain (Chicken/U.S./LaSota/46). The result of this study proved that house sparrow can carry the virulent NDV strains and the same genotype of viruses that are circulating in poultry are existing in house sparrows living around poultry farm in southern China.     

Atypical soft tissue perineurioma in the tongue of a young girl

Perineuriomas are uncommon benign peripheral nerve sheath tumors that include soft tissue, sclerosing, reticular, and intraneural variants. Soft tissue perineuriomas arise in a wide anatomic distribution and mostly in patients older than 20 years of age. We report an atypical perineurioma in a 7-year-old girl. The tumor, located in the tongue, was uniformly hypercellular. The tumor cells were spindle-shaped with a slender, elongated, bipolar, wavy cytoplasmic process formation and wavy elongated nuclei, and the architecture was composed of predominantly short fascicles with areas exhibiting a vague storiform pattern. Although the tumor cells generally appeared bland, the tumor showed worrisome features including an infiltrative pattern and occasional mitotic figures. Psammoma bodies were observed in the periphery of the tumor. Immunohistochemically, the cells were positive for epithelial membrane antigen, vimentin, claudin-1, and GLUT-1, but negative for S-100 protein, CD34, and type IV collagen. The authors document a case of soft tissue perineurioma with atypical histological features that occurred in the tongue of a child.     

Robust HIV-specific immune responses were induced by DNA vaccine prime followed by attenuated recombinant vaccinia virus (LC16m8 strain) boost

Recombinant vaccinia virus-based vaccine combined with DNA vaccine has produced a protective immune response against HIV infection in non-human primates. In this study, we explored the immunogenicity of a recombinant vaccinia virus (LC16m8 strain), which has been used in children without severe side effects. The vaccinia virus expressing an HIV(89.6)env gene (vLC-Env) alone or combined with a DNA vaccine expressing the HIV(89.6)env gene (pCAG-Env) was characterized in BALB/c mice. Vaccination of vLC-Env induced much higher HIV-specific humoral and cell-mediated immune responses than that of pCAG-Env. Priming with pCAG-Env further enhanced vLC-Env induced immune responses, especially cell-mediated immune response. Moreover, efficient expression of Env protein was achieved following infection of bone marrow dendritic cells by vLC-Env in vitro. Administration of vLC-Env-infected dendritic cells to mice generated a high cell-mediated immune response. These results demonstrate that priming with pCAG-Env and boosting with vLC-Env represents a logical candidate for vaccination against HIV infection.     

The effects of preceding moving stimuli on the initial part of smooth pursuit eye movement

We examined whether there are any adaptive effects on the pursuit initiation after a prolonged exposure to moving visual stimuli. The eye movements of six human subjects were recorded with the scleral search-coil technique or a Dual Purkinje Image Eye-tracker system. A random-dot image appeared on a CRT monitor and moved coherently in one direction (rightward or leftward) at 10 deg/s for 4 s, while the subject fixated on a stationary target (conditioning stimulus). The screen was blanked for 0.2 s, and then the target stepped to the right or left of the center and moved 10 deg/s leftward or rightward. We measured change in the eye position over the open-loop period of the pursuit initiation. When the pursuit target moved in the same direction as the preceding visual stimulus, a significant reduction in the initial tracking responses (55.9% decrease on average) was found. We then studied in detail the properties of the motion adaptation in pursuit initiation by varying the visual conditions systematically and obtained the following findings. When the subjects tracked the target that moved at 10 deg/s, the pursuit initiation was affected not only by the conditioning stimulus of the same speed as the target, but also by those of different speeds. Further, the conditioning stimulus moving at 10 deg/s affected the pursuit initiation not only when the target moved with the same speed but also when it moved at different speeds (more remarkable for slower speeds). The effect of conditioning stimuli on the pursuit initiation was larger when the duration of the conditioning period was longer. The effect of conditioning stimuli decayed as the duration of the blank period became longer. The findings from the present study are consistent with the properties of neurons in the middle temporal area of monkeys.     

Histamine H1 receptor-stimulated interleukin 8 and granulocyte macrophage colony-stimulating factor production by bronchial epithelial cells requires extracellular signal-regulated kinase signaling via protein kinase C

BACKGROUND: Histamine stimulates the release of several cytokines, such as interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor, from bronchial epithelial cells. However, the functional individual histamine receptor subtype and intracellular signaling in bronchial epithelial cells are poorly defined. METHODS: Using human primary epithelial cells and the NCI-H292 cell line, we examined the expression of histamine receptor subtypes and histamine-induced second messenger. We also evaluated the involvements of mitogen-activated protein kinase, protein kinase C (PKC) and epidermal growth factor receptor in cytokine expression caused by histamine. RESULTS: Histamine H1 receptor (H1R) was the only subtype expressed in both types of cells. Histamine elevated intracellular calcium ion without affecting cAMP levels. Histamine induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Histamine also phosphorylated PKC and myristoylated alanine-rich C kinase substrate. Ro-31-8220, a PKC inhibitor, and PD98059, a mitogen-activated protein/ERK kinase inhibitor, suppressed the histamine-induced ERK activation and the production of granulocyte macrophage colony-stimulating factor and IL-8. On the contrary, histamine had no effect on the phosphorylation of epidermal growth factor receptor, and its specific inhibitor AG1478 failed to inhibit the histamine-induced ERK activation. Olopatadine, an H1 antagonist, completely blocked the histamine-related responses, whereas H2 and H3 antagonists did not. Histamine also augmented the IL-8 production caused by IL-4 or tumor necrosis factor-alpha. CONCLUSIONS: The H1R-PKC-ERK pathway may play crucial roles in eliciting cytokine production from bronchial epithelial cells stimulated by histamine, leading to airway inflammation.     

Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C

In a single hospital in Tokyo, the 87 patients infected persistently with hepatitis B virus (HBV) genotype A, the 413 with B, and the 3,389 with C were compared for virological outcome. Hepatitis B surface antigen (HBsAg) was cleared from the serum in 12% (3/26), 2% (2/112), and 3% (23/826) of patients with genotypes A, B, and C, respectively, at 5 years of follow-up (P = 0.0395). Hepatitis B e antigen (HBeAg) was cleared from serum more frequently in patients with genotype B than those with A or C (78% [32/41] vs. 58% [11/19] or 45% [251/562], P = 0.00001) at 5 years. Of the 45 individuals infected with genotype A and followed for 3 years or longer, HBeAg was more frequent (16% [3/19] vs. 73% [19/26], P = 0.0002) and levels of HBV DNA higher (median <2.6 [range: <2.6-5.6] vs. >7.6 [<2.6->7.6] log copies/ml, P = 0.001) in the 26 patients with biopsy-proven chronic hepatitis than the 19 asymptomatic carriers. Among the 26 hepatitis patients infected with HBV genotype A, decreases in HBV DNA were less frequent (20% [1/5] vs. 93% [13/14] or 86% [6/7], P = 0.0095) and increases in serum levels of hyaluronic acid > or =10 ng/ml commoner (80% [4/5] vs. 14% [2/14] or 14% [1/7], P = 0.017) in the patients who kept HBeAg than in those who seroconverted or who remained HBeAg-negative. In conclusion, patients persistently infected with HBV genotype A fare better than those with genotype B or C. However, high levels of HBV DNA continue in those in whom HBeAg persists along with fibrosis in the liver.     

A case of acute myelogenous leukemia with MLL-AF10 fusion caused by insertion of 5' MLL into 10p12, with concurrent 3' MLL deletion

Structural abnormalities involving the mixed-lineage leukemia (MLL) gene on 11q23 have been associated with hematological malignancies. The rearrangement of MLL occurs during translocations and insertions involving a variety of genes on the partner chromosome. We report a rare case of acute myelogenous leukemia (AML-M2) with 11q23 abnormalities. Fluorescence in situ hybridization (FISH) using a commercial dual-color MLL probe detected an atypical signal pattern: one fusion signal, two green signals smaller than those usually detected, and no orange signals. Spectral karyotyping (SKY) analysis indicated that one green signal was detected on the short arm of derivative chromosome 10, and the other green signal on the long arm of a derivative chromosome 11, on which no orange signal was detected. A long-distance inverse polymerase chain reaction (LDI-PCR) identified the fusion partner gene, in which intron 6 of MLL was fused with intron 8 of AF10 on 10p12 in the 5' to 3' direction. Our observations indicated that the MLL-AF10 fusion gene resulted from the insertion of part of the region that included the 5' MLL insertion into 10p12; this was concurrent with the deletion of 3' MLL.     

Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus

Circulation of mature lymphocytes between blood and secondary lymphoid tissues plays a central role in the immune system. Homing of lymphocytes from blood into secondary lymphoid tissues beyond high endothelial venules is highly dependent on the interaction between the chemokines CCL19, CCL21, CXCL12, and CXCL13, and their receptors CCR7, CXCR4 and CXCR5. However, the molecular mechanism（s） of lymphocyte egress from secondary lymphoid tissues to lymph remained unclear. We have found a new class of immunomodulator, FTY720 by chemical modification of vegetative wasp-derived natural product, ISP-I （myriocin）. FTY720 has been shown to be highly effective in experimental allograft and autoimmune disease models. A striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunomodulating activity in these models. The reduction of circulating lymphocytes by FTY720 is caused by sequestration of lymphocytes into secondary lymphoid tissues and thymus. FTY720 is rapidly converted to （S）-enantiomer of FTY720-phosphate [（S）-FTY720-P] by sphingosine kinase 2 in vivo. （S）-FTY720-P acting as a potent agonist of S1P receptor type 1 （S1P1）, induces long-term down-regulation of S1P1 on lymphocytes, and thereby inhibits the migration of lymphocytes toward S1P. Thus, it is presumed that FTY720-induced lymphocyte sequestration is due to the inhibition of S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus by its active metabolite （S）-FTY720-P. Throughout the analysis of the mechanism of action of FTY720, it is clarified that S1P/S1P1 interaction plays an important role for lymphocyte egress from secondary lymphoid tissues and thymus.     

Induction of long-term lipopolysaccharide tolerance by an agonistic monoclonal antibody to the toll-like receptor 4/MD-2 complex

We have established an agonistic monoclonal antibody, UT12, that induces stimulatory signals comparable to those induced by lipopolysaccharide (LPS) through Toll-like receptor 4 and MD-2. UT12 activated nuclear factor kappaB and induced the production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in peritoneal exudative cells. In addition, mice injected with UT12 rapidly fell into endotoxin shock concomitant with the augmentation of serum TNF-alpha and IL-6 levels, followed by death within 12 h. On the other hand, when the mice were pretreated with a sublethal dose of UT12, the mice survived the subsequent lethal LPS challenges, with significant suppression of serum TNF-alpha and IL-6, indicating that UT12 induced tolerance against LPS. This effect of UT12 was maintained for at least 9 days. In contrast, the tolerance induced by LPS continued for less than 3 days. These results illuminate a novel potential therapeutic strategy for endotoxin shock by the use of monoclonal antibodies against the Toll-like receptor 4/MD-2 complex.     

Mast cell-derived tumor necrosis factor can promote nerve fiber elongation in the skin during contact hypersensitivity in mice

In humans, lesions of contact eczema or atopic dermatitis can exhibit increases in epidermal nerves, but the mechanism resulting in such nerve elongation are not fully understood. We found that contact hypersensitivity reactions to oxazolone in mice were associated with significant increases in the length of nerves in the epidermis and dermis. Using genetically mast cell-deficient c-kit mutant mice selectively repaired of their dermal mast cell deficiency with either wild-type or tumor necrosis factor (TNF)-deficient mast cells, we found that mast cells, and mast cell-derived TNF, significantly contributed to the elongation of epidermal and dermal PGP 9.5+ nerves and dermal CGRP+ nerves, as well as to the inflammation observed at sites of contact hypersensitivity in response to oxazolone. Moreover, the percentage of mast cells in close proximity to dermal PGP 9.5+ nerve fibers was significantly higher in wild-type mice and in c-kit mutant mice repaired of their dermal mast cell deficiency by the adoptive transfer of wild-type mast cells than in TNF-deficient mice or in TNF-/- mast cell-engrafted c-kit mutant mice. These observations show that mast cells, and mast cell-derived TNF, can promote the elongation of cutaneous nerve fibers during contact hypersensitivity in the mouse.