Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis

To determine whether the EBV genome content in serum or plasma reflects clinical features and outcome in EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), we quantified the cell-free EBV genome copy number by real-time PCR in 38 patients with EBV-HLH, and compared this to the values from 15 patients with infectious mononucleosis (IM). The median (range) cell-free EBV genome copy number at diagnosis was 3.0 x 10(3) (undetectable -5.5 x 10(7)) copies/ml in EBV-HLH, which was significantly higher than the 6.6 x 10(1) (undetectable -1.0 x 10(3)) copies/ml in IM (P = 0.0008). We serially analyzed cell-free EBV genome copy number in 10 cases of EBV-HLH up to 4 months from diagnosis. In four patients who achieved remission, the EBV genome became undetectable soon after starting therapy. In the remaining six patients who responded poorly to therapy, the EBV genome copy number in the serum or plasma remained at high levels except for one case. In addition, we confirmed that the EBV genome became undetectable after hematopoietic stem cell transplantation in 4 EBV-HLH cases. These results suggest that the quantitative analysis of cell-free EBV genome copy number is useful for evaluating disease activity and for predicting the response to therapy in EBV-HLH.     

Increase in T cells bearing the gamma/delta receptor associated with lymphoproliferative disease of granular lymphocytes in an infant with intractable diarrhea

A two-year-old infant with intractable diarrhea and lymphoproliferative disease of granular lymphocytes attributed to a persistent cytomegalovirus infection showed an increase in cells bearing the gamma/delta T-cell receptor (TCR), which accounted for approximately 20% of total peripheral blood lymphocytes and 40% of CD3+ T cells. Of the gamma/delta TCR+ cells, two-thirds were double negative (CD4–/CD8–) and the other one-third CD8 positive. The majority of gamma/ delta + cells were delta TCS 1 positive. The predominance of delta TCS 1 positive cells was also confirmed on biopsy of lymphoid tissues from the colon. After improvement of watery diarrhea and malnutrition following three-month hyperalimentation, the number of gamma/delta TCR+ cells decreased. The patient subsequently died of pneumonia at the age of 2 years and 11 months. A possible site-specific role for the gamma/delta TCR + cells, particularly delta TCS 1 + cells, in the human intestine is discussed.     

Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12

Interleukin (IL)-12 is a key factor for inducing cellular immune responses, which play a central role in the eradication of cancer. In the present study, in order to create a dendritic cell (DC)-based vaccine capable of positively skewing immune response toward a cellular immunity-dominant state, we analyzed immunological characteristics and vaccine efficacy of DCs cotransduced with melanoma-associated antigen (gp100) and IL-12 gene (gp100+IL12/DCs) by using RGD fiber-mutant adenovirus vector (AdRGD), which enables highly efficient gene transduction into DCs. gp100+IL12/DCs could simultaneously express cytoplasmic gp100 and secretory IL-12 at levels comparable to DCs transduced with each gene alone. In comparison with DCs transduced with gp100 alone (gp100/DCs), upregulation of major histocompatibility complex class I, CD40, and CD86 molecules on the cell surface and more potent T-cell-stimulating ability for proliferation and interferon-gamma secretion were observed as characteristic changes in gp100+IL12/DCs. In addition, administration of gp100+IL12/DCs, which were prepared by a relatively low dose of AdRGD-IL12, could induce more potent tumor-specific cellular immunity in the murine B16BL6 melanoma model than vaccination with gp100/DCs. However, antitumor effect and B16BL6-specific cytotoxic T-lymphocyte activity in mice vaccinated with gp100+IL12/DCs diminished with increasing AdRGD-IL12 dose during gene transduction, and paralleled the decrease in presentation levels via MHC class I molecules for antigen transduced with another AdRGD. Collectively, our results suggested that optimization of combined vector dose was required for development of a more efficacious DC-based vaccine for cancer immunotherapy, which relied on genetic engineering to simultaneously express tumor-associated antigen and IL-12.     

Effects of 17beta-estradiol on chemically induced long-term depression

In this study, we have investigated the effects of 17beta-estradiol (E2) on chemically induced long-term depression (LTD). LTD was induced by a brief application of N-methyl-D-aspartate (NMDA) or (R,S)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor agonist. Bath application of E2 alone potentiated population excitatory postsynaptic potentials. This potentiation was readily reversed by washing with control saline. The effect of E2 on NMDA-induced LTD was a conversion of LTD to long-term potentiation (LTP). An application of NMDA in the presence of E2 induced LTP. The induction of LTP was inhibited by an inhibitor of calcium/calmodulin dependent protein kinase (CaMKII). The results suggest that E2 potentiates NMDA receptor function and induces an increase in postsynaptic Ca2+ concentration. An increase in postsynaptic Ca2+ concentration activates CaMKII, leading to LTP. In contrast to NMDA-induced LTD, an application of DHPG in the presence of E2 induced significantly larger LTD. The results suggest that E2 potentiates an as yet unidentified process(es) in inducing LTD by an application of DHPG. The effects of E2 both on NMDA-induced and DHPG-induced LTD were suppressed by an estrogen receptor antagonist.     

Dietary patterns and colorectal adenomas in Japanese men: the Self-Defense Forces Health Study

The role of dietary patterns in colorectal carcinogenesis remains unclear in Asian populations. Using 1999-2002 data, the authors investigated the association between dietary patterns and colorectal adenomas in 1,341 Japanese men who underwent total colonoscopy. Information about diet was obtained using a 74-item food frequency questionnaire prior to the colonoscopy. Three dietary patterns were generated by factor analysis: 1) a high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; 2) an "animal food" pattern; and 3) a Japanese pattern. Logistic regression analysis was used to estimate the odds ratio of having colorectal adenomas with the adjustment for potential confounding variables including body mass index, smoking, alcohol, and leisure-time physical activities. A significant inverse association was found for the high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; the odds ratios for the second, third, and fourth quartiles were 0.97 (95% confidence interval: 0.70, 1.36), 0.71 (95% confidence interval: 0.50, 1.01), and 0.62 (95% confidence interval: 0.43, 0.90), respectively, compared with the lowest (p(trend) = 0.003). Similar associations were observed for larger adenomas or for each subsite of the colorectum. The Japanese and "animal food" patterns were not clearly associated with colorectal adenomas. A dietary pattern including greater consumption of dairy products and fruits and vegetables with low alcohol consumption may be associated with decreased risk of colorectal adenomas.