Detection of serum p53 antibodies in mucosal esophageal cancer and negative conversion after treatment.
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Aged↗
Biomedical subjects
T Ochiai
Publications and source records attributed to T Ochiai.
Impact of preoperative serum carcinoembryonic antigen, CA 19-9 and alpha fetoprotein levels in gastric cancer patients.
The relationship between preoperative serum carcinoembryonic antigen (CEA), CA 19-9 and alpha-fetoprotein (AFP) levels and their clinicopathological features were evaluated in gastric cancer patients. The positive rates of CEA, CA 19-9 and AFP were 24.8, 27.6 and 12.7%, respectively. Gastric cancer with deeper tumor invasion was significantly more common among patients positive for these tumor markers. Patients with positive CEA or CA 19-9 values had a significantly high risk of lymph node metastases (p = 0.045 and p = 0.002, respectively). Synchronous liver metastases was more commonly found in patients with a positive CA 19-9 value. A significant difference (p < 0.001) in survival rate was found between patients with positive CA 19-9 values and those with negative values. CA 19-9 is useful for the prognosis of gastric cancer patients, whereas CEA, although unsuitable for prognosis, contributes to the prediction of cancer invasion.
Adult↗
Interactive mechanisms among pituitary adenylate cyclase-activating peptide, vasoactive intestinal peptide, and parathyroid hormone receptors in guinea pig cecal circular smooth muscle cells.
Vasoactive intestinal peptide (VIP) causes relaxation of smooth muscle cells via both VIP-specific receptor coupled to nitric oxide synthase and VIP-preferring receptor coupled to adenylate cyclase. Because the mechanism of interaction among VIP, pituitary adenylate cyclase-activating peptide (PACAP), and PTH is still unclear, the characteristics of the receptors for PACAP and PTH in circular muscle cells obtained from the guinea pig cecum were investigated. The effects of an inhibitor of cAMP-dependent protein kinase [cyclic adenosine 3',5'-monophosphorothioate (Rp-cAMPS)], guanylate cyclase inhibitors, antagonists of these peptides, and the selective receptor protection on the relaxing effect produced by PACAP, VIP, and PTH were examined. PACAP-induced relaxation was significantly inhibited by a VIP antagonist, a PTH antagonist, Rp-cAMPS, and an inhibitor of particulate guanylate cyclase. VIP-induced relaxation was significantly inhibited by a PACAP antagonist and a PTH antagonist. PTH-induced relaxation was significantly inhibited by a VIP-specific receptor antagonist and Rp-cAMPS, but not by a PACAP antagonist. A PTH antagonist significantly inhibited a VIP-preferring receptor agonist-induced relaxation. The muscle cells in which cholecystokinin octapeptide and PTH receptors were protected completely abolished the inhibitory responses to VIP and PACAP. The muscle cells in which cholecystokinin octapeptide and VIP or PACAP receptors were protected completely abolished the inhibitory response to PTH. This study shows that PACAP induces relaxation of these muscle cells via both VIP-preferring receptor coupled to adenylate cyclase and PACAP-specific receptor, and that PTH induces relaxation of the muscle cells via PTH-specific receptor coupled to adenylate cyclase. In addition, the results of a selective receptor protection show that PTH does not bind to VIP receptors, and that VIP does not bind to PTH receptor. Therefore, this study first demonstrates the presence of one-way inhibitory mechanisms from the PTH-specific receptor to the VIP-preferring receptor, and from the VIP-specific receptor to the PTH-specific receptor in the mechanisms of interaction between VIP and PTH.
Animals↗
Induction of antitumor effect on human esophageal carcinoma cells by the retroviral expression of granulocyte macrophage-colony stimulating factor gene.
We have examined antitumor effect of human esophageal carcinoma cells (T.Tn) which were retrovirally transduced to express mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) gene. Nude mice inoculated with T.Tn cells secreting mGM-CSF developed small tumors but the tumors regressed spontaneously, although the proliferation in vitro of transduced cells was not different from that of wild-type cells. In contrast, the tumor of T.Tn cells transduced with human GM-CSF grew as that of wild-type cells, since murine GM-CSF receptors do not bind to human GM-CSF. Histological examination of the regressing tumor of mGM-CSF-producing T.Tn cells revealed predominant infiltration of inflammatory cells including macrophages. In addition, local injection of mGM-CSF-producing T.Tn cells into the established wild-type tumors significantly induced the retardation of subsequent wild-type tumor growth, suggesting that T-cell independent local response plays a crucial role in destroying tumor cells.
Animals↗
Antitumor response of genetically engineered IL-2 expression to human esophageal carcinoma cells in mature T cell-defective condition.
We examined whether antitumor effect could be produced by retrovirally expressed human interleukin-2 (hIL-2) gene in human esophageal cancer cells (T.Tn) using immunocompromised nude mice. Loss of tumorigenicity of hIL-2-producing T.Tn (T.Tn/hIL-2) cells inoculated subcutaneously was observed in contrast to continuous tumor growth of wild-type cells, although in vitro proliferation of T.Tn/hIL-2 cells remained the same as that of wild-type cells. The antitumor effect was also evidenced by the injection of T.Tn/hIL-2 cells into established tumors of wild-type cells. The injection significantly retarded the subsequent growth of wild-type tumors. Histological examination of regressing T.Tn/hIL-2 cells revealed necrotic areas and infiltration of several types of inflammatory cells. Treatment of nude mice with anti-asialoGM1 antibody did not influence the IL-2-mediated tumor rejection. Vaccination of nude mice with irradiated T.Tn/hIL-2 cells whose secretion of hIL-2 in amount was comparable to that of unirradiated cells did not develop protective immunity. Taken together, the antitumor effect achieved in nude mice by the inoculation of T.Tn/hIL-2 cells is mediated by non-T non-natural killer cells.
Animals↗
Water purification system by using the biofilter for long-term experiment equipment with aquatic animals for the space station.
We have developed a water purification system that enables long-term experiment with aquatic animals for 90 days or more on the space station. We designed the system that combined a biofilter for ammonia removal (nitrification) with another for nitrate removal (denitrification). The experiment with goldfish was for 90 days with an aquatic animals' examination device. The equipment consists of a fish tank, a filter module, pumps, and an artificial lung for gas exchange. The goldfish were kept in the tank without any water replacement throughout the experiment. When a filter module consists of adsorbents without bacteria, the concentration of the nitrite and ammonia begin to increase so that the goldfish die. On the contrary, neither ammonia nor nitrite accumulated throughout the experiment, and the concentration of T-N also maintained 30 ppm or less when the combined biofilter was used. Moreover, no fish died throughout the period. The water purification system with biofilter enabled us to examine the long-term life support testing. We also report a new denitrification (correction of dentrification) method for the life support system.
Animals↗
Chemical modification of amino acid residues in glycerinated Vorticella stalk and Ca(2+)-induced contractility.
The glycerinated stalk of the peritrich ciliate Vorticella, was treated with various reagents to chemically modify the amino acid residues. The influences of these modifcations on spasmoneme contractility were investigated. First, it was confirmed that the spasmoneme contraction is not inhibited by alteration of SH groups. It was also demonstrated that chemical modification of methionine and tryptophan residues abolishes spasmoneme contractility. The reagents used for chemical modification were N-bromosuccinimide (NBS), chloramine T, and 2-hydroxy-5-nitrobenzyl bromide (HNBB), which abolished spasmoneme contractility at concentrations of 40-50 microM, 200-300 microM, and 4 mM, respectively. These results suggest that, along with Ca2+ binding proteins, there are other as yet to be identified proteins involved in contractility.
2-Hydroxy-5-nitrobenzyl Bromide↗
Advances in the development of immunosuppressive agents in organ transplantation.
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Graft Rejection↗
The characterization of reconstituted passenger leukocytes on the induction of tolerance in rat liver transplantation.
The tolerance induced by orthotopic liver transplantation [DA (RT1a) rats to PVG (RT1c) rats] can be prevented by total body irradiation of the donor rat. Reconstitution of the irradiated donor with DA splenic leukocytes reintroduces this tolerance. To investigate the major histocompatibility complex (MHC) specificity of passenger leukocytes, irradiated DA donors were reconstituted by third-party BN (RT1n) splenic leukocytes. The reconstitution with BN splenocytes re-established DA-specific tolerance in PVG recipients, as confirmed by subsequent DA cardiac allografting, while BN hearts were rejected with second-set tempo. To determine which cell components play an important role in re-establishing liver graft tolerance, DA splenic leukocytes were further purified into three types: T, B, and adherent cells. Only "T-cell-enriched" preparations restored liver graft tolerance in three out of five PVG recipients. These results suggest that passenger leukocytes of differing MHC types can help to induce liver-specific tolerance and that T cells in the liver graft may be essential to regulate tolerance induction.
Animals↗
Direct inhibitory effect of adrenomedullin and guanylin on isolated caecal circular smooth muscle cells of guinea pig.
Smooth muscle cells isolated from the caecal circular smooth muscle layers of the guinea pig were used to determine whether adrenomedullin and guanylin can inhibit the contractile response produced by 10(-9) M cholecystokinin octapeptide (CCK-8). In addition, to elucidate each intracellular mechanisms, we examined the effects of an inhibitor of cAMP-dependent protein kinase, an inhibitor of particulate guanylate cyclase, and an inhibitor of soluble guanylate cyclase on the adrenomedullin- or guanylin-induced relaxation of the caecal circular smooth muscle cells. Both adrenomedullin and guanylin inhibited the contractile response produced by CCK-8 in a dose-dependent manner, with IC50 values of 0.12 nM and 2.4 pM, respectively. An inhibitor of cAMP-dependent protein kinase significantly inhibited the relaxation produced by adrenomedullin. In contrast, an inhibitor of particulate guanylate cyclase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the relaxation produced by adrenomedullin. On the other hand, an inhibitor of particulate guanylate cyclase significantly inhibited the guanylin-induced relaxation, although an inhibitor of cAMP-dependent protein kinase and an inhibitor of soluble guanylate cyclase did not have any significant effect on the guanylin-induced relaxation. In this study, we first demonstrated the direct inhibitory effects of adrenomedullin via cAMP system and guanylin via particulate guanylate cyclase system on the isolated caecal circular smooth muscle cells.
Adrenomedullin↗
Protease-induced multicell formation in Staphylococcus haemolyticus.
Multicellular cells were efficiently induced in Staphylococcus haemolyticus by the addition of protease to exponentially growing cultures at 30 C. Electron microscopy revealed the formation of tetrad-shaped multicells that were septated but not separated from each other. Incubation of the multicells with extract from the cells grown without protease resulted in a fourfold increase in the number of colony-forming units as compared with the untreated control. An electrophoretic analysis showed that protease caused a loss of cell wall-lytic activity of the cell, which possibly led to the formation of multicells through cessation of cross wall separation.
Cell Division↗
Relationship between cellular ATP content and cellular functions of primary cultured rat hepatocytes in hypoxia.
The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo, perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 x 10(4) and 5 x 10(4) cells/0.18 mL per cm2 for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis.
Adenine Nucleotides↗
Leech extracellular hemoglobin: two globin strains that are akin to vertebrate hemoglobin alpha and beta chains.
Leech (Whitmania edentula, Haemadipsa zeylanica var. japonica and Erpobdella lineata) extracellular hemoglobins are basically composed of three constituent subunits, a dimer (D1 and D2 chains) and two monomers (M1 and M2 chains). We isolated these four chains from respective species by a combination of reversed-phase chromatography on a Resource RPC column and gel-filtration on a Superdex 75 column. The apparent molecular masses of the four globin chains were estimated by SDS-PAGE analysis to be 13 kDa (M1), 16 kDa (M2; 19 kDa in its reduced form) and about 27 kDa for the dimer subunit (13 kDa for D1; 15 kDa for D2), regardless of the source. The amino (N)-terminal segments (21-30 residues) from twelve globin chains of the above three species were determined and aligned. It was found that the twelve sequences could be separated into two distinct globin groups A and B. This finding supports the original idea of "two globin strains in annelid hemoglobin", which was proposed without any evidence for leech hemoglobins. Comparing the sequences in the three classes of Annelida, Hirudinea, Oligochaeta and Polychaeta, we found two invariant amino acids, Cys and Trp, which are interposed by eleven amino acid residues. Furthermore, the globin chains belonging to strain A were readily discernible as they had three more invariants, Ser-13, Asp-16 and Trp-28, while the globin chains of strain B had two more invariants, Lys-12 and Arg-27. Consequently, we propose that each of the three classes of Annelida have two distinct groups of globin chains that are akin to vertebrate hemoglobin alpha and beta chains.
Amino Acid Sequence↗
Symptomatic porphyria secondary to hepatocellular carcinoma.
A 58-year-old woman gave a 6-month history of porphyria-like photosensitivity. Fractioned porphyrin analysis by high performance liquid chromatography revealed elevated concentrations of all urinary porphyrins and faecal protoporphyrin. Hepatocellular carcinoma had developed in an otherwise normal liver. Tumour tissue fluoresced strongly under fluorescence microscopy, exhibiting elevated activity of three haem-biosynthetic enzymes, delta-aminolevulinic acid (ALA) synthase. ALA dehydratase and porphobilinogen deaminase. This patient did not satisfy any of the criteria for inherited porphyria. The patient's symptoms were relieved after excision of the liver tumour. This strongly suggests that excessive porphyrin synthesis originated from the tumour tissue. Primary porphyria-like photosensitivity occurs as a paraneoplastic phenomenon, secondary to hepatocellular carcinoma.
Carcinoma, Hepatocellular↗
Inhibition of peritoneal dissemination of colon carcinoma in syngeneic mice immunized with interleukin-2-producing cells.
We have examined the antitumor effect of murine colon carcinoma cells engineered to produce human interleukin-2 (IL-2) in syngeneic mice. Subcutaneous inoculation of retrovirally-transduced cells with IL-2 gene formed small tumors, but they became regressed spontaneously. Consequently, the inoculated mice showed prolonged survival. Histological examination of the tumors derived from IL-2-producers revealed predominant infiltration of macrophages around tumor necrotic masses. Thus, inoculation of IL-2-producing cells could protect the mice from subsequent subcutaneous or intraperitoneal challenges with wild-type cells, suggesting the induction of acquired immunity due to the effect of tumor vaccination.
Animals↗
Antitumor effect induced by the expression of granulocyte macrophage-colony stimulating factor gene in murine colon carcinoma cells.
Murine colon carcinoma cells which secrete several kinds of cytokine after retroviral transduction with corresponding genes, were examined for their antitumor effects in syngeneic mice. The mice inoculated with granulocyte macrophage-colony stimulating factor (GM-CSF) producer cells showed not only prolonged survival but also reduced tumorigenicity. The antitumor effect caused by the expression of interleukin-4 was less than that of GM-CSF, and interleukin-6 producer cells did not show any effects on the survival of the host animals. Histological examination of the GM-CSF-producing tumor revealed predominant infiltration of neutrophils and necrotic change of the tumor. The present study indicates the feasibility of cancer gene therapy with the expression of GM-CSF gene in tumor cells.
Animals↗
Murine colon carcinoma cells engineered to produce human interleukin-2 induce tumor-specific anti-tumor response.
Murine colon carcinoma cells (colon 26) transduced by a retrovirus vector with the human interleukin-2 (IL-2) cDNA were studied for their tumorigenicity. Although cell growth in vitro was not affected by integration of the IL-2 gene, s.c. tumors of IL-2-producing colon 26 cells (H2) in syngeneic mice regressed spontaneously after producing small masses. Histological examination of the sites of tumor rejection revealed predominant infiltration of macrophages around the tumor necrotic mass. Subsequent challenge with parent colon 26 cells, but not with Meth A cells (fibrosarcoma of the same genetic background), did not result in tumor formation in mice which had been protected against H2 cells. Inoculation of H2 cells into syngeneic nude mice resulted in tumors with a retarded growth rate. Taken together, T cell-dependent, tumor-specific immunity is obtained by local IL-2 secretion around colon tumors, and this experimental animal model gives us a clue(s) for investigating host anti-tumor responses by cytokine production.
Animals↗