Enhanced transcription of TNF in systemic vasculitis.
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Gene Amplification↗
Biomedical subjects
S Kishimoto
Publications and source records attributed to S Kishimoto.
Structure of the gene encoding the muscle-specific subunit of human phosphoglycerate mutase.
We report the isolation and analysis of genomic clones containing the entire gene encoding the muscle-specific subunit of human phosphoglycerate mutase. The gene spans 2.83 kilobase pairs and has a three-exon/two-intron structure that is similar to the organization of the human 2,3-bisphosphoglycerate mutase gene (Joulin, V., Garel, M.-C., LeBoulch, P., Valentin, C., Rosa, R., Rosa, J., and Cohen-Solal, M. (1988) J. Biol. Chem. 263, 15785-15790), in that the second introns of both genes are localized precisely at the same position. A canonical TATA box and an inverted CCAAT box are present immediately upstream of this gene. Comparison with other muscle-specific enzyme genes reveals a conserved 9-base pair element (GGGGCTGGG) in the 5'-flanking region that may be associated with the expression of genes encoding muscle-specific enzymes.
Amino Acid Sequence↗
Partial purification and characterization of human hepatoma-derived growth factor.
A human hepatoma cell line, HuH-7, which was established from a hepatoma tissue removed at surgical operation from an adult Japanese male, grows autonomously in a serum-free chemically defined medium. A human hepatoma-derived growth factor with potent growth-promoting activity, was partially purified from the conditioned medium of HuH-7 cells, using ion-exchange, heparin affinity chromatography and gel filtration. The partially purified growth factor (HuHGF) is acid- and heat-labile, and sensitive to reduction and trypsin digestion. HuHGF, which is of relatively high molecular weight (about 64 kDa) examined by gel filtration, stimulates not only the DNA synthesis of Swiss mouse 3T3 fibroblasts, but also the growth of HuH-7 cells in serum-free chemically defined medium, suggesting that it is produced by and acts on HuH-7 cells as an autocrine growth factor. This putative growth factor may play an important role in the autonomous growth of hepatoma and may lead to useful diagnostic or therapeutic approaches to human hepatoma.
Carcinoma, Hepatocellular↗
A novel VHDJH to JH joining that induces H chain production in an Ig-null immature B cell line.
A novel Ig H chain gene rearrangement, a VHDJH to JH joining, was observed in an Ig-null immature B cell line. The preexisting, nonproductive VHDJH complex was replaced by the productive VHJH complex which was generated by the novel joining between the rearranged VH and a germ line JH gene. This VHDJH to JH joining is thought to be a site-specific recombinational event mediated by a putative recombination signal sequence, CACAGCC-12-base-GCAAGAAAG, embedded in the rearranged VH gene including the N region. This sequence might be a novel recombination signal sequence, which had not yet been reported, for so-called recombinase.
Amino Acid Sequence↗
Enhanced tumor growth and metastatic spread of an MH134 variant lacking a part of the MM antigen: a possible role of antibody-dependent cellular cytotoxicity in control of tumor growth and metastases.
The role of antibody-dependent cellular cytotoxicity (ADCC) in host defense against tumor growth and metastasis was investigated with MH134, an MM antigen-positive murine hepatoma, and MH134-M, a variant with enhanced tumorigenesis and metastasis, in syngeneic C3H/HeN mice. When inoculated subcutaneously into C3H/HeN mice, MH134-M tumors grew more rapidly than did MH134 tumors and consistently metastasized to the draining lymph nodes, whereas MH134 tumors did not. Also, MH134-M exhibited a significantly greater lung colonization potential than did MH134, when inoculated intravenously into C3H/HeN mice. In BALB/c nu/nu mice, however, solid MH134 tumors grew and metastasized to the same extent as MH134-M, indicating that there is no significant intrinsic difference between these two tumor lines in proliferative or metastatic capacity. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting, performed after SDS-PAGE analysis of cellular extracts with a monoclonal antibody (MAb) that recognizes a part of the MM-antigen, revealed that the cells of MH134-M lack at least a part of the MM antigen. Sera of C3H/HeN mice bearing solid MH134 tumors were found to contain anti-MM-antigen antibodies, when tested by immunoblotting of SDS-PAGE-developed materials. Cytotoxicity testing in which thioglycollate-induced peritoneal macrophages were used as effector cells revealed that antibodies present in sera strongly induced ADCC to MH134 but not to MH134-M. On the other hand, sera of MH134-M tumor-bearing C3H/HeN mice neither contained anti-MM-antigen antibodies nor induced ADCC to MH134 or MH134-M tumor cells. Intravenous injection of carrageenan into C3H/HeN mice bearing solid MH134 tumors significantly enhanced tumor growth, whereas the growth of subcutaneously injected MH134-M tumors was not influenced by this treatment. These results suggest that the enhanced tumorigenesis and metastasis of the MH134-M line in C3H/HeN mice are based, at least in part, on significant loss of the MM antigen and the resultant inability to induce ADCC-triggering antibody production during tumor growth.
Animals↗
The DJH complex remains active in recombination to VH segments after the loss of mu-chain expression in mu-positive pre-B cells.
AT11-2 is an Abelson virus-transformed B precursor cell line which is capable of differentiating Ig- from mu+ cells via functional recombination of VH segments to preexisting DJH complexes. We describe here that after a mu+ subclone (VDJ+/DJ) generated from Ig- AT11-2 (DJ/DJ) cells by in vitro functional VH to DJH recombination subsequently lost mu-chain expression either by the recombination of a pseudo VH segment to the VHDJH+ allele or by the deletion of VHDJH+ allele, a novel productive joining of VH segments to the preexisting DJH complex occurred. These results indicated that VH to VHDJH rearrangement was not suppressed in mu-chain producing cells and that the DJH complexes still remained active in the recombination to VH segments after the loss of mu-chain expression. Our results may also suggest that VH to DJH rearrangement, but not VH to VHDJH rearrangement, is suppressed in mu-chain producing cells to maintain allelic exclusion. Our cell differentiation system should continue to be valuable for elucidating the mechanism of suppression and associated implications regarding allelic exclusion.
Amino Acid Sequence↗
Effect of androgen on proliferation of estrogen-responsive transformed mouse Leydig cells in serum-free culture.
We examined the effects of steroid hormones on the proliferation of transformed mouse Leydig cells (B-1) in serum-free culture condition. Among hormones examined, androgen as well as estrogen enhanced the cell proliferation rate. Hormone binding studies revealed that B-1 cells contained both androgen and estrogen receptors. In addition, androgen-enhanced cell growth was inhibited by antiandrogen, but not by antiestrogen, while estrogen-stimulated cell growth was suppressed by antiestrogen. However, the simultaneous addition of androgen and estrogen did not show an additive effect. Dose-response study on androgen-dependent cell growth revealed that relatively high concentrations (10(-7)-10(-6) M) of dihydrotestosterone were required to obtain the maximum response. This was at least partly explained by the finding that B-1 cells could metabolize dihydrotestosterone into the less active steroids. Finally, B-1 cells were found to grow more rapidly in normal than in castrated male mice. These results clearly indicate that the proliferation of B-1 cells is stimulated by both androgen and estrogen, which utilize the different receptor systems.
Androgens↗
Mutant fibronectin gene in skin fibroblasts of sclerotic lesions from patients with progressive systemic sclerosis.
A mutant fibronectin gene was identified in skin fibroblasts obtained from sclerotic lesions of 7 patients with progressive systemic sclerosis. We found 2 point mutations adjacent to the cell-attachment tetrapeptide DNA sequence in the cell-binding domain of the fibronectin gene. This observation suggests that the mutant fibronectin is related to an integral component of sclerotic pathogenesis through abnormal cellular interactions.
Amino Acid Sequence↗
Decreased expression of interleukin-2 binding molecules (p70/75) in T cells from patients with systemic lupus erythematosus.
Using radiolabeled interleukin-2 (IL-2), affinity cross-linking and binding assays revealed that the expression of intermediate-affinity IL-2 binding molecules (p70/75) on freshly prepared T cells from patients with systemic lupus erythematosus (SLE) was significantly decreased in comparison with that in normal subjects. The proliferative response of T cells to high doses of IL-2 was also reduced in patients with SLE. The decreased expression of p70/75 reflects the hyporesponsiveness to IL-2 of T cells in patients with SLE.
Adult↗
Induction of tumoricidal macrophages from bone marrow cells of normal mice or mice bearing a colony-stimulating-factor-producing tumor.
Nonadherent cells of the bone marrow of C3H/HeN mice were incubated for 3 days with the culture supernatant of an L-929 cell line containing macrophage-colony-stimulating factor. Approximately, 70% of the cells became phagocytic, adherent to plastic dishes and positive for nonspecific esterase staining. The adherent cells exhibited a weak tumoricidal activity against syngeneic mammary carcinoma cells, and the cytotoxicity was strongly augmented by the addition of bacterial lipopolysaccharide to the cytotoxicity assay. The cytotoxicity induced by lipopolysaccharide was also shown to be mediated by Thy1.2- and asialo-GM1+ cells, and was abrogated by the addition of carrageenan. Macrophage-colony-stimulating-factor-producing (D66) and nonproducing (A23) variants were separated from the MM48 tumor line in in vitro culture following limiting dilution. There was no difference between these two variants in either the in vitro growth rate or the susceptibility to macrophage-mediated cytotoxicity. C3H/HeN mice inoculated i.p. with D66 survived longer than did those inoculated i.p. with A23. C3H/HeN mice bearing D66 or A23 as an ascitic form were given i.p. injections of Nocardia rubra cell wall skeleton (N-CWS). N-CWS significantly prolonged the survival period of mice bearing D66, whereas it exhibited no apparent antitumor effect on mice bearing A23. The increase in the cell number of D66 in the peritoneal cavity was significantly retarded, compared with that of A23. In contrast, the number of peritoneal macrophages increased more in D66-bearing mice than in A23-bearing mice. The increase in the peritoneal macrophage number was further augmented by an i.p. injection of N-CWS. Peritoneal macrophages of D66-bearing mice exhibited apparent tumoricidal activity against MM48 tumor cells in the presence of lipopolysaccharide, and the cytotoxicity was significantly augmented by i.p. injection of N-CWS. On the other hand, the responsiveness of peritoneal macrophages to lipopolysaccharide was found to be poor in A23-bearing mice and the tumoricidal activity was only weakly augmented by N-CWS. These results strongly suggest that M-CSF plays an important role not only in the maturation of macrophage progenitors but also in the induction and the accumulation of activated macrophages.
Animals↗
Administration of recombinant IL-2 augments the level of serum IgM in an IL-2 deficient patient.
A patient with ataxia telangiectasia was treated with recombinant interleukin-2 (rIL-2) and the resulting immunological effects evaluated. The patient lacked IL-2 production, and immunoglobulin synthesis was also impaired. Treatment with IL-2 selectively increased serum IgM without any significant side effects. Therapy also restored B-cell function in vitro. IgM production as well as the proliferative response to Staphylococcus aureus strain Cowan I. These results suggest that IL-2 treatment may correct both T-cell and B-cell defects.
Adolescent↗
Augmentative effect of Nocardia rubra cell-wall skeleton on the induction of human lymphokine-activated killer (LAK) cells by the production of LAK cell helper factor(s).
Nocardia rubra cell wall skeleton (N-CWS) was found to synergistically augment lymphokine-activated killer (LAK) cell generation from human peripheral blood mononuclear cells (PBMC) in the presence of a suboptimal dose of recombinant interleukin-2 (rIL-2). N-CWS increased the number of PBMC expressing IL-2 receptor on their surfaces, and the presence of N-CWS at the early stage of the culture period was essential for the exertion of its augmentative activity on the LAK induction. The predominant phenotype of LAK precursor cells responding to N-CWS and rIL-2 was CD3- CD16+. Culture supernatant from N-CWS-stimulated PBMC was found to act as a substitute for N-CWS in the induction of LAK generation in the presence of rIL-2, suggesting that these cells produced a factor capable of augmenting LAK cell induction (LAK helper factor, LHF). LHF was found to have a molecular mass of 29 kDa by gel filtration, and could also function as a killer helper factor to augment allo-antigen-specific cytotoxic T lymphocyte generation from human peripheral blood T cells as well as murine thymocytes. LHF showed no species specificity, indicating that it is different from IL-4. The enhancing activity of LHF was not neutralized with anti-TNF alpha, anti-IL-1 alpha, or anti-IL-1 beta antibodies. Furthermore, no tumor necrosis factor-alpha (TNF alpha), TNF beta, IL-1 alpha, beta, IL-2, IL-5, IL-6 or interferon activity was detected in semi-purified LHF during enzyme-linked immunosorbant assay and biological assays. The present findings indicate that LHF produced from N-CWS-stimulated PBMC is a molecule distinct from TNF alpha, TNF beta, interferon, IL-1, -2, -4, -5, and -6, and suggest that LHF might be a novel lymphokine involved in LAK generation.
Adjuvants, Immunologic↗
Elevation of serum interleukin 6 prior to acute phase proteins on the inflammation by surgical operation.
Serum levels of interleukin 6 (IL-6) and acute phase proteins were measured in patients who underwent surgical operation. Elevation of IL-6 preceded that of acute phase proteins, indicating that the measurement of serum IL-6 may be helpful for the early detection of an inflammatory state.
Acute-Phase Proteins↗
Immunopharmacological actions of an extract isolated from inflamed skin of rabbits inoculated with Vaccinia virus (Neurotropin)--II. Restorative effect on immune responses through the recovery of IL-2 production in aging mice.
To examine the immunopharmacological actions of an extract isolated from inflamed skin of rabbits inoculated with Vaccinia virus (Neurotropin), its effect on the immune responses in aging BALB/c mice was examined. Neurotropin clearly restored the decreasing T-cell-dependent immune responses such as delayed-type hypersensitivity (DTH) response and plaque-forming cells (PFC) response to sheep red blood cells (SRBC) when administered i.p. from 13 months old (mo) to 16 mo. However, Neurotropin administration from 2 to 5 mo had no effect on the immune responses of young animals. Neurotropin administration from 13 to 16 mo restored not only the T-cell proliferation of spleen cells induced by concanavalin A (Con A) and phytohemagglutinin (PHA), but also the interleukin-2 (IL-2) production by spleen cells activated with Con A. However, Neurotropin did not affect the responsiveness of Con A-activated spleen cells to exogenous recombinant IL-2. An absence of suppressor cells capable of inhibiting the IL-2 production in the spleens was confirmed in the 16 mo mice. Neurotropin administration also restored IL-1 production by peritoneal macrophages stimulated with lipopolysaccharide (LPS). These results suggest that long-term administration of Neurotropin restores the decreasing T-cell-dependent immune responses through the recovery of IL-2 and in part IL-1 production, but not the responsiveness to IL-2 in aging BALB/c mice.
Adjuvants, Immunologic↗
True carcinosarcoma of the maxillary sinus.
A case of true carcinosarcoma primarily arising in the right maxillary sinus is reported in a 60-year-old male. His chief complaints were right nasal obstruction and bleeding. Histological findings of the biopsied primary tumor revealed two components of keratinizing squamous cell carcinoma and osteosarcoma which were intricately intermingled. Despite intensive irradiation and chemotherapy, and total maxillectomy, he finally died of rapid tumor recurrence and widely spreading metastases to lungs, pleurae and brain two months later. At autopsy the recurrent and metastatic tumors consisted entirely of the osteosarcoma component, suggesting the efficiency of the radiotherapy and chemotherapy against the carcinomatous component, but not against the sarcomatous one. As for histogenesis, this case was compatible with a combination tumor judging from histologic, immunohistochemical and electron microscopic findings.
Carcinosarcoma↗
Affinity separation of human plasma gelsolin on Affi-Gel Blue.
Human plasma gelsolin was specifically eluted with 1 mM adenosine 5'-triphosphate from an Affi-Gel Blue column. Since the ionic strength of sodium chloride required to elute the protein from the dye column was much higher than that of 1 mM adenosine 5'-triphosphate, the binding of plasma gelsolin with the dye-ligand appeared to be biospecific. Taking advantage of this affinity interaction, we have developed a revised purification method of human plasma gelsolin. The purification included ammonium sulfate precipitation, diethylaminoethyl-Sepharose chromatography, Affi-Gel Blue chromatography, and Phenyl-Sepharose chromatography. The method allowed a reproducible purification of the protein to apparent homogeneity, producing a 331-fold purification with a yield of 6%.
Actins↗
Isolation and characterization of temperature-sensitive mutants of Abelson murine leukaemia virus that exhibit dissociation among morphological transformation, soft agar colony-forming ability and tyrosine kinase activity.
Seven temperature-sensitive (ts) mutants of Abelson murine leukaemia virus (A-MuLV) were isolated on the basis of the temperature dependence of their soft agar colony-forming ability. These seven ts mutants exhibited similar characteristics and were not ts for morphological transformation and autophosphorylation of P120gag-abl protein. The dissociation of the properties of morphology, soft agar colony formation and tyrosine kinase activity might suggest that the v-abl product has more than one primary intracellular target.
Abelson murine leukemia virus↗
Cyclic AMP as a negative regulator of DNA synthesis in FRSK cells, a fetal rat epidermal cell line.
In FRSK cells, a cell line derived from fetal rat epidermal cells, cyclic AMP-elevating agents forskolin (10 microM) and cholera toxin (10 ng/ml) increased cellular cyclic AMP content and suppressed [3H] thymidine incorporation. These effects of forskolin were enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 mM). Dibutyryl cyclic AMP (1 mM), an analog of cyclic AMP, decreased not only basal but also both tumor promoter 12-O-tetradecanoylphorbol-13-acetate- and epidermal growth factor-stimulated [3H] thymidine incorporation. From these results, we suggest that cyclic AMP may be a negative regulatory factor of DNA synthesis in FRSK cells.
1-Methyl-3-isobutylxanthine↗