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Biomedical subjects

G Suzuki

Publications and source records attributed to G Suzuki.

At least 73 records · Page 4Linked to original sources
PubMed1997

Multistage regulation of Th1-type immune responses by the transcription factor IRF-1.

Eradication of a given pathogen is dependent on the selective differentiation of T helper (Th) cells into Th1 or Th2 types. We show here that T cells from mice lacking the transcription factor IRF-1 fail to mount Th1 responses and instead exclusively undergo Th2 differentiation in vitro. Compromised Th1 differentiation is found to be associated with defects in multiple cell types, namely impaired production of interleukin-12 by macrophages, hyporesponsiveness of CD4+ T cells to interleukin-12, and defective development of natural killer cells. These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.

Animals↗
PubMed1997

A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt's type (FAB-L3) leukemia.

We report a case of B-cell acute lymphocytic leukemia which showed histological transformation from an FAB-L2 into a Burkitt's type (FAB-L3). Both leukemias had identical immunoglobulin heavy-chain joining gene and kappa light-chain joining gene rearrangements, indicating the clonal identity of the two leukemias. A chromosomal analysis of leukemia cells on the onset indicated normal karyotype, whereas that of the transformed FAB-L3 showed t(8;14)(q24;q32). Furthermore, the proto-oncogene c-myc was in the germline configuration in the initial leukemia but in the rearranged configuration after transformation. Presence of t(8;14)(q24;q32) and the c-myc gene rearrangement after transformation suggested that the chromosomal translocation followed by the activation of the c-myc proto-oncogene might be involved in the Burkitt's type transformation of the FAB-L2 leukemic clone, but not in the leukemogenesis of the initial FAB-L2 leukemia.

Adolescent↗
PubMed1997

[Positive seroconversion syphilis in a patient with acute lymphocytic leukemia after allogeneic bone marrow transplantation].

An acute lymphocytic leukemia patient underwent allogeneic bone marrow transplantation (BMT) from a sibling who was serologically positive for syphilis. After the donor was administered antibiotic therapy, the titration of treponema pallidum hemagglutination (TPHA) decreased from x1260 to x320. Thereafter, the graft consisting of mononuclear cells was transplanted. TPHA of the recipient turned positive on day +63, but became negative 1.5 years after BMT. Although the cause of the seroconversion of TPHA seemed to be the contamination of treponema to the graft, the adoptive transfer could not be ruled out as an another possible cause.

Adult↗
PubMed1996

In vivo induction of cytotoxic T lymphocytes specific for a single epitope introduced into an unrelated molecule.

Cytotoxic T lymphocytes (CTLs) recognise antigenic peptides in the context of major histocompatibility complex (MHC) class I molecules on virus-infected cells. The formation and transportation of antigenic peptides to class I MHC in the cells are multi-step reactions known as antigen processing. In order to design a good DNA vaccine, it is important to dissect the specificity of antigen processing. Here we describe the construction of an epitope-based plasmid vector as a device to investigate antigen processing in transfected cells. The epitope-based plasmid vector was constructed by insertion of an epitope-encoding minigene into the lacZ gene. We used a CTL epitope on influenza A virus nucleoprotein (NP366-374 epitope) as a model. Upon transfection, the epitope-based plasmid vector induced the expression of NP epitope antigenically as well as immunogenically. Immunization of mice with plasmid-transfected cells was able to induce NP epitope-specific CTLs in vivo. Moreover, the plasmid vector functioned as a gene vaccine; NP epitope-specific CTLs were primed in vivo upon transfection of the vector into dermis by electroporation. The results suggest that this epitope-based DNA delivery system may provide a new strategy for in vivo induction of epitope-specific CTLs to investigate antigen processing and presentation.

Amino Acid Sequence↗
PubMed1996

Expression cloning of a cDNA for human ceramide glucosyltransferase that catalyzes the first glycosylation step of glycosphingolipid synthesis.

We have isolated a cDNA encoding human ceramide glucosyltransferase (glucosylceramide synthase, UDP-glucose:N-acylsphingosine D-glucosyltransferase, EC 2.4.1.80) by expression cloning using as a recipient GM-95 cells lacking the enzyme. The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis and the product, glucosylceramide, serves as the core of more than 300 glycosphingolipids. The cDNA has a G+C-rich 5' untranslated region of 290 nucleotides and the open reading frame encodes 394 amino acids (44.9 kDa). A hydrophobic segment was found near the N terminus that is the potential signal-anchor sequence. In addition, considerable hydrophobicity was detected in the regions close to the C terminus, which may interact with the membrane. A catalytically active enzyme was produced from Escherichia coli transfected with the cDNA. Northern blot analysis revealed a single transcript of 3.5 kb, and the mRNA was widely expressed in organs. The amino acid sequence of ceramide glucosyltransferase shows no significant homology to ceramide galactosyltransferase, which indicates different evolutionary origins of these enzymes.

Amino Acid Sequence↗
PubMed1996

Induction of a novel cytochrome P450 (CYP93 family) by methyl jasmonate in soybean suspension-cultured cells.

We isolated a cDNA encoding a novel cytochrome P450 (CYP93A1) from soybean suspension-cultured cells that had been treated with methyl jasmonate (MeJA). The amino acid sequence of the gene product had 30-40% identity with those of other plant P450s. The protein contained the heme-binding domain which is highly conserved among plant P450s. Transcription of the cytochrome P450 gene in soybean cells was induced by 30 microM MeJA even in the presence of cycloheximide, and reached maximum level 6 h after MeJA treatment. This is the first report of a plant cytochrome P450 gene whose transcription is induced by MeJA even without protein synthesis.

Acetates↗
PubMed1996

Genetic mapping of the mouse stromal cell-derived factor gene (Sdf1) to mouse and rat chromosomes.

Stromal cell-derived factor 1 (SDF1) is a new member of the Cys-X-Cys chemokine family. The chromosomal location of Sdf1, the gene coding mouse SDF1, was determined by fluorescence in situ hybridization (FISH) and molecular linkage analysis. The mouse Sdf1 gene was localized to the R-band-positive F1 band of chromosome 6 by direct R-banding FISH. Interspecific backcross analysis identified the mouse Sdf1 gene locus at 0.8 cM terminal to D6Nit55 and 3.0 cM proximal to D6Mit12. With in situ hybridization using a mouse cDNA clone as a probe, the rat Sdf1 gene was localized to the R-band-positive band 4q42.1, where conserved linkage homology to mouse chromosome 6 has been identified. Although other Cys-X-Cys chemokine genes have been mapped on human chromosome 4, the chromosomal segment where the mouse and rat Sdf1 gene reside have no conserved linkage homology to human chromosome 4. This result suggests that SDF1 is a new chemokine class.

Amino Acid Sequence↗
PubMed1996

[Transverse lesion of the spinal cord due to mucormycosis in an AML patient].

A 54 year old man complained exertional dyspnea and palpitation since November 1989. As he was diagnosed with marked anemia, leukocytosis and thrombocytopenia by his work place doctor, he was admitted to our hospital. Acute myelogenous leukemia was diagnosed based on laboratory findings. BHAC-DMP, BHAC-MEP and A triple V therapies were only partially effective. Fine nodular shadows in all lung fields and a semicircular mass in the right lower lobe next to the thoracic vertebra were evident on the chest X-P since the end of March 1990. He was treated with antibiotics and amphotericin B but the abnormal lung shadows did not disappear. He had sudden onset of paraplegia and loss of all sensation below Th6 on May 1. Aparavertebral mass in the right lower lobe was detected by CT and MRI, for which radiotherapy was performed but without improvement. He died of respiratory failure on May 12. Autopsy showed that the semicircular paravertebral mass continued to the main pulmonary vein and epidural area of the thoracic cord (Th6-8). Microscopically, mucormycosis was found. Necrosis due to mucor embolism was found in the thoracic cord. It is usually difficult to diagnose mucormycosis in immunocompromised patients while they are alive. It is important to suspect mucormycosis if any infarction symptoms or infections resistant to antibiotics develop in immunocompromised patients.

Fatal Outcome↗
PubMed1996

[Treatment of refractory hematologic malignancies by combination of cytarabine ocfosfate and etoposide].

We attempted a combination chemotherapy with cytarabine ocfosfate (SPAC) and etoposide for myelodysplastic syndrome (MDS), and acute non-lymphocytic leukemia developing after a prior history of MDS (MDS/ANLL). SPAC and etoposide were administered orally at the dose of 200 mg/day and 25 mg/day for 14 days, as standard regimen. Two cases complete remission (CR), 4 of partial remission (PR) were obtained among 9 patients. The plasma concentration of cytarabine (Ara-C) reached a plateau at around 4.5 ng/ml during the treatment period from the 7th to the 14th day, and it was detectable with a gradual decrease until the 28th day in spite of the last administration of SPAC on the 14th day. It is suggested that this combination chemotherapy is useful against MDS, MDS/ANLL and other resistant leukemia, especially in elderly patients who can not be treated by intensive combination chemotherapy.

Acute Disease↗
PubMed1996

[Two cases of relapse or refractory germ cell tumor who had been treated with combination chemotherapy of cisplatin and carboplatin].

We tried a combination chemotherapy with cisplatin (CDDP) and carboplatin (CBDCA) (CDDP/CBDCA regimen) as salvage therapy for 2 cases with recurrent or refractory Germ Cell Tumor (GCT). Case 1 was a 29-year-old man with 2nd relapsed embryonal carcinoma and seminoma originating from testis. Case 2 was a 23-year-old man with primary refractory embryonal carcinoma and yolk sac tumor originating from mediastinum. CDDP and CBDCA were administered at the dose of 120 mg/m2 and 350 mg/m2 on day 1, and vinblastin was administered at the dose of 10 mg/body on day 2. In one of two cases, a complete response was obtained. Non-hematologic toxicity of CDDP/CBDCA regimen was tolerable. It is suggested that this combination chemotherapy is useful for GCT recurrence.

Adult↗
PubMed1995

IL-1 induces expression of WAF1 mRNA in human fibroblasts: mechanisms of accumulation.

WAF1 inhibits cyclin-cyclin dependent kinase complexes, causing arrest in the cell cycle. We report that interleukin-1 (IL-1) regulates the levels of WAF1 protein and mRNA in human fibroblasts. Further studies showed that 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhanced the accumulation of WAF1; cells refractory to TPA still increased their levels of WAF1 mRNA when exposed to IL-1. IL-1 also increased transcription of WAF1 by 13-fold and WAF1 mRNA became 2-fold more stable in cells stimulated with IL-1 (t1/2 = 2 h) as compared to untreated cells (t1/2 = 1 h). In summary, IL-1 induces expression of WAF1, and this occurs by increased transcription of WAF1 and stabilization of WAF1 mRNA. Our data also indicate that the induction of WAF1 mRNA by IL-1 occurs through a pathway independent of protein kinase C activation.

Cell Line↗
PubMed1995

Administration of recombinant human IL-1 by Staphylococcus enterotoxin B prevents tolerance induction in vivo.

Peripheral tolerance is important to prevent autoimmunity of T cells against tissue-specific autoantigens in peripheral organs. In certain pathologic situations, peripheral tolerance breaks for unknown reasons and autoimmune diseases occur. Anergy is one of the mechanisms of peripheral tolerance that down-modulates IL-2 synthesis and IL-4 responsiveness by helper T cell clones. In this report, we utilized a model system in which V beta 8+ CD4 T cells were anergized by administration of high doses of Staphylococcus enterotoxin B (SEB) in vivo and investigated an effect of recombinant human (rh) IL-1 on the tolerance induction. RhIL-1 was used because of its ability to induce IL-4 responsiveness in T cells. When rhIL-1 was administered within 24 h after SEB inoculation, the cytokine interfered with tolerance induction; V beta 8+CD4 T cells from mice that had been treated with both SEB and IL-1 proliferated in response to SEB and produced IL-2, IL-4, and IFN-gamma upon TCR/CD28 cross-linking. Delayed administration of rhIL-1 by 48 h failed to do this; T cells did not proliferate in response to SEB, but they retained an ability to produce IL-4 upon TCR/CD28 cross-linking. Administration of rhIL-1 induced better proliferation of V beta 8+CD4 T cells in response to SEB in vivo but did not prevent cell death after proliferation. These results suggest a potential role of inflammatory cytokine IL-1 in the course of autoimmunity via interference with tolerance.

Animals↗
PubMed1995

Irradiation induces WAF1 expression through a p53-independent pathway in KG-1 cells.

WAF1 binds to cyclin-Cdk complexes and inhibits their activity, causing cell cycle arrest. Previous studies have shown that expression of WAF1 is induced through the p53-dependent pathway; WAF1 is induced in cells with functional p53 but not in cells with either mutant p53 or no 53. Human myeloblastic leukemia cells KG-1 had no constitutive expression of p53, and irradiation did not induce p53. However, irradiation increased WAF1 expression in KG-1 cells and other cell lines containing mutant p53. The KG-1 cells constitutively produced low levels of tumor necrosis factor (TNF); irradiation markedly increased the production of TNF. Notably, induction of WAF1 mRNA by irradiation was blocked by anti-TNF antibody. Furthermore, exogenously added TNF increased levels of WAF1 mRNA in these cells. Irradiation increased the rate of WAF1 transcription 3-fold, and the half-life (t1/2) of WAF1 mRNA in these cells increased from < 1 h in unirradiated cells to > 4 h in irradiated cells. These findings indicate that increased levels of WAF1 transcripts occur, at least in part, through a pathway of TNF production and that the increase in WAF1 mRNA observed after irradiation is regulated by both transcriptional and posttranscriptional mechanisms. Our present study strongly suggests that an alternative pathway of induction of WAF1 occurs independent of activation by p53.

Cell Line↗
PubMed1995

Irradiation increases manganese superoxide dismutase mRNA levels in human fibroblasts. Possible mechanisms for its accumulation.

Irradiation induces the production of superoxide radicals (O2.-), which play an important causative role in radiation damage. Manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme involved in scavenging O2..-. This study examined MnSOD gene regulation by irradiation in WI38 human fibroblasts. Unstimulated fibroblasts constitutively expressed MnSOD activity and mRNA; irradiation markedly increased MnSOD activity and mRNA levels. The increase in MnSOD transcripts by irradiation was both time- and dose-dependent. WI38 fibroblasts constitutively produce low levels of interleukin-1 (IL-1). The induction of MnSOD mRNA by irradiation was partially blocked by anti-IL-1 antibodies, and treatment of cells with IL-1 also increased MnSOD mRNA levels. Inhibition of the cyclo-oxygenase pathway with indomethacin augmented the induction MnSOD mRNA by irradiation and prostaglandin E2 inhibited the accumulation of MnSOD mRNA by irradiation. Transcriptional run-on analysis showed that irradiation increased the rate of MnSOD transcription 2-fold. Stability studies of MnSOD mRNA in these cells showed that the half-life increased from < 1.5 h in unirradiated cells to > 4 h in irradiated cells. These results suggest that induction of the MnSOD gene after irradiation is regulated, at least in part, by IL-1 production and that increased levels of MnSOD transcripts also occur through a pathway of endogenous prostaglandin E2 production. Our data indicate that the increase in MnSOD mRNA observed after irradiation occurs through both transcriptional and post-transcriptional mechanisms.

Cells, Cultured↗
PubMed1995

Immune response to hepatitis C virus core protein in mice.

To analyse the immune response to the hepatitis C virus (HCV) core protein, we immunized mice with the protein. BALB/c (H-2d) and C3H/He (H-2k) mice were high responders, while C57BL/6 (H-2b) mice were low responders in terms of Th cell proliferative responses. All the strains showed comparable levels of antibody responses to the HCV core protein. The Th cell lines recognized residues 61-90 of the HCV core protein in the context of I-Ad (BALB/c) and residues 11-30 in the context of I-Ek (C3H/He), respectively. The Th cell lines were restricted by I-Ab in C57BL/6 mice but recognized no synthetic peptide that spanned the region, although derivative clones from the line recognized residues 1-20 and 91-110 of the HCV core protein, respectively. The Th cell lines were Th 1 subset in all three strains based on the profile of lymphokine secretion. The major B cell epitope of the protein was found to be within residues 21-40 of the HCV core protein in all three strains. These observations should be useful for better understanding of the immune response to the HCV core protein in vivo.

Amino Acid Sequence↗