A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo.
View Article and Find Full Text PDFObjective: The purpose of this study was to assess perfusion patterns seen on slow-infusion MR arteriography using the hepatic arterial infusion system compared with those seen on CT arteriography.
Subjects And Methods: In 37 patients with liver metastases who had implantable port systems for hepatic arterial infusion chemotherapy, slow-infusion MR arteriography using an infusion rate of 10 mL/hr through an implantable port and CT arteriography using an injection rate of 0.7 mL/sec were performed.
Tanpakushitsu Kakusan Koso
December 2002
Lnk is an adaptor protein expressed primarily in lymphocytes and hemopoietic precursor cells. Marked expansion of B lineage cells occurs in lnk(-/-) mice, indicating that Lnk regulates B cell production by negatively controlling pro-B cell expansion. In addition, lnk(-/-) hemopoietic precursors have an advantage in repopulating the hemopoietic system of irradiated host animals.
View Article and Find Full Text PDFA 48-year-old female presented with a subependymal giant cell astrocytoma (SEGA) without tuberous sclerosis manifesting as memory and mental disturbance. Magnetic resonance imaging showed a huge mass which was well-demarcated and extended from the anterior horn of the right lateral ventricle to the septal area on the right side. Surgery was performed with partial removal of the tumor.
View Article and Find Full Text PDFMany growth factors and hormones modulate the reproductive status in mammals. Among these, insulin and insulin-like growth factor I (IGF-I) regulate the development of gonadal tissues. SH2-B has been shown to interact with insulin and IGF-I receptors, although the role of SH2-B in these signals has not been clarified.
View Article and Find Full Text PDFPlastic deformation of materials occurs by the motion of defects known as dislocations and disclinations. High-resolution transmission electron microscopy was used to directly reveal the individual dislocations that constitute partial disclination dipoles in nanocrystalline, body-centered cubic iron that had undergone severe plastic deformation by mechanical milling. The mechanisms by which the formation and migration of such partial disclination dipoles during deformation allow crystalline solids to fragment and rotate at the nanometer level are described.
View Article and Find Full Text PDFWe present two cases of acute subclavian and/or axillary arterial occlusion after transaxillary catheterization with an implantable port for hepatic arterial infusion chemotherapy. They were successfully treated with thrombolytic therapy using intraarterial administration of urokinase without removal of the infusion catheter system. We consider that this treatment is suitable for managing acute thrombosis of the conduit artery after catheterization for hepatic arterial infusion chemotherapy.
View Article and Find Full Text PDFHematopoietic stem cells (HSCs) give rise to variety of hematopoietic cells via pluripotential progenitors and lineage-committed progenitors and are responsible for blood production throughout adult life. Amplification of HSCs or progenitors represents a potentially powerful approach to the treatment of various blood disorders and to applying gene therapy by bone marrow transplantation. Lnk is an adaptor protein regulating the production of B cells.
View Article and Find Full Text PDFThe interleukin-5 receptor alpha chain (IL-5Ralpha) is known to regulate the development and function of B cells and eosinophils. Although the functions of IL-5Ralpha cytoplasmic domain subregions have been studied extensively using cultured cell lines, this approach has limitations when studying the functions of distinct primary B-cell subpopulations and their responsiveness to IL-5. In the present study, we generated mice on an IL-5Ralpha null background, each expressing a mutant form of an IL-5Ralpha transgene ligated to a mu enhancer and VH promoter, either lacking the cytoplasmic DC3 region or substituting two proline residues for alanine (ApvA) in the membrane-proximal ppvp motif of the cytoplasmic domain.
View Article and Find Full Text PDFFormation of the pre-BCR complex is a critical check point during B cell development and induces the transition of pro-B to pre-B cells. CD79b (Igbeta) is a signaling component in the pre-BCR complex, since differentiation to the pre-B phenotype is induced by cross-linking the CD79b expressed on developmentally arrested pro-B cells from recombination-activating gene (RAG)-2-deficient mice. Bruton's tyrosine kinase (BTK) plays important roles in B cell development.
View Article and Find Full Text PDFThe lck gene encodes a protein-tyrosine kinase that plays a key role in signaling mediated through T cell receptor (TCR) and pre-TCR complexes. Transcription of the lck gene is regulated by two independent promoter elements: the proximal and distal promoters. Previous studies employing transgenic mice demonstrated that the sequence between -584 and -240 from the transcription start site in the mouse lck proximal promoter is required for its tissue-specific expression in the thymus.
View Article and Find Full Text PDFLnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens.
View Article and Find Full Text PDFWe present a case in which MR arteriography (MRA) with an indwelling catheter was used in a perfusion study of intrahepatic arterial chemotherapy for liver metastases. After embolization of collateral vessels using platinum coils, CT imaging was disturbed by strong artifact. However, platinum coils produced no MR artifact.
View Article and Find Full Text PDFBiochem Biophys Res Commun
May 2000
Engagement of cell-surface receptors leads to activation of protein tyrosine kinases, which in turn phosphorylate various downstream enzymes and adaptor proteins. Lnk is an adaptor protein that appears to be involved in signal transduction in lymphocytes, and forms an adaptor protein family with SH2-B. We tried to identify another member of the adaptor protein family and isolated the mouse APS (adaptor molecule containing PH and SH2 domains).
View Article and Find Full Text PDFThe right strategy for finding a new ESR dosimetric material sensitive to radiation is to follow the orthodox procedures used in the development of thermoluminescence dosimeters (TLD) and phosphorescence studies. Modern procedures used in materials sciences, such as computer calculation of molecular orbitals (MO), should be employed to estimate the ESR and optical properties of prospective materials. Radiation effects in lithium and magnesium sulfates and metal salts of organic acids, such as lithium and magnesium lactates, have been investigated in search for tissue-equivalent dosimeter with a large G value.
View Article and Find Full Text PDFBackground: TRAF6, a member of the tumour necrosis factor receptor-associated factor family, was first identified as a transducer of CD40 and interleukin-1 receptor (IL-1R) signals based on the interaction of TRAF6 with the cytoplasmic tail of CD40 and with the IL-1R associated kinase in vitro. However, the functions of TRAF6 in vivo remain unidentified.
Results: We show that TRAF6-/- mice exhibit severe osteopetrosis and are defective in osteoclast formation.
Acta Neurochir (Wien)
June 1999
The co-existence of multiple cerebral arteriovenous malformations (AVMs) and a spinal AVM is extremely rare. A 22-year-old man suddenly developed severe headache. Computed tomography (CT) scan showed intracerebral haemorrhage in the left occipital lobe.
View Article and Find Full Text PDFGan To Kagaku Ryoho
July 1998
Epirubicin and 5-FU were administered through an indwelling catheter inserted into the internal mammary artery and/or subclavian artery employing an implantable infusion port system for the treatment of unresectable advanced breast cancer and recurrent breast cancer. Intraarterial infusion chemotherapy proved to be an effective treatment modality for unresectable advanced breast cancer and recurrent breast cancer.
View Article and Find Full Text PDFStimulation of the T cell antigen receptor (TCR) activates a set of non-receptor protein tyrosine kinases that assist in delivering signals to the cell interior. Among the presumed substrates for these kinases, adaptor proteins, which juxtapose effector enzyme systems with the antigen receptor complex, figure prominently. Previous studies suggested that Lnk, a 38-kDa protein consisting of a single SH2 domain and a region containing potential tyrosine phosphorylation sites, might serve to join Grb2, phospholipase C-gamma1, and phosphatidylinositol 3-kinase to the TCR.
View Article and Find Full Text PDFStudies performed during the past several years make plain that ligand occupancy of antigen receptors need not necessarily provoke identical responses in all instances. For example, ligation of antigen receptors may stimulate a proliferative response, induce a state of unresponsiveness to subsequent stimulation (anergy), or induce apoptosis. How does a single type of transmembrane receptor induce these very heterogeneous cellular responses? In the following pages, we outline evidence supporting the view that the nature of the ligand/receptor interaction directs the physical recruitment of signaling pathways differentially inside the lymphocyte and hence defines the nature of the subsequent immune response.
View Article and Find Full Text PDFIn order to reduce toxic effects while attaining maximal therapeutic effects, epirubicin 10 mg/day, cyclophosphamide 100 mg/day and prednisolone 10 mg/day were administered through in indwelling catheter inserted into the internal mammary artery and/or subclavian artery for 3-4 weeks, employing the implantable port system for the treatment of unresectable breast cancer and recurrent cancer. Ten out of 11 patients (91%) with unresectable breast cancer showed a response (CR 3, PR 7, NC 1) to this modality of intra-arterial infusion chemotherapy. Seven out of 11 patients (64%) with recurrent cancer of the breast showed a response (CR 1, PR 6, NC 4).
View Article and Find Full Text PDFWe have examined phosphorylation mediated by cross-talk between growth signal pathways induced by IL-2 and IL-5. To analyze the phosphorylation process in the same cells, we established two sublines, T88-Mbeta1, which is a subline of a murine IL-5-dependent cell line, T88-M, by introduction of the human IL-2 receptor beta chain (IL-2Rbeta), and secondly CTLL-5Ralphabeta, which is a subline of a murine IL-2-dependent cell line, CTLL-2, by introduction of the murine IL-5 receptor alpha chain (IL-5Ralpha) and IL-5 receptor beta chain (IL-5Rbeta, betac) genes. Both T88-Mbeta1 and CTLL-5Ralphabeta expressed high-affinity receptors for IL-2 and IL-5, and proliferated in response to both factors.
View Article and Find Full Text PDFWe generated interleukin-5 receptor alpha chain (IL-5R alpha)-deficient (IL-5R alpha-/-) mice by gene targeting. The IL-5R alpha-/- mice showed decreased numbers of B-1 cells concomitant with low serum concentrations of IgM and IgG3. They showed no IL-5-induced enhancement of B cell responses to T-independent antigens.
View Article and Find Full Text PDFThe high-affinity receptor (R) for IL-5 consists of a unique alpha chain (IL-5R alpha) and a beta chain (beta c) that is shared with the receptors for IL-3 and granulocyte macrophage colony stimulating factor (GM-CSF). We defined two regions of IL-5R alpha for the IL-5-induced proliferative response, the expression of nuclear proto-oncogenes, and the tyrosine phosphorylation of cellular proteins including beta c, SH2/SH3-containing proteins and JAK2 kinase. In the studies described here, we demonstrate that IL-5, IL-3 or GM-CSF stimulation induces the tyrosine phosphorylation of JAK2, and to a lesser extent JAK1, and of STAT5.
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