Evidence for a Stable Intermediate in Leukemia Virus Activation in AKR Mouse Embryo Cells

Analysis of the requirement for serum in the activation of the endogenous leukemia virus expression in AKR mouse embryo cells by 5-iododeoxyuridine shows that activation can be dissociated into two discrete serum-dependent events. The first involves incorporation of 5-iododeoxyuridine into DNA and results in the formation of a stable “activation intermediate” resembling the provirus formed during infection of stationary mouse embryo cells with exogenous leukemia virus. The second event, resulting in expression of the activation intermediate as synthesis of virus proteins, requires DNA replication but not 5-iododeoxyuridine.     

Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism

Normal mast cells can be propagated in culture when medium is supplemented with interleukin-3 (IL-3). We demonstrate that Abelson-MuLV (Ab-MuLV) infection of mast cells eliminates dependence on IL-3 for growth. By contrast, Harvey, BALB, and Moloney MSV, which also productively infect mast cells, are unable to relieve IL-3 dependence. Ab-MuLV-induced IL-3-independent lines express the v-abl-specific transforming protein and have phenotypic characteristics of mast cells. These cells also possess high cloning efficiencies in soft agarose and are tumorigenic in nude mice. In addition, Ab-MuLV induces transplantable mastocytomas in pristane-primed adult mice resistant to lymphoid transformation, defining a new hematopoietic target for malignant transformation by this virus. None of the Ab-MuLV-derived transformants express or secrete detectable levels of IL-3 nor is their growth inhibited by anti-IL-3 serum. These results argue that Ab-MuLV abrogation of the IL-3 requirement is not due to an autocrine mechanism.     

Infection of immune mast cells by Harvey sarcoma virus: immortalization without loss of requirement for interleukin-3.

Cells from adult mouse spleens were cultured in WEHI-3 cell-conditioned medium, which contains the lymphokine interleukin-3 (IL-3). Under these conditions, cells grow well for 4 to 8 weeks; the cultures contain a variety of cell types for the first 1 to 2 weeks but are subsequently composed largely of immune mast cells. We found that infection of these cultures with Harvey sarcoma virus (HaSV) profoundly enhanced the growth potential of the cells, resulting in the reproducible isolation of long-term cell lines. These HaSV-infected cells appeared to be phenotypically identical to the immune mast cells found in uninfected cultures as determined by biochemical, immunological, and cytological tests. Although the cells expressed protein p21Ha-ras at levels similar to those in HaSV-transformed fibroblasts, they continued to require IL-3 for growth in vitro. Similar IL-3-dependent, long-term mast cell lines were also cultured from the enlarged spleens present in HaSV-infected mice. These results suggest that high-level expression of an activated Ha-ras oncogene enhances growth in these cells, perhaps by stimulating the progression of the cells into S, without affecting differentiation or altering the requirements for normal growth factor.     

Early onset pre-eclampsia: recognition of underlying renal disease.

A follow up study of 84 patients with early onset pre-eclampsia (before 37 weeks'' gestation) showed a high prevalence of underlying renal disease. Renal abnormalities were found in 33 of the 49 primiparas (67%) and in 22 of the 35 multiparas (63%). Two thirds of the multiparas with pre-eclampsia before 37 weeks with a diagnosis of either essential hypertension or renal disease had recurrent pre-eclampsia. Maternal morbidity and fetal mortality were greater in the group with early onset pre-eclampsia than in a group with late onset disease. Idiopathic pre-eclampsia occurred in 10% of primiparas in the early onset group, whereas it was the main condition in over three quarters of primiparas in the late onset group. A presumptive diagnosis of idiopathic pre-eclampsia is likely to be correct only in primiparas who develop the disease after 37 weeks of pregnancy; in all other cases careful search will almost certainly detect an underlying abnormality, predominantly renal.     

Identification of CD13, CD107a, and CD164 as novel basophil-activation markers and dissection of two response patterns in time kinetics of IgE-dependent upregulation

INTRODUCTIONBasophils and mast cells are important effector cells ofinflammatory reactions [1-3]. In contrast to eosinophilsand neutrophils, they possess high-affinity immunoglo-bulin (Ig) E receptors (FcεRI) that are cross-linked uponengagement of recep…     

CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells

CCL18 is a human chemokine secreted by monocytes and dendritic cells. The receptor for CCL18 is not yet known and the functions of this chemokine on immune cells are not fully elucidated. In this study, we describe that CCL18 is present in skin biopsies of atopic dermatitis (AD) patients but not in normal or psoriatic skin. CCL18 was specifically expressed by APCs in the dermis and by Langerhans and inflammatory dendritic epidermal cells in the epidermis. In addition, the serum levels of CCL18 and the percentages of CCL18-producing monocyte/macrophages and dendritic cells were significantly increased in AD patients compared with healthy controls. Furthermore, we demonstrate that CCL18 binds to CLA(+) T cells in peripheral blood of AD patients and healthy individuals and induces migration of AD-derived memory T cells in vitro and in human skin-transplanted SCID mice. These findings highlight a unique role of CCL18 in AD and reveal a novel function of this chemokine mediating skin homing of a subpopulation of human memory T cells.     

Degradation and release from the thylakoid membrane of Photosystem II subunits after UV-B irradation of the liverwort Conocephalum conicum

The effect of ultraviolet-B (UV-B) radiation on the amount of various Photosystem (PS) II subunits has been studied in the thalloid liverwort Conocephalum conicum. UV-B irradiation led to a drastic decrease of the reaction center proteins D1 and D2 and the outer light harvesting antenna (LHC II). A minor reduction was found in the levels of the CP 43 polypeptide of the inner antenna and the 33, 23 and 16 kDa extrinsic polypeptides of PS II. During UV-B irradiation, the extrinsic polypeptides accumulated in the soluble protein fraction, but D1 and D2 were not dedectable. Streptomycin, but not cycloheximide inhibited the repair process of PS II, indicating that only protein synthesis in the chloroplast is necessary for recovery. This indicates that the extrinsic proteins of PS II dissociate from the membrane during UV-B treatment and reassociate with PS II in the course of the repair process. We conclude that the reaction center core is a target of UV-B radiation in C. concicum. The extrinsic proteins of PS II are not directly affected by UV-B, but their release is the consequence of UV-B-induced degradation of the D1 and D2 proteins.     

Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.

Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.     

Genetic mapping of the mouse interleukin 3 gene to chromosome 11

Interleukin 3 (IL 3) is a T cell-derived lymphokine that induces the proliferation and differentiation of early hematopoietic stem cells. By using a cDNA clone for IL 3, a single Eco-RI restriction fragment of 8.5 kbp was detected in Southern blot hybridizations of DNA from BALB/c and C57BL/10 mice, whereas an Eco-RI restriction fragment of 10.8 kbp was detected in NFS and A/J mice. Under the conditions used, no hybridization was detected to Chinese hamster DNA. The species and strain differences were used to analyze a series of hamster X mouse somatic cell hybrids and genetic crosses between NFS and C57BL/10 mice. The results demonstrate that the IL 3 gene is located on chromosome 11.