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M Baba

Publications and source records attributed to M Baba.

At least 271 records · Page 15Linked to original sources
PubMed1997

A novel human CC chemokine PARC that is most homologous to macrophage-inflammatory protein-1 alpha/LD78 alpha and chemotactic for T lymphocytes, but not for monocytes.

By searching the expressed sequence tag (EST) database, we identified partial cDNA sequences encoding a polypeptide with significant sequence identity to the human CC chemokine macrophage-inflammatory protein-1 alpha (MIP-1 alpha)/LD78 alpha. We determined the complete cDNA sequence that contained a reading frame of 89 amino acids with 61% identity to human MIP-1 alpha/LD78 alpha. The mRNA was expressed constitutively at high levels in human lung and at low levels in some lymphoid tissues. Furthermore, the mRNA was strongly induced in several human cell lines, including monocytic U937 cells, by PMA. From these results, we designated this novel CC chemokine as PARC from pulmonary and activation-regulated chemokine. In situ hybridization analyses showed that alveolar macrophages, follicular dendritic cells in the germinal centers of regional lymph nodes, and peripheral blood monocytes stimulated with LPS express PARC mRNA. Using the human CC chemokine yeast artificial chromosome contig that we constructed recently, we mapped the PARC gene (SCYA18) within one of the two subregions of the CC chemokine gene cluster at chromosome 17q11.2. To investigate its biologic activity, the PARC protein was expressed in insect cells. PARC was chemotactic for both activated (CD3+) T cells and nonactivated (CD14-) lymphocytes, but not for monocytes or granulocytes. Binding analysis using PARC fused with alkaline phosphatase-(His)6 showed the presence of a single class of receptors for PARC on lymphocytes with a Kd of 1.9 nM and 590 sites/cell. Thus, PARC is a novel CC chemokine with a close phylogenic relationship with MIP-1 alpha/LD78 alpha, but with a highly selective activity on lymphocytes.

Amino Acid Sequence↗
PubMed1997

d-Limonene inhibits N-nitrosobis(2-oxopropyl)amine induced hamster pancreatic carcinogenesis.

The effect of d-limonene on pancreatic carcinogenesis induced by N-nitrosobis(2-oxopropyl)amine (BOP) was investigated in Syrian golden hamsters. During and after 5 weekly injections of BOP, each hamster was fed diet containing d-limonene. In week 26, quantitative histological analysis showed that prolonged treatment with d-limonene significantly reduced the number of pancreatic carcinomas. Administration of d-limonene did not cause a significant increase in the apoptotic index, but caused a significant decrease in the BrdU labeling index of carcinoma. These findings indicate that d-limonene inhibits the development of pancreatic carcinoma not by enhancing tumor cell loss through apoptosis, but rather by inhibiting cell proliferation.

Animals↗
PubMed1997

Aminopeptidase I is targeted to the vacuole by a nonclassical vesicular mechanism.

The yeast vacuolar protein aminopeptidase I (API) is synthesized as a cytosolic precursor that is transported to the vacuole by a nonclassical targeting mechanism. Recent genetic studies indicate that the biosynthetic pathway that transports API uses many of the same molecular components as the degradative autophagy pathway. This overlap coupled with both in vitro and in vivo analysis of API import suggested that, like autophagy, API transport is vesicular. Subcellular fractionation experiments demonstrate that API precursor (prAPI) initially enters a nonvacuolar cytosolic compartment. In addition, subvacuolar vesicles containing prAPI were purified from a mutant strain defective in breakdown of autophagosomes, further indicating that prAPI enters the vacuole inside a vesicle. The purified subvacuolar vesicles do not appear to contain vacuolar marker proteins. Immunogold EM confirms that prAPI is localized in cytosolic and in subvacuolar vesicles in a mutant strain defective in autophagic body degradation. These data suggest that cytosolic vesicles containing prAPI fuse with the vacuole to release a membrane-bounded intermediate compartment that is subsequently broken down, allowing API maturation.

Aminopeptidases↗
PubMed1997

Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet.

The effect of a purified, high protein diet on enhanced gastric carcinogenesis induced by oral administration of NaCl was investigated in Wistar rats. Rats were fed on a purified diet with an equalized caloric content, containing 8% NaCl and 25% casein (normal protein diet), or 50% casein (high protein diet) after oral treatment with N-methyl-N'-nitro-N-nitrosoguanidine for 25 weeks. In week 52, oral administration of NaCl had significantly increased the incidence and size of gastric cancer in rats fed a normal protein diet. However, NaCl had no significant effect on gastric carcinogenesis in rats fed a high protein diet. Oral administration of NaCl also caused a significant increase in tissue norepinephrine concentrations in the antral portion of the gastric wall, and increased the labeling indices of the antral epithelial cells of rats fed on a normal protein diet. However, in rats fed a high protein diet, administration of NaCl had no significant influence on these two parameters. These findings indicate that a high protein diet attenuates enhanced gastric carcinogenesis induced by the administration of NaCl, and that this effect may be related to its ability to decrease norepinephrine concentrations in the gastric wall, which subsequently decreases the proliferation of antral epithelial cells.

Animals↗
PubMed1997

Enhancement by ethyl alcohol of experimental hepatocarcinogenesis induced by N-nitrosomorpholine.

The effects of ethyl alcohol (EtOH) during or after treatment with N-nitrosomorpholine (NNM) on hepatocarcinogenesis, ornithine decarboxylase (ODC) activity and the labeling index of the liver were investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of 1 g EtOH/kg body weight every other day during or after treatment with NNM. Pre-neoplastic and neoplastic lesions staining positively for glutathione-S-transferase, placental type (GST-P), were examined immunohistochemically. At the end of experiment at week 16, administration of EtOH after NNM treatment had no significant effect on the number and size of GST-P-positive hepatic lesions, whereas administration of EtOH during NNM treatment significantly increased the number and percentage area but not the mean area of GST-P-positive hepatic lesions. EtOH caused significant increases in the ODC activity of the liver and in the labeling indices of enzyme-altered lesions and the adjacent hepatocytes after the cessation of EtOH administration but not during EtOH treatment. Our findings indicate that EtOH enhances hepatocarcinogenesis and suggest that this effect may be closely related to the increases in ODC activity and cell proliferation in enzyme-altered lesions and the adjacent liver after EtOH treatment.

Animals↗
PubMed1997

Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC.

Liver and activation-regulated chemokine (LARC) is a recently identified CC chemokine that is expressed mainly in the liver. LARC functions as a selective chemoattractant for lymphocytes that express a class of receptors specifically binding to LARC with high affinity. To identifiy the receptor for LARC, we examined LARC-induced calcium mobilization in cells stably expressing five CC chemokine receptors (CCR1-CCR5) and five orphan seven-transmembrane receptors. LARC specifically induced calcium flux in K562 cells as well as 293/EBNA-1 cells stably expressing an orphan receptor GPR-CY4. LARC induced migration in 293/EBNA-1 cells stably expressing GPR-CY4 with a bi-modal dose-response curve. LARC fused with secreted alkaline phosphatase (LARC-SEAP) bound specifically to Raji cells stably expressing GPR-CY4 with a Kd of 0.9 nM. Only LARC but not five other CC chemokines (MCP-1, RANTES, MIP-1alpha, MIP-1beta, and TARC) competed with LARC-SEAP for binding to GPR-CY4. By Northern blot analysis, GPR-CY4 mRNA was expressed mainly in spleen, lymph nodes, Appendix, and fetal liver among various human tissues. Among various leukocyte subsets, GPR-CY4 mRNA was detected in lymphocytes (CD4(+) and CD8(+) T cells and B cells) but not in natural killer cells, monocytes, or granulocytes. Expression of GPR-CY4 mRNA in CD4(+) and CD8(+) T cells was strongly up-regulated by IL-2. Taken together, GPR-CY4 is the specific receptor for LARC expressed selectively on lymphocytes, and LARC is a unique functional ligand for GPR-CY4. We propose GPR-CY4 to be designated as CCR6.

B-Lymphocytes↗
PubMed1997

The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4.

Thymus and activation-regulated chemokine (TARC) is a recently identified CC chemokine that is expressed constitutively in thymus and transiently in stimulated peripheral blood mononuclear cells. TARC functions as a selective chemoattractant for T cells that express a class of receptors binding TARC with high affinity and specificity. To identify the receptor for TARC, we produced TARC as a fusion protein with secreted alkaline phosphatase (SEAP) and used it for specific binding. By stably transfecting five orphan receptors and five known CC chemokine receptors (CCR1 to -5) into K562 cells, we found that TARC-SEAP bound selectively to cells expressing CCR4. TARC-SEAP also bound to K562 cells stably expressing CCR4 with a high affinity (Kd = 0.5 nM). Only TARC and not five other CC chemokines (MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cells expressed and secreted), MIP-1alpha (macrophage inflammatory protein-1alpha), MIP-1beta, and LARC (liver and activation-regulated chemokine)) competed with TARC-SEAP for binding to CCR4. TARC but not RANTES or MIP-1alpha induced migration and calcium mobilization in 293/EBNA-1 cells stably expressing CCR4. K562 cells stably expressing CCR4 also responded to TARC in a calcium mobilization assay. Northern blot analysis revealed that CCR4 mRNA was expressed strongly in human T cell lines and peripheral blood T cells but not in B cells, natural killer cells, monocytes, or granulocytes. Taken together, TARC is a specific functional ligand for CCR4, and CCR4 is the specific receptor for TARC selectively expressed on T cells.

Alkaline Phosphatase↗
PubMed1997

Effect of angiogenesis inhibitor TNP-470 on the progression of human gastric cancer xenotransplanted into nude mice.

The effect of an angiogenesis inhibitor, TNP-470, on primary tumor growth, liver metastasis and peritoneal dissemination of gastric cancer was investigated by means of an orthotopic xenotransplanted model of 2 human gastric cancers, MT-2 and MT-5. TNP-470 showed a significant inhibitory effect on the growth of primary tumors after orthotopic transplantation of both xenografts when given at a dose of 30 mg/kg on alternate days from day 7 after transplantation (early treatment). However, growth of the MT-2 primary tumor was not inhibited by administration from day 14 after transplantation (late treatment). Liver metastasis was prevented significantly by early treatment of TNP-470. In particular, early treatment of MT-2 completely inhibited the development of macroscopic foci in the liver and was significantly more effective than late treatment. Peritoneal dissemination also was inhibited. Thus, TNP-470 was revealed to have strong inhibitory activity not only on primary tumors and liver metastases but also against peritoneal dissemination. These results suggest that this agent may provide a new approach to the treatment of gastric cancer.

Adenocarcinoma↗
PubMed1997

Molecular cloning of a novel human CC chemokine EBI1-ligand chemokine that is a specific functional ligand for EBI1, CCR7.

By searching the expressed sequence tag (EST) data base, we identified partial cDNA sequences encoding a novel human CC chemokine. We determined the complete cDNA sequence that encodes a highly basic polypeptide of a total 98 amino acids with 20 to 30% identity to other human CC chemokines. We termed this novel chemokine from EBI1-Ligand Chemokine as ELC (see below). The ELC mRNA was most strongly expressed in the thymus and lymph nodes. Recombinant ELC protein was expressed as a fusion protein with the Flag tag (ELC-Flag). For receptor-binding assays, recombinant ELC protein fused with the secreted form of alkaline phosphatase (SEAP) was used. By stably expressing five CC chemokine receptors (CCR1 to 5) and five orphan receptors, ELC-SEAP was found to bind specifically to an orphan receptor EBI1. Only ELC-Flag, but not MCP-1, MCP-2, MCP-3, eotaxin, MIP-1alpha, MIP-1beta, RANTES (regulated on activation normal T cell expressed and secreted), thymus and activation-regulated chemokine (TARC), or liver and activation-regulated chemokine (LARC), competed with ELC-SEAP for EBI1. ELC-Flag-induced transient calcium mobilization and chemotactic responses in EBI1-transfected cells. ELC-Flag also induced chemotaxis in HUT78 cells expressing endogenous EBI1 at high levels. By somatic hybrid and radiation hybrid analyses, the gene for ELC (SCYA19) was mapped to chromosome 9p13 instead of chromosome 17q11.2 where the genes for CC chemokines are clustered. Taken together, ELC is a highly specific ligand for EBI1, which is known to be expressed in activated B and T lymphocytes and strongly up-regulated in B cells infected with Epstein-Barr virus and T cells infected with herpesvirus 6 or 7. ELC and EBI1 may thus play roles in migration and homing of normal lymphocytes, as well as in pathophysiology of lymphocytes infected with these herpesviruses. We propose EBI1 to be designated as CCR7.

Amino Acid Sequence↗
PubMed1997

Three-drug combination of MKC-442, lamivudine and zidovudine in vitro: potential approach towards effective chemotherapy against HIV-1.

OBJECTIVES: MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil), a potent non-nucleoside reverse transcriptase inhibitor, is a promising candidate for the treatment of HIV-1 infection and is now undergoing clinical trials. We studied the in vitro activity of MKC-442 against HIV-1 replication in a three-drug combination regimen with zidovudine (ZDV) and lamivudine (3TC). METHODS: Drug-drug interactions in MT-4 cells and peripheral blood mononuclear cells (PBMC) infected with HIV-1IIIB were evaluated. The multiple drug effect analysis based on the median effect principle was applied, and the combination indices were calculated using a computer software program. The occurrence of viral breakthrough was investigated during a long-term culture of HIV-1-infected MT-4 cells. RESULTS: When MKC-442 was combined with 3TC and ZDV, they synergistically suppressed HIV-1 replication in MT-4 cells over a wide range of doses irrespective of the endpoints for synergy calculations. Similar results were also obtained in PBMC. An arbitrary combination ratio of 10:100:1 for MKC-442:3TC:ZDV showed stronger synergism than any other ratios examined. As a result of synergy in the three-drug combination, the dose of each drug could be reduced by four- to 24-fold. The three-drug combination markedly delayed or even completely suppressed HIV-1 replication at least for 40 days. Virus emerged in the presence of three drugs at lower doses, although it did not contain any amino-acid mutations in the sequenced reverse transcriptase region and did retain full sensitivity to all three drugs. CONCLUSIONS: Our results demonstrate a potential efficacy of MKC-442 in combination with 3TC and ZDV, and the three-drug combination should be considered for treatment of AIDS patients.

Anti-HIV Agents↗
PubMed1997

Stavudine selectively induces apoptosis in HIV type 1-infected cells.

We evaluated the cytotoxic effects of various human immunodeficiency virus (HIV-1) reverse transcriptase inhibitors (zidovudine, didanosine, zalcitabine, stavudine, and nevirapine) on HIV-1-infected and uninfected T cell lines. Among the compounds, only stavudine (not the others) proved to be more cytotoxic to MOLT-4/IIIB cells (MOLT-4 cells chronically infected with HIV-1) than to uninfected MOLT-4 cells. Its 50% cytotoxic concentrations were 59.8 and 2.2 microM for MOLT-4 and MOLT-4/IIIB cells, respectively. Stavudine was also more cytotoxic to CEM/ROD (CEM cells chronically infected with HIV type 2) than to uninfected CEM cells. Microscopic analysis revealed that stavudine induced apoptosis in MOLT-4/IIIB cells. Apparent chromatin condensation in the nucleus was observed by electron microscopy. Furthermore, a DNA fragmentation ladder was detected by agarose gel electrophoresis. Addition of thymidine to the culture medium could rescue the cells from stavudine-induced apoptosis. The expression of anti-apoptotic protein Bcl-2 was partially downregulated in MOLT-4/IIIB cells after treatment with stavudine. This downregulation was not identified in MOLT-4 cells. These results indicate that stavudine selectively induces apoptosis in HIV-1-infected T cells and may have potential as a novel strategy for effective chemotherapy of the acquired immune deficiency syndrome (AIDS).

Anti-HIV Agents↗
PubMed1997

Lymph node and perinodal tissue tumor involvement in patients with esophagectomy and three-field lymphadenectomy for carcinoma of the esophagus.

BACKGROUND: Lymph node metastasis is a definitive prognostic factor; however, perinodal fat tumor invasion has not been fully elucidated. METHODS: Periesophageal nodes and the surrounding fibrofatty tissue obtained from 131 patients who underwent esophagectomy were examined. RESULTS: Of 9,789 nodes removed, 645 (6.6%) demonstrated invasion and 143 (1.5%) showed perinodal involvement. Of 131 patients 97 (74.0%) had lymph node involvement and 43 (32.8%) had perinodal fat involvement. The incidence of perinodal tissue involvement correlated significantly with the number of nodes involved; 23 (42.6%) of 54 patients with a total of 1-8 nodes involved and 19 (95.0%) of 20 patients with 9 or more involved nodes had perinodal involvement. The 5-year survival for 33 patients without involved nodes or perinodal tissue extension was 59.7%, compared to 14.0% for 43 patients with perinodal fat involvement. CONCLUSION: Perinodal tissue carcinoma into the periesophageal fibrofatty tissue was a decisive prognostic factor in patients with curative resection for esophageal carcinoma.

Adipose Tissue↗
PubMed1997

Monoclonal antibodies to purified cortical Lewy bodies recognize the mid-size neurofilament subunit.

Lewy bodies (LBs) are filamentous intraneuronal inclusions that are hallmark lesions of Parkinson's disease, and LBs have been shown, by immunohistochemistry, to contain cytoskeletal as well as other cellular proteins. Similar LBs also occur in the cortical neurons of a subset of patients with Alzheimer's disease (AD), and cortical LBs are the predominant or sole lesions in the brains of patients with an AD-like dementia known as diffuse Lewy-body disease (DLBD). To gain insight into the biochemical composition of LBs, we generated monoclonal antibodies (mAbs) to LBs purified from the brains of patients with DLBD. Here, we describe three of these new mAbs (LB48, LB202, and LB204) that stained LBs by immunohistochemistry and recognized the medium molecular mass neurofilament (NF) protein in western blots. These results support the hypothesis that NF subunits are integral components of LBs. Continued efforts to clarify the composition of LBs are likely to lead to novel strategies for the antemortem diagnosis of LB disorders as well as to insight into the role LBs play in the degeneration of affected neurons in these disorders.

Antibodies, Monoclonal↗
PubMed1997

HTLV-I-infected T cells activate autologous CD4+ T cells susceptible to HTLV-I infection in a costimulatory molecule-dependent fashion.

A vigorous production of human T lymphotropic virus type I (HTLV-I)-infected CD4+ T cells is closely associated with the development of adult T cell leukemia (ATL) and neurological disease. However, the immunological mechanisms leading to generation of the HTLV-I-infected cells are not fully clarified. The modulation of CD80 and CD86 expression on the HTLV-I-infected cells and its physiological role in the interaction of infected CD4+ T cells with uninfected CD4+ T cells was examined. The HTLV-I-infected CD4+ T cell lines established from ATL patients and normal donors by infecting their CD4+ T cells with the virus expressed CD80, CD86, and HLA-DR, and induced a proliferation of autologous and allogenic CD4+ T cells. While the CD4+ T cells stimulated with the autologous HTLV-I-infected cells for 7 days expressed CD80 and CD86 but not HTLV-I gene products, they expressed HTLV-I gag antigen after 4 weeks. The interaction of HTLV-I-infected and -uninfected CD4+ T cells was profoundly suppressed by a combination of CD80 and CD86 monoclonal antibodies. These results suggest that the induction of CD80 and CD86 on HTLV-I-infected CD4+ T cells participates actively in the generation of the virus-infected progenitor cells.

Antibodies, Monoclonal↗
PubMed1997

Comparison of p53 expression in proximal and distal gastric cancer: histopathologic correlation and prognostic significance.

BACKGROUND: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. METHODS: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. RESULTS: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p < 0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. CONCLUSION: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.

Adult↗
PubMed1997

Enhancement by monochloramine of the development of gastric cancers in rats: a possible mechanism of Helicobacter pylori-associated gastric carcinogenesis.

The effects of cytotoxic monochloramine on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in Wistar rats. After oral administration of drinking water containing the carcinogen and regular chow pellets for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without s.c. injection of taurine, until the end of the experiment in week 52. Treatment with both ammonium acetate and sodium hypochlorite significantly increased the incidence of gastric cancers in week 52, while the concomitant use of taurine with ammonium acetate and sodium hypochlorite significantly attenuated the enhanced gastric carcinogenesis. Spectrophotometric examinations revealed that taurine scavenged monochloramine. These findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be mediated by monochloramine.

Animals↗
PubMed1997

HIV-1-infected myelomonocytic cells are resistant to Fas-mediated apoptosis: effect of tumor necrosis factor-alpha on their Fas expression and apoptosis.

To get insight into the involvement of tumor necrosis factor-alpha (TNF-alpha) and Fas (CD95) ligand in apoptosis (programmed cell death) of monocyte/macrophages in HIV-1-infected individuals, various T cell and myelomonocytic cell lines, including the HIV-1-infected clones OM-10.1 and U1 cells, were cultured in the presence of either TNF-alpha alone, anti-Fas agonist monoclonal antibody (Fas-mAb) alone, or their combinations. TNF-alpha moderately decreased the viability of myelomonocytic cell lines in a dose-dependent fashion (1-100 ng/ml). Unlike HIV-1-infected T cell lines, the viability of OM-10.1 and U1 cells was not affected by the treatment with Fas-mAb alone at concentrations up to 1,000 ng/ml. However, the viability of OM-10.1 cells further decreased with increasing concentrations of Fas-mAb when exposed simultaneously to TNF-alpha, suggesting that TNF-alpha sensitizes the cells to Fas-mAb-induced cell death. FACScan analysis and DNA gel electrophoresis revealed that the cell death was due to apoptosis. Such an effect of Fas-mAb was not identified in U1 cells. TNF-alpha but not Fas-mAb activated latent HIV-1 in OM-10.1 and U1 cells. Although all myelomonocytic cell lines expressed Fas on their cell surface, TNF-alpha significantly up-regulated the expression of Fas in only OM-10.1 cells. These results indicate that, unlike T cells, HIV-1-infected myelomonocytic cells are generally resistant to the Fas-mediated apoptosis. However, they would become sensitive to the apoptosis if the expression of Fas could be up-regulated by TNF-alpha or other factors.

Antibodies, Monoclonal↗