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Biomedical subjects

M Hatakeyama

Publications and source records attributed to M Hatakeyama.

At least 91 records · Page 5Linked to original sources

[An experimental and clinical study of thin-slice high-resolution CT for lung detail].

The clinical usefulness of thin-slice high-resolution CT in the diagnosis of the chest was assessed by (1) experiments using a phantom and an inflated fixed lung (Heitzman's method), (2) evaluation of the CT delineativity of the bronchi and major fissure and (3) clinical examination of patients with diffuse pulmonary diseases. 1) In a phantom experiment using catheters, 10 mm-thick slice scan showed the 6 catheters as a single faint line. By 1.5 mm-thick slice scan, the catheters were defined as 6 separate lines. The profile images suggested that 1.5 mm-thick slice scan enables delineation of more minute details of structures. 2) In an experiment using an inflated fixed lung, 1.5 mm-thick slice scan produced more informative images that resembled macroscopic or soft X-ray images. 3) By 1.5 mm-thick slice scan, the subsegmental bronchi of both the right and left lobes were identified in most cases, while identification was possible in only half the cases by 10 mm-thick slice scan. 4) By 10 mm-thick slice scan, the sub-subsegmental bronchi were not identified in most cases. However, identification was possible in approximately half the cases by 1.5 mm-thick slice scan. 5) By 1.5 mm-thick slice scan, the major fissure was delineated as a linear shadow in most cases. It was hardly recognizable by 10 mm-thick slice scan. 6) In diffuse pulmonary diseases, 1.5 mm-thick slice scan allowed more minute visualization of the patho-morphological changes compared to 10 mm-thick slice scan. 7) Thin-slice high-resolution CT is thus expected to contribute to pathological analysis and more accurate diagnosis of pulmonary diseases.

Humans↗

Human interleukin 2 (IL 2) receptor beta chain allows transduction of IL 2-induced proliferation signal(s) in a murine cell line.

Interleukin 2 (IL 2) delivers cell growth signal by virtue of its interaction with the high-affinity receptor complex, which consists of two distinct IL 2-binding molecules: the IL 2 receptor alpha (IL 2R alpha) and beta (IL 2R beta) chains. Unlike many known growth factor receptors, neither of the IL 2R chains seems to contain a tyrosine kinase domain. In this report, we have shown that the human IL 2R beta chain expressed in a murine IL 3-dependent, non-lymphoid cell line can transduce IL 2-induced cell proliferation signal(s) in combination with the autologous mouse IL 2R alpha chain. This observation should provide a tool to dissect IL 2-induced signal transduction pathway in lymphoid and non-lymphoid cells.

Animals↗

Transient induction of IL-2 receptor in cultured T cell lines by HTLV-1 LTR-linked tax-1 gene.

Human lymphotropic virus, HTLV-1, encodes in its proviral genome a transcriptional activator protein, tax-1, that may be responsible for the development of virus-induced adult T cell leukemia (ATL), possibly through the aberrant activation of the genes for interleukin-2 (IL-2) and one of its receptor (IL-2R) components, the IL-2 receptor alpha-chain (IL-2R alpha). In the present study, an expression plasmid containing tax-1 cDNA under the control of HTLV-1 LTR was introduced into mouse and human CD4-positive T cell lines. Analysis of the established cell clones revealed a number of interesting features: (i) a limited fraction of the total cell population (less than 25% in each clone) was positive for IL-2R alpha; (ii) the IL-2R alpha expression was not permanent, as the IL-2R alpha positive and negative cells could convert either way. The experimental data suggest that the observed heterogeneity in IL-2R alpha expression in the transformants is due to a cell-cycle-regulated expression and function of tax-1. Furthermore, a proportion of the induced IL-2R in EL-4 was in high-affinity form, suggesting the association of the IL-2R alpha and the IL-2R beta chain (p70-75) components.

Animals↗

Structure of the functional interleukin-2 receptor. Evidence for the association of human p55 and murine p75 molecules in a mouse T cell line.

The structural basis of the high affinity interleukin-2 receptor which was previously reconstituted in a cultured murine T cell line, EL4 by expressing either wild-type Tac antigen complementary DNA (cDNA) or a chimeric cDNA was characterized. The chimeric cDNA encodes a membrane portion whose extracellular portion consists of that of Tac antigen whereas transmembrane and cytoplasmic portions consists of those the human insulin beta chain. The Tac antigen/anti-Tac antibody complex was treated by chemical crosslinking reagents, purified by goat anti-mouse immunoglobulin (Ig), and was analysed by SDS-PAGE. We here demonstrated the presence in mouse EL4 transfectants of a novel membrane protein which is closely associated with the products of transfected cDNAs in the absence of interleukin-2. The protein is 75 kDa in size and is detected in cells which express high affinity interleukin-2 receptor but not in cells which only express low affinity interleukin-2 receptor. The transmembrane region and the cytoplasmic region of Tac antigen is not necessary for the formation of the complex consisting of Tac antigen and 75 kDa molecule, indicating that a murine 75 kDa molecule associates with Tac antigen extra-cellularly.

Animals↗

Right upper lobe versus right middle lobe: differentiation with thin-section, high-resolution CT.

A new method was developed to differentiate the upper lobe from the middle lobe of the right lung with thin-section, high-resolution computed tomography. In the upper lobe, a medial subsegmental bronchus of an anterior segmental bronchus is always located lateral to the corresponding artery. In the middle lobe, a medial subsegmental bronchus of a lateral segmental bronchus and a superior and inferior subsegmental bronchus of a medial segmental bronchus are always located medial to the corresponding artery. In other words, the anatomic relationship between the subsegmental bronchi and the corresponding pulmonary arteries in the upper lobe is opposite to that in the middle lobe. One hundred seventeen cases, including 54 cases of lobar volume loss, were reviewed with this method, and in each case it was possible to differentiate the upper lobe from the middle lobe without the contiguous section analysis.

Adult↗

Proliferative responsiveness of B cells from autoimmune NZB mice to anti-immunoglobulin and interleukin-4.

Proliferative responses of B cells to anti-IgM antibody and recombinant interleukin-4 (rIL-4) were studied in autoimmune NZB mice. While anti-IgM antibody and rIL-4 act synergistically on resting B cells to induce proliferation in BALB/c and C57BL/6 mice, they failed to produce synergistic effect on NZB B cells, although these NZB B cells responded better to the individual stimulus with anti-IgM antibody or rIL-4. Cell-fractionation analysis of NZB splenic B cells using Percoll density centrifugation showed marked increase in low-density B cells and decrease in high-density B cells. Proliferative response patterns of each subpopulation of NZB B cells were not different from those of control BALB/c B cells, except for higher response of NZB B cells to anti-IgM antibody. Thus, the accumulation of large low density B cells, probably resulting from in vivo activation, may partly account for the altered responsiveness of NZB B cells as a whole.

Animals↗

Overcoming suppression of antitumor immune reactivity in tumor-bearing rats by treatment with bleomycin.

We investigated the immunological role of bleomycin (BLM) in the treatment of KMT-17 fibrosarcoma-bearing rats. We were able to detect antitumor immune reactivity by using a mixed-lymphocyte tumor culture in spleen cells shortly after the transplantation of a KMT-17 fibrosarcoma in syngeneic Wistar King Aptekman/HMK rats. The reactivity declined following the progression of the tumor and was completely inhibited 11 days after the tumor transplantation. After the 11th day, however, spleen cells from BLM-treated KMT-17-bearing rats demonstrated higher antitumor immune reactivity. This result corresponds to those we obtained from an in vivo tumor-neutralizing assay (Winn assay). Macrophages from untreated tumor bearers were unable to inhibit the immune reactivity against KMT-17 cells in the mixed-lymphocyte tumor culture. Neither the tumor-bearing state nor the BLM treatment seemed to have any significant influence on another macrophage function, the antigen-presenting cell activity. However, a T-enriched fraction from untreated KMT-17 bearers showed a definite suppression activity on the generation of cytotoxic T-lymphocyte activity against KMT-17 tumor in the mixed-lymphocyte tumor culture; in contrast, no T-suppressor activity could be detected in the same fraction taken from BLM-treated tumor bearers. Our investigation suggests that BLM eliminates the tumor-specific T-suppressor activity without having any influence on responder T-lymphocytes in the cell-mediated antitumor immune reactivity.

Animals↗

The expression of the p75 subunit of interleukin 2 receptor in Tac negative leukemic cells of two patients with large granular lymphocytic leukemia.

The expression of interleukin 2 receptor (IL-2R) on leukemic cells of natural killer (NK) and T cell lineages in two patients with large granular lymphocytic (LGL) leukemia was examined. The p55 Tac IL-2R was not detected by the indirect immunofluorescence method and it did not participate in the IL-2 binding to the surface of these cells. However, these leukemic cells proliferated in a IL-2 dose-dependent manner and expressed p55. A p75 IL-2 receptor (IL-2-R) subunit was detected on the LGL leukemic cells of both NK and T lineages in a crosslink assay. Thus, it is suggested that the primary signal of IL-2 is mediated by the p75 alone. A study of the inhibitions of the proliferative response of LGL leukemia cells by anti-Tac revealed that both p75 and secondarily induced p55 are required for the cell proliferation.

Aged↗

Regulation of cytokine gene expression: gene activation in type I IFN and IL-2 systems.

Cytokines represent essential soluble mediators in cell-to-cell communication and they are known to play crucial roles in many biological processes, including viral infection, inflammation and immunity. We have been focusing on two cytokine systems, the interferon (IFN) and interleukin 2 (IL-2) systems each of which respectively plays a key role in viral infections and the immune response. In both cases, expression of those cytokines and, in the case of IL-2 system, the receptor is tightly regulated at the transcriptional level. Recent studies in our laboratory as well as others have uncovered the mechanism(s) operating in the regulation of those genes and have provided further insights on how the two cytokine systems operate and what is the biological significance of gene regulation in these systems. Here, we summarize the current understanding of the IFN system and IL-2 system in the context of host defense against viral infections and T cell neoplasms, respectively.

Amino Acid Sequence↗

Transmembrane signaling of interleukin 2 receptor. Conformation and function of human interleukin 2 receptor (p55)/insulin receptor chimeric molecules.

Chimeric genes were constructed which gave rise to the expression of novel receptor molecules consisting of the extracellular domain of the human interleukin 2 receptor (IL-2-R; p55 or Tac antigen) joined to the transmembrane domain and either full-length or truncated cytoplasmic domain of the human insulin receptor (Ins-R). Expression studies using mouse T cell line EL-4 revealed that the chimeric receptors are able to manifest properties indistinguishable from the authentic IL-2-R. On the other hand, stimulation of the tyrosine kinase activity by IL-2 was not observed in the chimeric receptor with the entire cytoplasmic domain of the Ins-R. These findings thus shed light on the structural conformation and functioning of the IL-2-R complex.

Animals↗

Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering.

In this study we provide evidence that distinct DNA sequences within the 5'-flanking regions of the genes for interleukin-2 (IL-2) and its receptor (IL-2R) are involved in human T-cell-specific activation of transcription by p40x, a product of human T cell leukemia virus type I (HTLV-1). The same DNA sequences appear to be responsible for induction of the genes in a T cell line, Jurkat, by mitogens. Although the IL-2 gene sequences are activated by p40x with much lower efficiency than the IL-2R gene sequences, they are synergistically activated by the p40x expression and subsequent extracellular stimulation by Concanavalin-A or anti-T3. We propose a model for two-step activation of the IL-2 autocrine loop in ATL development.

Cell Line↗

Functional interleukin 2 receptors on B cells lacking Tac antigens.

Human B lymphoblastoid line, SKW 6-4, cells were induced to IgM-secreting cells by high concentrations of interleukin 2 (IL 2). These cells were found to be unreactive with anti-Tac antibody and did not express mRNA detectable for Tac antigen. In Scatchard plot analysis, low-affinity IL 2-binding sites were found on SKW 6-4 cells. Moreover, analysis of the IL 2-binding molecules revealed ones (molecular weight 70,000 and 75,000) distinct from Tac antigen. It is conceivable that IL 2 exerts its effect through its interaction with these novel IL 2-binding molecules in SKW 6-4 cells.

Antigens, Surface↗