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T Osaki

Publications and source records attributed to T Osaki.

At least 145 records · Page 8Linked to original sources
PubMed1996

Suppression by anticancer agents of reactive oxygen generation from polymorphonuclear leukocytes.

The influence of anticancer agents on signal transduction for reactive oxygen generation was examined in polymorphonuclear leukocytes (PMN). Inositol 1,4,5-trisphosphate and diacyl glycerol levels in formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMN were decreased by cis-diammine-dichloroplatinum (CDDP), 5-fluorouracil (5-FU), 137Cs, and peplomycin (PLM, a bleomycin analog) in this order. Intracellular calcium ([Ca2+]i) level and protein kinase C (PKC) activity in the membrane after phorbol myristate acetate (PMA) stimulation were decreased by 5-FU and CDDP but not by 137Cs and, in contrast, were increased by PLM. The level of [Ca2+]i was decreased by 8 h treatment with 5-FU and CDDP. 5-FU and CDDP inhibited tyrosine phosphorylation of 83-kDa and 115-kDa proteins, however 137Cs did not inhibit their phosphorylation and PLM enhanced the tyrosine phosphorylation. Short term (< or = 4 h) treatment with PLM, 5-FU and CDDP enhanced respiratory burst of PMN, whereas long term (8 h) treatment, as well as radiation, suppressed reactive oxygen generation from PMN in a dose dependent manner. Genistein suppressed chemiluminescence in 5-FU-, CDDP-, and 137Cs-pretreated PMN to a greater extent than it did in PLM-pretreated PMN, however near suppression of chemiluminescence by staurosporine, 4-bromophenyl bromide and methionine was observed in PMN pretreated with these agents. In conclusion, these results indicate that long term treatment of PMN with 5-FU and CDDP inhibit respiratory burst, suppressing intracellular calcium mobilization, PKC translocation and tyrosine kinase activation, in adverse, short term treatment with PLM enhances PKC translocation and tyrosine kinase activation, but inhibits myeloperoxidase (MPO) activity, and radiation causes weak inhibition of signal transduction for respiratory burst.

Antineoplastic Agents↗
PubMed1996

Induction and epitope analysis of Helicobacter pylori heat shock protein.

Induction of heat shock proteins (HSPs) was analyzed in Helicobacter pylori strains. With heat shock at 42 degrees C, a synthesized 60 kDa-HSP (HSP60) was detected on autoradiography. The expression of HSP60 on the cell surface of H. pylori was examined by flow cytometric analysis. All strains used in this study expressed HSP60 on the cell surface, although the intensity differed among the strains, depending on culture conditions. The reactivity of a monoclonal antibody (mAb), 3C8, directed against bacterial HSP60, with HSP60 derived from ten strains of H. pylori and with human gastric carcinoma cell HSP60 was examined by immunoblot analysis. An epitope that reacted with the mAb was detected in the HSP60 of H. pylori and on the surface of human gastric carcinoma cells.

Antibodies, Monoclonal↗
PubMed1996

Loss of heterozygosity at 3p in non-small cell lung cancer and its prognostic implication.

We examined 110 patients with non-small cell lung cancer who underwent consecutive pulmonary resection for loss of heterozygosity (LOH) at the short arm of chromosome 3 (3p). We performed a PCR-based microsatellite polymorphism analysis for detection of LOH. The microsatellite markers used were D3S966 (3p21.3), D3S1007 (3p21. 3-22), and D3S1228 (3p14.1-14.3). Of 98 informative cases, 3p LOH was found in 45 (46%). 3p LOH was more prevalent in squamous cell carcinoma (24/35, 69%) than in adenocarcinoma (18/52, 35%; P = 0.0019). There was no significant association between 3p LOH and sex, disease stage, or grade of differentiation. However, patients with 3p LOH tended to survive for a shorter period of time (P = 0.0631, log rank test). There was no such tendency in squamous cell carcinoma (P = 0.7513), but in adenocarcinoma, the difference of survival was significant (P = 0.0015). Cox's proportional hazards model also predicted that 3p LOH was an independent poor prognostic marker in adenocarcinoma (P = 0.0502) but not in squamous cell carcinoma or in the entire cohort (P = 0.7866 and 0.1371, respectively). LOH at 3p may help to identify non-small cell lung cancer patients with a poor prognosis, who thus need an intensive postoperative follow-up protocol or who are suitable for novel investigational therapeutic approaches. It is also suggested that the putative tumor suppressor gene at 3p may have a different role in squamous cell carcinoma and adenocarcinoma of the lung.

Adult↗
PubMed1995

Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese.

Isoleucine (Ile)-valine (Val) polymorphism, which is caused by a point mutation from A to G in exon 7, is reported to be associated with an elevated risk of lung cancer among Japanese. Because CYP1A1 catalyzes bioactivation of environmental procarcinogens, such as benzo[a]pyrene, it is very important to study the clinical meaning of Ile-Val polymorphism using an epidemiological study. In an epidemiological study, easy, economical, rapid and reliable identification of the CYP1A1 genotype is necessary. The present study shows that the new method, designed restriction fragment length polymorphism (designed RFLP), can detect Ile-Val polymorphism of CYP1A1. The Ile-Val polymorphism detected using this new method was consistent with that found by the allele-specific PCR amplifications (ASA) method in six cases tested. This new method detected Ile-Val polymorphism of CYP1A1 using 240 healthy Japanese who lived in the northern Kyusyu region. The frequency of the genotypes was as follows: Ile/Ile 159 (66.2%); Ile/Val, 65 (27.1%); Val/Val, 16 (6.7%). The frequency of the Ile gene was 0.798 and that of the Val gene, 0.202. There was no difference in Ile-Val polymorphism based on sex or age. Racial differences influenced the distribution of this polymorphism, but Japanese regional differences did not. Since this new method, designed RFLP, is rapid, reliable and suitable for large-scale screening of polymorphisms, it may be used routinely to detect Ile-Val polymorphism of CYP1A1. Furthermore, it will help to evaluate the relationship between CYP1A1 polymorphism and individual sensitivity to xenobiotics that may affect the incidence of lung cancer.

Adult↗
PubMed1995

Contrasting influence of peplomycin and azelastine hydrochloride (Azeptin) on reactive oxygen generation in polymorphonuclear leukocytes, cytokine generation in lymphocytes, and collagen synthesis in fibroblasts.

The influence of peplomycin (PLM) and azelastine hydrochloride (Azeptin) on reactive oxygen (RO) and cytokine generation was examined in human peripheral blood mononuclear leukocytes, polymorphonuclear leukocytes (PMN), and rabbit alveolar macrophages (RAM). In addition, the influence of these drugs on DNA and collagen synthesis was investigated in human gingival and rabbit pulmonary fibroblasts. In vitro, PLM increased the FMLP- and PMA-induced chemiluminescence and superoxide (O2-) generation in human PMN and RAM in a dose-dependent manner. In contrast to PLM, Azeptin dose-dependently suppressed RO generation. Such contrasting actions of PLM and Azeptin were also observed in RAM and PMN obtained from rabbits treated with PLM or Azeptin. Even when human PMN were preincubated with 10-100 micrograms/ml of PLM, the increase in RO generation was negligible in the presence of 10(-5) M Azeptin in the culture medium. No increases in RO generation were observed in RAM or PMN obtained from rabbits that had received PLM (0.1 mg/kg per day) and Azeptin (0.04 mg/kg per day) concomitantly. PLM suppressed superoxide dismutase activity in RAM and human PMN, while Azeptin did not affect this activity. In vitro, PLM up-regulated the release of interleukin-1 beta, interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor both from human cells and from RAM and pulmonary fibroblasts. In the generation of these cytokines, Azeptin abrogated the up-regulatory action of PLM. PLM and Azeptin also had contrasting actions in [3H]thymidine and [3H]proline incorporation in human and rabbit fibroblasts. Furthermore, protein tyrosine phosphorylation, in particular that of a 115-kDa protein in human PMN, was suppressed by Azeptin and enhanced by PLM. These results seem to indicate that up-regulated RO and collagen generation are the causative factors of PLM-induced pulmonary fibrosis and that Azeptin may suppress the adverse effect.

Animals↗
PubMed1995

Influence of aging and chemoradiotherapy on leucocyte function in oral cancer patients.

Leucocyte functions and the influence of chemoradiotherapy were examined in three age groups of patients with oral cancer. The groups consisted of 66 patients below 65 years old (group A): 40 patients between 65 and 80 years old (group B); 20 patients over 80 years old (group C). 20 healthy individuals (45.8 +/- 9.6 years old) were chosen as controls. Originally, no significant differences in leucocyte count, CD3 population, CD4/CD8 ratio, natural killer activity or phagocytosis of polymorphonuclear leucocytes (PMNL) were found in the patients. However, T cell blastogenesis, lymphokine-activated killer cell activity and superoxide production of PMNL were all suppressed. These functions were further suppressed by cancer therapy, the greatest suppression being seen in group C. Compared to controls and group A, the generation of interleukin-1, interleukin-6, tumour necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor were markedly suppressed in group C. These results show that very old cancer patients are already in an immunologically suppressed condition and that the leucocyte functions of these patients are further impaired by cancer therapy.

Adult↗
PubMed1995

An immunohistochemical study of odontogenic mixed tumours.

Five cases of odontogenic mixed tumour comprising of an ameloblastic fibroma, an adenomatoid odontogenic tumour, an odonto-ameloblastoma and two ameloblastic fibro-odontomas were immunohistochemically investigated. Odontogenic epithelial cells were fully positive for cytokeratin detected by antibody KL-1, although there were some differences in its intensity. In contrast, for tenascin, only immature dental papilla-like mesenchymal tissue, especially around the dental lamina-like odontogenic epithelium, was positive, while the myxomatous area and connective tissue were negative. Positive vimentin staining was observed in some areas of immature dental papilla-like cells as well as the basement membrane of odontogenic epithelium in the ameloblastic fibroma, suggesting that this tumour had developed at the early stage of tooth formation. Proliferating nuclear cell antigen-positive cells were generally rarely seen, but were frequently observed in epithelial cells of the ameloblastic fibroma and odonto-ameloblastoma. These observations suggest that tumour cells in each odontogenic mixed tumour possess characteristic proteins associated with proliferation potential and that ameloblastic fibroma and odonto-ameloblastoma have higher proliferation potential among the tumours examined.

Adolescent↗
PubMed1995

Proliferating cell nuclear antigen may be superior to argyrophilic nucleolar organizer regions in predicting shortened survival of patients with non-small cell lung cancer.

We examined proliferating cell nuclear antigen (PCNA) in 102 patients with surgically treated non-small cell lung cancer (NSCLC). PCNA labelling index (LI) tended to be higher in tumours of higher stages than those of early stages, in squamous cell carcinomas than adenocarcinomas, or in poorly differentiated adenocarcinoma than in well-differentiated. A positive correlation was observed between the PCNA LI and argyrophilic nucleolar organizer regions (Ag-NOR) count which we previously examined (r = 0.31, P = 0.002). In survival analysis of 79 patients who died of lung cancer, only age, stage and PCNA LI were found to be significant prognostic factors on multivariate analysis among seven potential prognostic factors including sex, age, year of operation, histological type, stage, Ag-NOR count, and PCNA LI. We conclude that PCNA may be superior to Ag-NOR in predicting shortened survival of patients with non-small cell lung cancer. PCNA staining can be performed with ease and it may be applied in a clinical laboratory on a routine basis to help predict prognosis of NSCLC.

Adult↗
PubMed1995

Infections in elderly patients associated with impacted third molars.

The objective of this study was to determine the clinical characteristics of infections caused by impacted third molars in elderly persons. Infectious disorders (26 pericoronitis, 8 secondarily infected dentigerous cysts, 4 perimandibular abscesses with limited osteomyelitis, 2 chronic mandibular osteomyelitis, and 1 odontogenic skin fistula) associated with the impacted third molars impacted third molars were clinically investigated in 41 patients over 60 years of age. Twenty-nine causative teeth were located in the mandibular angle and nine in the ramus; the three remaining lesions (two cysts one pericoronitis) were associated with the maxillary third molar. Bone resorption was noted in most patients, and this caused the originally embedded tooth to become exposed intraorally. It was concluded that oral infection in elder persons are occasionally caused by retained impacted third molars with overlapping of other factors.

Age Factors↗
PubMed1995

p53 nuclear immunostaining and gene mutations in non-small-cell lung cancer and their effects on patient survival.

BACKGROUND: p53 gene mutations are known to occur in about half of all non-small-cell lung cancer (NSCLC) cases. Mutations of the p53 gene usually but not always lead to an increased half life of the p53 protein, and result in a nuclear accumulation of protein which can be detected by immunohistochemistry (IHC). Controversy still exists as to whether the presence of an aberration of the p53 gene or protein is a poor prognostic indicator in patients with NSCLC. PATIENTS AND METHODS: DNA samples and paraffin blocks were obtained from 129 patients of 143 consecutive patients who underwent a pulmonary resection during a 22-month period from July 1991 to April 1993. Mutations of the p53 gene occurring at exons 5-8 were detected by a polymerase chain reaction (PCR)/single strand conformation polymorphism (SSCP) assay, while the nuclear accumulation of the p53 protein was detected by immunohistochemistry. RESULTS: Of the patients studied, 35% had mutations and 54% showed overexpression, when we defined a positive case as being one in which more than 10% of the tumor cell nuclei were stained. There was a 59.5% concordance between the p53 gene mutations and p53 immunopositivity. p53 immunopositivity in adenocarcinoma and any p53 abnormality (i.e. p53 immunopositivity and/or mutation) in adenocarcinoma were a poor prognostic indicator. However, Cox's proportional hazards model indicated that the stage was the only significant prognostic factor. CONCLUSIONS: p53 immunopositivity and mutations of the p53 gene are frequently seen in NSCLC. They are considered to be mutually related but may sometimes represent a different aspect of p53 abnormality. p53 alteration may be a poor prognostic indicator only in a subset of patients with NSCLC, especially for adenocarcinoma.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Characteristic cytokines generated by keratinocytes and mononuclear infiltrates in oral lichen planus.

Cytokine production was investigated in oral keratinocytes and tissue-infiltrated mononuclear cells (TIMC) obtained from patients with oral lichen planus (OLP). The numbers of cells producing interleukin (IL)-1 beta, IL-4, IL-6, granulocyte colony-stimulating factor, and tumor necrosis factor-alpha per 10(4) cells in keratinocytes from patients with OLP were determined by enzyme-linked immunospot assay. These levels were two to threefold greater than those in keratinocytes from chronically inflamed gingiva and 10 to 20-fold of those from the intact gingiva. The concentrations of these cytokines in the culture supernatants of keratinocytes were correlated with the number of cytokine-producing cells. Compared with TIMC in the gingiva and peripheral blood mononuclear cells, TIMC in OLP were more cytokine-productive, with larger numbers of cytokine-producing cells that expressed more cytokine messengers. More IL-6, IL-2, and IL-10 were generated from TIMC in OLP, whereas less granulocyte colony-stimulating factor was generated. After pretreatment with IL-2, TIMC from OLP patients generated more IL-6 than did peripheral blood mononuclear cells, and IL-4-pretreated TIMC from the patients released larger amounts of IL-2, IL-6, and IL-10. These results indicate that keratinocytes play a critical role in OLP through production of large amounts of cytokines, that TIMC are stimulated in situ and differentiated to produce cytokines characteristic of OLP, and that the inflammatory condition of OLP is determined by the local cytokine network.

Cytokines↗
PubMed1995

Flow cytometric analysis using lipophilic dye PKH-2 for adhesion of Vibrio cholerae to Intestine 407 cells.

A comparative study of indirect and direct flow cytometric analysis for adherence of Vibrio cholerae to Intestine 407 cells was performed. The direct flow cytometric analysis employed the lipophilic dye PKH-2. It was concluded that direct flow cytometry using the lipophilic dye PKH-2 is useful and convenient for analyzing bacterium-host cell interactions, since it does not require any specific antibody as the first antibody.

Bacterial Adhesion↗
PubMed1995

Longer local retention of adoptively transferred T-LAK cells correlates with lesser adhesion molecule expression than NK-LAK cells.

The local retention of adoptively transferred lymphokine (IL-2)-activated killer (LAK) cells was examined in 11 patients with head and neck carcinoma. Unseparated lymphocytes, T and natural killer (NK) cells isolated from patients were cultured with IL-2 for 7 days, labelled with 99mTc-HMPAO, and immediately injected back into the respective donors via the superficial temporal artery or locally into the tumour tissue. The injected LAK cells were periodically traced using a gamma camera, and the LAK cell retention rate was calculated from the radioactivity. One hour after the injection, about 70% of the locally infiltrated LAK cells remained in the tumour tissue, while about half of the LAK cells transferred via the regional artery were dislodged from the tissue. LAK cells induced from T cells (T-LAK) were retained in the tissue for a longer time than LAK cells induced from NK cells (NK-LAK). T-LAK were less chemotactic and less adherent to human umbilical vein endothelial cells (EC), and showed lesser migration through EC. Flow cytometric analysis revealed higher expression of CD11a, CD11b, CD18 and CD49d on NK-LAK compared with T-LAK. MoAbs against these adhesion molecules suppressed adhesion and migration of LAK cells. These results indicate that the rapid disappearance of NK-LAK from the tissue is associated with their greater chemotactic and adhesive as well as migratory activities depending on differing expression of adhesion molecules.

Adult↗
PubMed1995

Reduced inhibition of Candida albicans adhesion by saliva from patients receiving oral cancer therapy.

The effect of saliva on the adhesion of Candida albicans to epithelial cells was examined in vitro by using saliva from healthy controls and patients with oral squamous cell carcinoma. The adhesion of C. albicans to established epithelial tumor cells was reduced by 40% by salivary treatment of the C. albicans or epithelial cells. The inhibitory activity of saliva was almost completely abolished by anti-secretory immunoglobulin A antibody, concanavalin A, and mannose. Compared with saliva from healthy individuals, that from patients who had received chemoradiotherapy for oral carcinoma showed reduced suppression of C. albicans adhesion, which accompanied decreased salivary secretory immunoglobulin A and lactoferrin concentrations. A greater number of C. albicans cells adhered to buccal cells obtained from patients who had received chemoradiotherapy than to those from healthy individuals. Treatment of either epithelial cells or C. albicans with anticancer drugs induced an increase in adherence of epithelial cells and yeast cells. In contrast, concanavalin A- and mannose-pretreated C. albicans exhibited reduced adhesion to epithelial cells. No further decrease of C. albicans adhesion was observed when both epithelial cells and yeast phase C. albicans were treated with mannose. In conclusion, the inhibition of C. albicans adhesion by saliva depends largely on mannose residues on salivary glycoproteins and mannose is one of the binding ligands on both C. albicans and epithelial cells. In addition, anticancer therapy may induce oral C. albicans overgrowth by decreasing salivation and the concentrations of glycoproteins in saliva inhibiting C. albicans adhesion and by increasing the adhesive properties of both C. albicans and oral epithelial cells.

Administration, Oral↗
PubMed1995

Enhanced cytokine production and collagen synthesis of gingival fibroblasts from patients with denture fibromatosis.

The mechanisms of denture-induced gingival hypertrophy remain to be explored. Since fibroblast proliferation and bone resorption characterize this disorder, the possible involvement of cytokines was investigated. Gingival fibroblasts were obtained from six patients with denture fibromatosis (Den-Fb) and six healthy persons (Nor-Fb). Cells were compared for proliferation, collagen synthesis, and cytokine production. Incorporation of [3H]thymidine (TdR) was increased in 3 Den-Fb and 3 Nor-Fb lines in the presence of interleukin-1-beta (IL-1 beta) (10 U/mL) and tumor necrosis factor-alpha (TNF-alpha) (from 10 to 100 U/mL). Proline incorporation in Den-Fb was higher than that in Nor-Fb, and the mean collagen synthesis level in Den-Fb was significantly higher than that in Nor-Fb. Although there was no difference between the up-regulation of protein synthesis in Den-Fb and Nor-Fb induced by IL-1 beta or TNF-alpha, the receptors for these cytokines were expressed at higher levels in cell lines which exhibited higher protein synthesis. Between Nor-Fb and Den-Fb, there was no difference in the generation of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-6 (IL-6). However, most Den-Fb produced more GM-CSF and IL-6 in the presence of TNF-alpha. Enhancement of IL-6 generation by GM-CSF was also more prominent in Den-Fb. GM-CSF and IL-6 were synergistically generated after co-culture of the fibroblasts with gingival keratinocytes. GM-CSF and IL-6 generation of Den-Fb was markedly enhanced by co-culture of Den-Fb with peripheral blood mononuclear cells (PBMC), especially PBMC from patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Serum level and tissue expression of c-erbB-2 protein in lung adenocarcinoma.

Serum levels of c-erbB-2 protein were measured by an enzyme immunoassay in 64 patients with lung adenocarcinoma. Immunohistochemical staining was performed in 40 of these tumors. The mean serum concentration was 16.5 +/- 8.5 U/mL (range: 3.4 to 49.0) in patients with lung adenocarcinoma, whereas it was 14.0 +/- 3.7 U/mL (range: 6.9 to 20.9) in 15 controls (1 U/mL = 0.61 ng/mL). Elevated concentrations (> or = 22.0 U/mL, control mean + 2 SD) were observed in 17/64 lung adenocarcinoma patients (26.6%), as compared with none of the control subjects (p < 0.05). Patients with stage IIIB or T4 disease had increased serum levels. The serum concentration was decreased significantly by surgical tumor ablation. Tissue overexpression was obtained in 17/40 cases (42.5%), and serum levels in patients with tissue overexpression were higher than in patients without overexpression. Serum c-erbB-2 protein may be a useful indicator of tumor burden in patients with lung adenocarcinoma.

Adenocarcinoma↗