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T Kitamura

Publications and source records attributed to T Kitamura.

At least 37 records · Page 2Linked to original sources
PubMed1992

Common subunits of cytokine receptors and the functional redundancy of cytokines.

Several distinct cytokines often exhibit similar biological activities. The findings that high-affinity receptors for a group of cytokines with similar function share a common subunit with a critical role in signal transduction have provided a molecular basis for the functional redundancy of cytokines. Since the common subunit, together with distinct cytokine-specific receptor subunits, form high-affinity receptors, binding of one cytokine to its high-affinity receptor can be competed for by other cytokines in the same group.

Animals↗
PubMed1992

Effect of serum components on syncytium formation and virus production by cells infected with human immunodeficiency virus in vitro.

Previously it has been reported that cocultivation of human immunodeficiency virus type 1 (HIV-1)-infected cells with uninfected cells results in formation of multinuclear giant cells, generated via an interaction of gp120 on the surface of infected cells with CD4 on the uninfected cells. Formation of multinuclear giant cells as occurring in the presence of normal fetal calf serum was not observed when HIV-infected MOLT-4 or MOLT-3 cells (chronically infected with HTLV-IIIB) and uninfected cells were cocultured in both serum-free medium and fibrinogen-depleted serum. Addition of sera (human and rabbit) as well as of fibrinogen (human and bovine), fibronectin (human), and alpha-globulin (human), but not of albumin, transferrin or gamma-globulin to serum-free medium caused formation of multinuclear giant cells. In contrast, HIV production from MOLT-3 cells proceeds also in the absence of serum. In control experiments it was established that the cells maintained at reduced serum concentration, or in serum-free medium without or with fibrinogen are viable even though displaying a lower metabolic rate (ATP formation and DNA synthesis). From these findings we conclude that serum components (e.g., fibrinogen, fibronectin, and alpha-globulin) are absolutely required for syncytium formation but are not essential for virus release.

Adenosine Triphosphate↗
PubMed1992

Effects of low culture temperature on the induction of hsp70 mRNA and the accumulation of hsp70 and hsp105 in mouse FM3A cells.

We have shown that heat shock does not induce the synthesis of hsp70 in FM3A cells maintained at a low culture temperature of 33 degrees C although it does so in cells maintained at 37 degrees C [T. Hatayama et al. (1991) Biochem. Int. 24, 467-474]. In this paper, we show that FM3A cells maintained at 37 degrees C produced hsp70 mRNA during continuous heating at 42 degrees C or during postincubation at either 37 or 33 degrees C after being heated at 45 degrees C for 15 min, whereas cells maintained at 33 degrees C did not produce hsp70 mRNA during continuous heating at 37, 39, 42, or 45 degrees C, or during postincubation after being heated at any temperature. Thus the lack of hsp70 synthesis in cells maintained at 33 degrees C seemed to be due to the absence of hsp70 mRNA induction. Also, hsp70 was accumulated in cells maintained at 37 degrees C during continuous heating at 42 degrees C and during postincubation at 37 degrees C after heat shock at 45 degrees C, but not during postincubation at 33 degrees C. The cellular level of the constitutive hsp73 as well as the mRNA level were both similar in cells maintained at 33 and 37 degrees C. On the other hand, the cellular level of the constitutive hsp105 in cells maintained at 33 degrees C was only half of that in cells maintained at 37 degrees C. These hsp105 levels increased significantly in both types of cells after continuous heating at 39 degrees C. These findings indicate that the culture temperature affects not only the induction of hsp70 mRNA but also the accumulation of hsp70 and hsp105 in the cells.

Animals↗
PubMed1992

Cytokine receptors and signal transduction.

Cytokines play a vital role in coordinating immune and inflammatory responses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrinsic tyrosine kinase activity. Based on their structure, cytokine receptors are classified into several groups. High affinity receptors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distinct subunits, alpha and beta. The alpha subunits are primary cytokine binding proteins, and the beta subunits are required for formation of high affinity binding sites as well as for signal transduction. The GM-CSF, IL-3, and IL-5 receptors appear to share the same beta subunit in human, and therefore cross-talk among these cytokines may occur at the receptor level. High affinity receptors presumably are linked to various signal transduction pathways that lead to different cytokine functions. Differential expression of the cytokine receptors as well as reorganization of intracellular signalling pathways are critical for development of hemopoietic cells.

Amino Acid Sequence↗
PubMed1992

Production of phytochelatins in Polygonum cuspidatum on exposure to copper but not to zinc.

We studied cellular resistance to copper of plant cells Polygonum cuspidatum. When callus of P. cuspidatum was incubated on medium containing 100 microM cupric sulfate, the callus grew as well as the control callus did. The copper content of the callus, however, was elevated to a similar level of the medium. When cell extracts of callus exposed to 100 microM cupric sulfate were fractionated by gel filtration chromatography, a specific copper peak was eluted at the region of molecular weights between 4000 and 1000. Since an appearance of the copper-containing materials was inhibited by buthionine sulfoximine and the partially purified copper-containing materials contained only three amino acids: glutamic acid, glycine and cystine, the materials were supposed to be gamma-glutamyl peptides phytochelatins. Callus of P. cuspidatum synthesized phytochelatins from 50 microM cupric sulfate and maximally at 100-150 microM cupric sulfate. When induction of phytochelatins by another heavy metal, zinc, was analyzed, the callus, however, did not synthesize phytochelatins on exposure to zinc sulfate up to 1 mM. These findings suggested that phytochelatins were required for resistance to copper but probably not to zinc in the plant cells.

Cells, Cultured↗
PubMed1992

Stereotactic radiosurgery using a linear accelerator.

A basic and clinical study of radiosurgery using the linear accelerator (Linac) system for unremovable deep-seated brain tumors is reported. A Komai stereotactic ring was used to locate the target coordinates. The patient was laid on the Linac treatment table and held in the head fixation system. Irradiation was given in five positions. The dose profile by film dosimetry and Rando phantom was satisfactory. Seventeen tumors in 14 patients were treated. Clinical or histological diagnoses were nine metastases, one benign and two malignant gliomas, one meningioma, and one craniopharyngioma. Tumor sizes were between 8 and 30 mm. Doses were between 12 and 30 Gy. Computed tomographic evaluation after 3 months of 12 tumors in 11 survivors showed one complete remission, three partial remission, six no change, and two partial deterioration. For progressive tumors, Linac radiosurgery results are excellent.

Adult↗
PubMed1992

A structurally abnormal erythropoietin receptor gene in a human erythroleukemia cell line.

Restriction endonuclease mapping demonstrates a 3' end deletion of one erythropoietin receptor (EpoR) gene in TF-1 cells, a human erythroleukemia cell line that overexpresses the EpoR and proliferates in response to erythropoietin (Epo). EpoR mRNA transcripts are highly abundant and normal in size. These findings raise interesting questions about the possible role of this EpoR gene abnormality in the pathogenesis of the erythroleukemia from which this cell line was derived. This is the first report of an abnormal human erythropoietin receptor gene.

Blotting, Northern↗
PubMed1992

[A case of hepatocellular carcinoma responding to intraarterial infusion of epirubicin and mitomycin C].

A 64-year-old male was admitted for treatment of hepatocellular carcinoma. He was diagnosed as having many tumors in the area of S6 and the AFP level was elevated to 878 ng/ml. Initially, intraarterial infusion of Epirubicin only was not effective. After the first course of treatment, tumors increased in size and the AFP level was elevated. Next, intraarterial infusion of Epirubicin and Mitomycin C was performed. After the second course of treatment, the AFP level decreased from 5,006 ng/ml to 754 ng/ml and the tumors had almost completely disappeared on angiography. The tumors continued to decrease in size and thereafter the AFP level decreased to 10 ng/ml and was not elevated. The tumors almost completely disappeared in this case, and the coadministration of Epirubicin and Mitomycin C provided effective.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Production of interleukin 3 and granulocyte-macrophage colony-stimulating factor from stimulated blood mononuclear cells in patients with aplastic anemia.

Blood cells from patients with aplastic anemia (AA) were evaluated for the ability to produce interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on stimulation with phytohemagglutinin (PHA) or antilymphocyte globulin (ALG) by the use of an IL-3-dependent cell-line, TF-1, and the GM-CSF-IRMA kit. The IL-3 levels in patients with active AA were significantly lower, both in PHA-stimulated conditioned medium (CM) and in ALG-CM, than those of normal healthy donors (HD; p < 0.01). The degree of reduced IL-3 production in AA patients correlated well with the severity of neutropenia; the level of IL-3 returned to normal after successful treatment with ALG plus methylprednisolone (ALG therapy). On the other hand, GM-CSF production in AA patients varied widely and was only significant in remission patients in PHA-CM; in this case production was higher than that in active AA patients (p < 0.05) or in HD (p < 0.01). Sensitivity to PHA or ALG stimulation was evaluated by the ratio of IL-3 concentrations in ALG-CM versus PHA-CM (ALG/PHA index). The index varied widely from < 0.1 to > 10 in AA patients, contrasting to the clustered values in HD. Seven of the eight patients who had an ALG/PHA index of > 1.0 showed a good clinical response to ALG therapy. However, 12 of the 14 patients who had a lower index (< 1.0) failed to respond. The ALG/PHA index might have an ability to predict the response to ALG therapy.

Adolescent↗
PubMed1992

[Studies on the T-cell subset in lung tissue and BALF from patients with interstitial pneumonia].

The cellular components in bronchoalveolar lavage fluids (BALF) have been analyzed to obtain information on cellular kinetics in lung tissues of patients with diffuse pulmonary diseases. While various cells, alveolar macrophages, lymphocytes, and granulocytes appear in BALF, an increase in the percentage of lymphocytes has been noted in a variety of interstitial pneumonia. The T-cell subset of lymphocytes in BALF and biopsied lung tissues was, therefore, examined in patients with hypersensitivity pneumonitis (HP), sarcoidosis (Sar), idiopathic interstitial pneumonia (IIP) and rheumatoid arthritis with interstitial pneumonia (RA+IP) to compare the ratios of CD4/CD8 in BALF and lung tissues. The T-cell subset in BALF was analyzed by flow cytometry and the T-cell subset in lung tissues was detected with fresh frozen and thin-sliced specimens using an avidine-biotin complex (ABC) kit (Vecta Co. Ltd). The mean CD4/CD8 ratio in BALF was 0.36 in HP, 3.1 in Sar, 1.07 in IIP and 2.59 in RA+IP, while the mean CD4/CD8 ratio in lung tissues was 0.52 in HP, 2.59 in Sar, 1.11 in IIP and 2.25 in RA+IP, respectively. The ratios of CD4/CD8 in BALF and lung tissues from patients with these various interstitial pneumonia showed a positive correlation indicating that the changes of cellular components in BALF would reflect the changes in the lung tissues. Furthermore, CD4/CD8 ratios of lymphocytes infiltrating the alveolar portion and granuloma in lung tissues of HP were analyzed separately, because the CD4/CD8 ratios varied considerably from part to part of the lung tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolitis, Extrinsic Allergic↗
PubMed1991

Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors.

A cDNA for a human interleukin-3 (hIL-3) binding protein has been isolated by a novel expression cloning strategy: a cDNA library was coexpressed with the cDNA for the beta subunit of human granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor (hGMR beta) in COS7 cells and screened by binding of 125I-labeled IL-3. The cloned cDNA (DUK-1) encodes a mature protein of 70 kd, which belongs to the cytokine receptor family and which alone binds hIL-3 with extremely low affinity (Kd = 120 +/- 60 nM). A high affinity IL-3-binding site (Kd = 140 +/- 30 pM) was reconstituted by coexpressing the DUK-1 protein and hGMR beta, indicating that hIL-3R and hGMR share the beta subunit. Therefore, we designated DUK-1 as the alpha subunit of the hIL-3R. As in human hematopoietic cells, hIL-3 and hGM-CSF complete for binding in fibroblasts expressing the cDNAs for hIL-3R alpha, GMR alpha, and the common beta subunit, indicating that different alpha subunits compete for a common beta subunit.

Amino Acid Sequence↗
PubMed1991

Reconstitution of functional receptors for human granulocyte/macrophage colony-stimulating factor (GM-CSF): evidence that the protein encoded by the AIC2B cDNA is a subunit of the murine GM-CSF receptor.

The high-affinity receptor for human granulocyte/macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha subunit binds GM-CSF with low affinity, whereas the beta subunit does not bind GM-CSF by itself. The alpha and beta subunits together form the high-affinity GM-CSF receptor. The beta subunit has extensive sequence homology with the mouse interleukin 3 (IL-3) receptor (AIC2A) and its homologue (AIC2B) that does not bind IL-3 or other cytokines including GM-CSF. To examine the function of these receptor components, we expressed the alpha subunit of the hGM-CSF receptor with the human beta subunit or the mouse AIC2A or AIC2B in a mouse IL-3-dependent pro-B-cell line, Ba/F3, and in a mouse IL-2-dependent T-cell line, CTLL2. Coexpression of the alpha and beta subunits in Ba/F3 and CTLL2 cells resulted in high-affinity hGM-CSF binding and growth response to low concentrations of hGM-CSF. Whereas Ba/F3 cells expressing the alpha subunit alone proliferated in response to high concentrations of hGM-CSF, CTLL2 cells expressing the alpha subunit alone did not respond to hGM-CSF at all. Since Ba/F3 cells express endogenous AIC2A and AIC2B whereas CTLL2 expresses neither of them, we examined the possibility that either AIC2A or AIC2B is involved in the formation of a functional GM-CSF receptor. The expression of the human alpha subunit with AIC2B, but not with AIC2A, in CTLL2 cells conferred a growth response to hGM-CSF. These results indicate that the beta subunit of the GM-CSF receptor is required for generation of growth signals and that AIC2B is likely the beta subunit of the mouse GM-CSF receptor.

Animals↗
PubMed1991

Structural and functional analyses of glycosylation on the distinct molecules of human GM-CSF receptors.

We have previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) receptors are composed of at least two molecules of 80 and 135 kDa, which were denoted alpha- and beta-chains, respectively [Chiba, S., Shibuya, K., Piao, Y.-F., Tojo, A., Sasaki, N., Matsuki, S., Miyagawa, K., Miyazono, K. & Takaku, F. (1990) Cell Regul. 1, 327-335]. In this paper, we describe an investigation of the biochemical disparity noted between the alpha- and beta-chains of GM-CSF receptors using proteolytic and deglycosidic enzymes, and further demonstrate the potential importance of carbohydrate structures of the GM-CSF receptors using different lectins and glycoprotein synthesis inhibitors. Cross-linked alpha- and beta-chains with 125I-GM-CSF were digested by Staphylococcus aureus V8 protease and gave a different pattern. Furthermore, the size of the alpha-chain was reduced by 25 kDa by the removal of the N-linked oligosaccharides with peptidase: N-glycosidase F treatment, whereas that of the beta-chain remained unmodified by the enzyme. These results suggest that the alpha-chain of GM-CSF receptors agrees with the recently cloned low-affinity GM-CSF receptor [Gearing, D.P., King, J.A., Gough, N. M. & Nicola, N.A. (1989) EMBO J. 8, 3667-3676] having approximately 30% N-linked oligosaccharides and is biochemically different from the alpha beta-chain. By analyses using lectins, some of the oligosaccharides in the alpha-chain seem to be the complex-type and/or hybrid-type, because wheat germ agglutinin and leukoagglutinating phytohemagglutinin inhibited both GM-CSF-induced proliferation and GM-CSF binding to its receptors. Further analyses using glycoprotein synthesis inhibitors showed that N-linked processing of the alpha-chain, especially glucose removal by glucosidase I and II (whose activities are inhibited by deoxynojirimycin), appeared to be required for the expression onto the cell surface although the beta-chain expression was little affected by their inhibitors. Thus the beta-chain, probably located near the alpha-chain on the cell surface, was associated with a high-affinity class of GM-CSF receptors.

Cell Division↗
PubMed1991

Trajectory of spinocerebellar fibers passing through the inferior and superior cerebellar peduncles in the rat spinal cord: a study using horseradish peroxidase with pedunculotomy.

The course of spinocerebellar fibers in the rat spinal cord was investigated by injecting horseradish peroxidase into the cerebellar anterior vermis after complete transection of the left inferior and right superior cerebellar peduncles. By this procedure, fibers passing via the inferior cerebellar peduncles (icp-fibers) were labeled retrogradely on the right side of the spinal cord, whereas fibers passing via the superior cerebellar peduncles (scp-fibers) were labeled on the left side. Crossed icp-fibers were located diffusely in the anterior and lateral funiculi in the sacral to lower lumbar segments. They gradually migrated laterally and dorsally in these funiculi and received many uncrossed icp-fibers moving laterally in the lateral funiculus from the gray substance in the upper lumbar to lower thoracic segments. These mixed fibers shifted more dorsally and laterally in the anterior and lateral funiculi to aggregate in the narrow peripheral zone of the lateral funiculus in the upper thoracic and lower cervical segments, and received many crossed fibers in the upper cervical segments. There were more icp-fibers than scp-fibers through the spinal cord. However, the extent of scp-fibers in the anterior and lateral funiculi was essentially the same as that for icp-fibers, except that a few scp-fibers were found in the dorsolateral marginal zone of the lateral funiculus. It has been generally accepted that the dorsal spinocerebellar tract ascends in the dorsal half of the lateral funiculus and enters the cerebellum via the inferior cerebellar peduncle, whereas the ventral spinocerebellar tract ascends in the ventral half of it and takes the superior cerebellar peduncle route. The results of this study suggest that it is necessary to revise this concept.

Animals↗