Serum Concentrations of Eosinophil Cationic Protein and Eosinophils of Patients with Kimura's Disease

ABSTRACTBackground: To clarify the role of eosinophils in the pathogenesis of Kimura's disease and the values of measuring serum levels of eosinophil cationic protein (ECP) for monitoring disease activity might be very important, but there are few reports about this matter.Methods: A total 14 serum and 7 tissue samples from patients with Kimura's disease were studied. The concentrations of ECP and cytokines (interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 5 (IL-5)) in sera from patients with Kimura's disease were measured by enzyme-linked immunosorbent assay (ELISA). The density of eosinophils and the degree of activation of eosinophils in the tissue were also studied immunohistochemically.Results: The concentration of ECP in sera from patients with Kimura's disease was significantly higher than that in the control group (p<0.05). At the time of the remission, a significant decrease of ECP was observed. In interfollicular areas, most infiltrated eosinophils were positive for EG2 antibody (64.0-94.0%) and the mean percentage of EG2-positive eosinophils was 75.7%. The concentrations of IL-4, gM-CSF, and IL-5 in sera from patients with Kimura's disease were within normal ranges or below the detectable level in all sera examined.Conclusions: Our findings suggest that eosinophils play an important role in the pathogenesis of Kimura's disease and ECP may be used as an additional parameter of disease activity

Small sensor probe for measuring plasma waves in space Space science

Background: Since conventional one-point observations of plasma phenomena in space cannot distinguish between time and spatial variations, the missions on the basis of multiple-point observations have become the trend. We propose a new system for multiple-point observation referred to as the monitor system for space electromagnetic environments (MSEE). Findings: The MSEE consists of small sensor probes that have a capability to measure electromagnetic waves and transfer received data to the central station through wireless communication. We developed the prototype model of the MSEE sensor probe. The sensor probe includes a plasma wave receiver, the microcontroller, the wireless communication module, and the battery in the 75-mm cubic housing. In addition, loop antennas, dipole antennas, and actuators that are used for expanding dipole antennas are attached on the housing. The whole mass of the sensor probe is 692 g, and the total power consumption is 462 mW. The sensor probe can work with both inner battery and external power supply. The maximum continuous operation time on battery power is more than 6 h. We verified the total performance for electric field measurements by inputting signal to preamplifier. In this test, we found that analog components had enough characteristics to measure electric fields, and the A/D conversion and the wireless transmission worked correctly. In the whole performance for electric fields, the sensor probe has equivalent noise level of - 135 dBV/m/√Hz. Conclusions: We succeed in developing the prototype model of the small sensor probe that had enough sensitivity for electric field to measure plasma waves and the ability to transfer observation data through wireless communication. The success in developing the small sensor probe for the measurement of plasma waves leads to the realization of the multiple-point observations using a lot of small probes scattered in space

Significant effect of polymorphisms in CYP2D6 and ABCC2 on clinical outcomes of adjuvant tamoxifen therapy for breast cancer patients

Purpose The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen. Patients and Methods We studied 282 patients with hormone receptor–positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d. Results CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with ≤ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups. Conclusion Our results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen

High viral load of Merkel cell polyomavirus DNA sequences in Langerhans cell sarcoma tissues.

International audienceBACKGROUND: Langerhans cell (LC) sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytologic features and an LC phenotype. We very recently suggested that LC behaves as a reservoir for common dermotropic Merkel cell polyomavirus (MCPyV) and determined the relationship between LC histiocytosis (LCH), which has an underlining oncogenic capacity, and MCPyV as a trigger for a reactive process rather than a neoplastic process. We propose LC to be a reservoir for MCPyV and hypothesize that some LCS subtypes may be related to the MCPyV agent. FINDINGS: We examined seven LCS tissues using multiplex quantitative PCR (Q-PCR) and immunohistochemistry with anti MCPyV large-T (LT) antigen antibody. High viral loads of MCPyV DNA sequences (viral load = relative levels of MCPyV) were detected (0.328-0.772 copies/cell (Merkel cell carcinoma (MCC) = 1.0)) using Q-PCR in 43% (3/7) tissues, but LT antigen expression was not observed (0/7). CONCLUSIONS: Frequent MCPyV-DNA amplification suggests that LCS in some patients may be related to MCPyV infection. Moreover, the higher viral load of LCS (median, 0.453 copies/cell) than low load of LCH (0.003, median of 12 cases) (P < 0.01) may suggest a virally induced tumorigenic process in some LCS. Although the absence of LT antigen expression may indicate a different role for MCPyV in this pathology, some subtypes of LCS may develop in the background of MCPyV-infected LC. To the best of our knowledge, this is the first report on the relationship between MCPyV and LCS. The recent discovery of MCPyV opened new therapeutic avenues for MCC. These data open novel possibilities for therapeutic interventions against LCS

Development of follicular dendritic cells: A study using short-term bone marrow cell grafting in SCID mice

To evaluate the cellular origin of follicular dendritic cells (FDC) in lymphoid follicles (LFs), severe combined immunodeficient (SCID) mice (H-2d) were grafted with 5-bromo-2'-deoxyuridine (BrdU)- incorporated bone marrow cells from CB-17 mice (H-2'9 and with non-BrdU-incorporated bone marrow cells from C3H mice (H-2k) and Wistar rats (RTIU). This procedure was followed by antigenic stimulation with horseradish peroxidase and related immune complex (mouse peroxidase anti-peroxidase) administration. Secondary LFs in the lymph nodes and spleen of the reconstructed SCID mice were examined morphologically and immunocytochemically. LFs reconstructed with CB-17 mouse bone marrow cells contained FDCs capable of trapping and/or retaining mouse peroxidase anti-peroxidase as immune complexes. Secondary LFs contained BrdU-incorporated germinal center lymphocytes but not non-lymphoid stromal cells. A cell grafting study in SCID mice using bone marrow cells from C3H mice and Wistar rats demonstrated that FDCs in reconstructed LFs exhibited a marker specific for the recipient but not for the donor. These data indicate that functionally active FDCs occur de novo in reconstructed LFs in SCID mice, and do not support the view that FDCs originate from bone marrow cells in short-term reconstructed LFs

The lymphocyte-dendritic cell system

Antigens provoke immune responses. The group of immunocompetent cells related directly to this response includes T and B cells, macrophages (MO) and dendritic cells (DCs). DCs acting as antigen-presenting cells have been recently recognized to be important in initiating the immune response. B cells and follicular dendritic cells (FDCs), the major immunocompetent cells in the B-cell dependent area, play an important role in humoral immunity, while T cells and interdigitating cells (IDCs), which are the major immunocompetent cells in the T-cell dependent (TD)-area, play an important role in cellular immunity. The B cell-IDC interaction in the TD-area is also essential for the B-cell response against TD-antigen. Consequently, the lymphocyte-DC interaction is essential in the response to antigenic stimulation and in inducing the potent effector cells. B cell-DC, T cell-DC and DC-B cell-T cell interactions are regulated in predetermined sites by complex and varied mechanisms. Much recent evidence demonstrates that DCs modulate lymphocyte biology in its broadest aspects, including generation, differen-tiation, proliferation, and activation. In this review, we outline recent studies on the generation, structure, and function of lymphatic tissues, propose the concept of the "Lymphocyte-Dendritic Cell System (LDS)", and finally describe the significance and functions of this system in health and disease

Localization of blood coagulation factors in the germinal centers of human Peyer's patches

The immunohistochemical distribution of 15 blood coagulation factors in the germinal centers (GCs) of human Peyer's patches (PPs) was studied. Although factor VIII, active alpha-thrombin, and fibrinogen were hardly evident in the GCs, the majority of coagulation factors, such as kallikrein, high-molecular-weight kininogen, factos XII, X, IX, VII, V, XIIIa and XIIIb, prothrombin, anti-thrombin 111 and inactive alpha-thrombin were found, showing a lace-like staining pattern similar to that obtained with a monoclonal antibody, R4123, specific for follicular dendritic cells (FDCs) in the GCs. By immunoelectron microscopy, positive reactions for factor X and XIIIa were found on the surfaces of FDCs, GC cells, andlor in the intercellular spaces of GCs, being especially marked on the surface of the labyrinth-like structure of FDCs. It is concluded that a majority of coagulation factors are localized in the GCs of human PPs. Furthermore, it is suggested that some of these coagulation factors have a close topographical relationship with FDCs