In vitro negative selection of αβ T cell receptor transgenic thymocytes by conditionally immortalized thymic cortical epithelial cell lines and dendritic cells

We have established conditionally immortalized thymic cortical epithelial cell lines from transgenic mice carrying a temperature-sensitive SV40 large Tantigen. One of these cell lines expresses cortical markers and produces IL-1α, IL-6, IL-7, and TGF-β1. These cells express class I major histocompatibility complex (MHC) constitutively and class II MHC upon induction with IFN-μ. The cells appear to have a normal class I antigen presenting pathway since messages for both peptide transporter genes (TAP1, TAP2) were detected. The ability of these cortical epithelial cells to present peptide antigen was compared to that of thymic dendritic cells. In suspension culture with αβ Tcell receptor (TcR) transgenic thymocytes, these epithelial cells and dendritic cells (pre-pulsed with peptide cognate for the transgenic TcR) caused down-regulation of CD4, CD8, and TcR in an antigen dose-dependent and MHC-restricted manner. CD4^dullCD8^dull cells were taken as evidence for negative selection because these cells contained apoptotic DNA. Concentration of peptide required for negative selection of thymocytes was similar between dendritic cells and cortical epithelial cells. In contrast, αβ transgenic spleen cells were activated only by dendritic cells but not by cortical epithelial cells.     

Intravesical chemotherapy with 4′-epi-Adriamycin in patients with superficial bladder tumors

Summary We evaluated the effects of 4-epi-Adriamycin (EPI), a derivative of Adriamycin (ADR), in intravesical instillation chemotherapy. The patients received two courses of three daily instillations of 50–80 mg EPI dissolved in 30 ml physiological saline on 3 consecutive days, with an interval of 4 days between courses. Full evaluation was possible in 33 of 35 patients with superficial bladder tumors treated with EPI. Complete response was observed in 4 cases and partial response in 14 cases, giving a response rate of 55%. Side effects such as pollakiuria and pain on micturition occurred in 9 cases. EPI appears to be an effective agent for intravesical instillation chemotherapy in patients with superficial bladder tumors.     

HIV misconceptions among married women in Malawi: the role of household decision-making autonomy

Journal of Public Health - Married women face one of the highest HIV rates in Malawi. Although HIV misconceptions have been identified as a major contributor to HIV infection, we know very little...     

Arthus tonsillitis in the rabbit. Histological findings and fibrinolytic activity in the blood

Arthus-type hypersensitivity was induced experimentally in the tonsils of rabbits. Histopathological studies were performed on the Arthus tonsillitis so produced, and estimations of the plasma fibrinolytic activity were made on the blood of these rabbits. The findings obtained by macroscopic inspection of the tonsil revealed significant bleeding and swelling. Furthermore, the histopathological studies demonstrated bleed and infiltration of leukocytes into various parts of the parenchyma and connective tissue surrounding the tonsil during the early stages of tonsillitis. From the results concerning certain parameters of the fibrinolytic system in the blood, it was demonstrated that, during the early stage of tonsillitis, the fibrinolytic activity increased and whole plasmin was consumed. Based on the above findings, it seems that the change in fibrinolytic activity found in rabbits affected by Arthus tonsillitis closely resembles that in patients suffering from acute tonsillitis.     

IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells

Neurokinin 2 receptor (NK2R), a G protein‐coupled receptor for neurokinin A (NKA), a tachykinin family member, regulates various physiological functions including pain response, relaxation of smooth muscle, dilation of blood vessels, and vascular permeability. However, the precise role and regulation of NK2R expression in cancer cells have not been fully elucidated. In this study, we found that high NK2R gene expression was correlated with the poor survival of colorectal cancer patients, and Interferon (IFN‐α/β) stimulation significantly enhanced NK2R gene expression level of colon cancer cells in a Janus kinas 1/2 (JAK 1/2)‐dependent manner. NKA stimulation augmented viability/proliferation and phosphorylation of Extracellular‐signal‐regulated kinase 1/2 (ERK1/2) levels of IFN‐α/β‐treated colon cancer cells and NK2R blockade by using a selective antagonist reduced the proliferation in vitro. Administration of an NK2R antagonist alone or combined with polyinosinic‐polycytidylic acid, a synthetic analog of double‐stranded RNA, to CT26‐bearing mice significantly suppressed tumorigenesis. NK2R‐overexpressing CT26 cells showed enhanced tumorigenesis and metastatic colonization in both lung and liver after the inoculation into mice. These findings indicate that IFN‐α/β‐mediated NK2R expression is related to the malignancy of colon cancer cells, suggesting that NK2R blockade may be a promising strategy for colon cancers.