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Biomedical subjects

T Osaki

Publications and source records attributed to T Osaki.

At least 163 records · Page 9Linked to original sources
PubMed1995

Upregulation of respiratory burst of polymorphonuclear leukocytes by a bleomycin derivative, peplomycin.

The influence of peplomycin (PLM) on the respiratory burst of peripheral blood polymorphonuclear leukocytes (PMN) was investigated. Short-term (5 min) treatment of human PMN with 0.1mu g/ml to 100mu g/ml of PLM increased phorbol myristate acetate (PMA)- and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced luminol-dependent chemiluminescence. PMN, as well as alveolar macrophages from rabbits treated with 0.5 to 1.0 mg/kg of peplomycin per day for 5 days, generated more superoxide (O2-) than the cells from untreated rabbits. In both PLM-treated and untreated PMN, chemiluminescence induced by FMLP and PMA was decreased to less than 50% of the control by staurosporine, superoxide dismutase (SOD) and catalase. However, the peak intensity in PLM-untreated PMN was decreased to about 30% of the control by genistein, while this agent induced a slight decrease in peak intensity in the PLM-treated PMN. Inositol triphosphate and diacyl glycerol levels were not clearly increased by PLM, but an increase of intracellular Ca++ and a shift of protein kinase C (PKC) to the membrane occurred in PMN within 1 min after PLM treatment. Western blotting revealed that the tyrosine phosphorylation of a 115 kDa protein was upregulated by 5 to 50mu g/ml of PLM. While, PLM suppressed SOD activity in alveolar macrophages and PMN. These results seem to indicate that PLM increases the respiratory burst of PMN and macrophages both by way of direct PKC activation and by the upregulation of protein tyrosine phosphorylation. This increased reactive oxygen generation, together with the suppression of SOD activity seems to be tissue-impairing.

Humans↗
PubMed1994

Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene.

A carcinoembryonic antigen (CEA)-producing human lung cancer cell line (A549), a nonproducing human lung cancer cell line (CADO-LC9), and a human uterine cervical cancer (HeLa) were transfected with the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by 445 nucleotides upstream from the translational start of CEA gene. Fifty % growth inhibitory concentration of ganciclovir (GCV) was 0.57 micron for HSV-TK-transfected A549; relative sensitivity to GCV was more than 1000 times higher compared to the 50% growth inhibitory concentration of the parental cell line. Both CADO-LC9 and HeLa transfected with HSV-TK were still resistant to GCV. There was no difference in either morphology or doubling time between HSV-TK-transfected and parental clones. Injections (i.p.) of GCV resulted in significant regression of HSV-TK-transfected A549 tumors in nude mice. These data show the possibility of gene therapy using the cell type-specific promoter of CEA gene against CEA-producing adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1994

A frequent deletion of chromosome 5q21 in advanced small cell and non-small cell carcinoma of the lung.

We have examined the deletion of the long arm of chromosome 5 (5q) in 59 cases of advanced lung cancer [39 cases of small cell lung cancer (SCLC), 20 cases of non-SCLC] using 12 restriction fragment length polymorphism markers on 5q. Of 59 lung cancer cases, 48 (81%) exhibited deletion at any portion of the 5q locus (loci). Such a high frequency of 5q deletion has not been reported in surgically resectable non-SCLC. One SCLC case showed a 5q deletion only in metastatic sites but not in the primary cancer. These data suggest that the inactivation of putative tumor-suppressor gene(s) on 5q may be a late event in the progression of lung cancer. There was no significant difference in frequency of 5q deletion between SCLC and non-SCLC. Compared to non-SCLC, however, SCLC usually showed widespread deletion on 5q. While the most frequent target region was estimated to be about 3-5 megabases at 5q21 around the adenomatous polyposis coli (APC) gene locus, some cases showed more telomeric deletion (5q33-35), suggesting that there are at least two different tumor-suppressor genes on 5q associated with the progression of lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Naive T cells can mediate delayed-type hypersensitivity response in T cell receptor transgenic mice.

We produced transgenic mice expressing T cell receptor-alpha beta chain genes, derived from the chicken ovalbumin (OVA)-specific I-Ad-restricted CD4+CD8- T helper cell clone 7-3-7. In transgenic mice with H-2d genetic background (Tg-d mice), delayed-type hypersensitivity (DTH) was induced in the hind footpad by one inoculation with OVA without any previous sensitization, suggesting that naive T cells have the potential to be involved in DTH response. Spleen cells from nonimmunized Tg-d mice showed a strong T cell proliferative response to in vitro stimulation with OVA. Furthermore, these spleen cells produce cytokines including interleukin(IL)-2, IL-3, interferon-gamma, granulocyte/macrophage colony-stimulating factor, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta, which may play an important role in the attraction of mononuclear cells to an antigen-challenging site.

Animals↗
PubMed1994

Suppression of respiratory burst of polymorphonuclear leukocytes by azelastine hydrochloride (Azeptin).

The inhibitory action of azelastine hydrochloride (Azeptin) on the respiratory burst in peripheral polymorphonuclear leukocytes (PMN) and pulmonary alveolar macrophages (PAM) has been studied. Azeptin in vitro suppressed chemiluminescence and superoxide (O2-) generation by human PMN in a dose- and time-dependent manner. Phorbol myristyl acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O2- generation were strongly suppressed by 10(-6) M and 10(-5) M Azeptin, respectively. PMN and PAM from rabbits injected with Azeptin 0.2 mg.kg-1 for 5 days showed lower chemiluminescence and O2- generation than cells from untreated rabbits. Nitroblue tetrazolium reduction activity in human PMN was suppressed by treatment of PMN with 10(-6) M Azeptin for 6 h. Inositol trisphosphate, intracellular free calcium, and protein kinase C activity were decreased by 10(-6) M to 10(-5) M Azeptin. The tyrosine phosphorylation of many proteins, especially a 115 kDa protein, was suppressed by 10(-5) M Azeptin. However, superoxide dismutase activity in PMN, PAM, and lung tissue samples was only slightly decreased, even when the rabbits were treated with 1.0 mg.kg-1 Azeptin for 5 days. The results suggest that Azeptin suppresses multiple signal transduction steps in the respiratory burst of PMN. This suppressive action should be very useful in the prevention and treatment of reactive oxygen-associated disorders.

Animals↗
PubMed1994

Surgical treatment of lung cancer in the octogenarian.

The purpose of this study was to investigate the value of surgical treatment for lung cancer in the octogenarian. Thirty-three patients 80 years of age or older (mean age, 82.4; range, 80 to 92 years; 25 men, 8 women) underwent surgical resection in our units between 1974 and 1991. The operative mortality rate was 3%, and the 5-year survival rate was 32%. The relative 5-year survival rate (survival rate of our subjects/that of matched population) was 61%. The mortality and long-term survival rates were similar to those in younger patients. In this study, long-term survival had no significant dependence on stage of disease, histologic tumor type, or complete versus incomplete resection. It was dependent mainly on postoperative complications, in particular, cardiorespiratory complications (cardiac complications, p = 0.0005; respiratory complications, p < 0.05). These data suggest that the octogenarian who suffers from lung cancer deserves the opportunity for a cure and the long-term benefits of surgical treatment, on the condition that no postoperative major cardiorespiratory complications set in.

Aged↗
PubMed1994

Serum cytokines, interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in oral disorders.

Serum levels of soluble intercellular adhesion molecule-1, soluble interleukin-2 receptor, and cytokines such as interleukin-3, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were examined in patients with oral disorders with 20 healthy persons used as control subjects. Patients studied included 30 with squamous cell carcinoma, 26 with oral lichen planus, 20 with recurrent aphthous ulcer, 19 with acute odontogenic bacterial infection, 16 with pseudomembranous candidiasis, and 16 with herpetic gingivostomatitis. Compared with levels in control subjects, detectable serum levels of interleukin-3 (> or = 10 pg/ml) existed more frequently in pseudomembranous candidiasis (13/16), acute odontogenic bacterial infection (14/19), and squamous cell carcinoma (24/30) and of granulocyte-macrophage colony-stimulating factor (> or = 4 pg/ml) more frequently in recurrent aphthous ulcer (15/20) and squamous cell carcinoma (21/30). These cytokine levels were increased with T stage of squamous cell carcinoma. About 20 pg/ml of interleukin-4 was detected in serum from one third to one fourth of patients with oral lichen planus, recurrent aphthous ulcer, and squamous cell carcinoma. Tumor necrosis factor-alpha was hardly detected in most patients except those with oral lichen planus and squamous cell carcinoma in which about one third of the patients had more than 40 pg/ml of tumor necrosis factor-alpha in serum. More than 10 pg/ml of interleukin-6 was frequently detected in all disorders, especially recurrent aphthous ulcer (18/20), pseudomembranous candidiasis (12/16), and acute odontogenic bacterial infection (17/19).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Detailed deletion mapping of the short arm of chromosome 3 in small cell and non-small cell carcinoma of the lung.

We constructed a detailed deletion map of the short arm of chromosome 3 (3p) for 55 lung cancer cases by using 17 restriction fragment length polymorphism (RFLP) probes. Initially, we examined 40 small cell lung cancer (SCLC) cases and found three regions of deletion at 3p25-26, 3p21.3 and 3p14-cen, suggesting the possibility of at least three different tumor-suppressor genes on 3p. In order to obtain more detailed deletion area, and to compare the pattern of 3p deletion, we also examined 15 non-small cell lung cancer (NSCLC) cases. Compared to NSCLC cases, most of SCLC cases have widespread deletion on 3p, suggesting multiple tumor-suppressor genes on 3p may be inactivated in this type of cancer. In 3p21.3 area, minimum overlapping area of deletion lays between two probes which are close to each other. These data will be useful to isolate the putative tumor-suppressor genes located on the chromosome 3p.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Enhancement of polymorphonuclear leukocyte (PMN) function by OK-432.

The influence of OK-432, a streptococcal preparation, on human polymorphonuclear leukocytes (PMN) was examined. OK-432 increased O2- generation was also observed when PMN were cultured with 10(-2)KE/ml OK-432 for 1 h and then stimulated with phorbol myristate acetate or formyl-metionyl-leucil-phenylalanine (FMLP). In addition, PMN O2- generation was promoted by culture supernatants of peripheral blood mononuclear cells (PBMC) incubated with 10(-3) or 10(-2) KE/ml OK-432. Furthermore, OK-432 (10(-3)-10(-2) KE/ml) enhanced the chemiluminescence of FMLP- and PMA-stimulated PMN. However, nitroblue tetrazolium reduction and myeloperoxidase activity were only minimally enhanced. Not only the candidacidal activity of PMN but also antibody-dependent cell-mediated cytotoxicity against Candida and Raji cells were enhanced in correspondence with the increased generation of reactive oxygen species. Culture of PMN or PBMC for 24 h with OK-432 resulted in a concentration-dependent increase in the substantial production of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha. OK-432 also enhanced granulocyte-macrophage colony stimulating factor and gamma-interferon generation by leukocytes in a dose-dependent manner. Our research indicates that OK-432 enhances PMN function directly as well as via the promotion of cytokine production, and suggests that these effects of OK-432 could be beneficial in immunosuppressed patients.

Candida albicans↗
PubMed1994

Tumorigenicity of cell lines established from oral squamous cell carcinoma and its metastatic lymph nodes.

We investigated the biological and histopathological characteristics of seven human tumour cell lines established from primary tongue squamous cell carcinoma (OSC-1), from metastasised lymph nodes of the gingival carcinoma (OSC-2 and OSC-3) and from tongue carcinoma (remaining four lines). The doubling time ranged from 22 h (OSC-2 and OSC-4) to 55 h (OSC-7), and did not correlate with tumour cell stratification in a collagen gel matrix. An invasive tendency was most prominent in OSC-2 and OSC-4; with the other cell lines, except OSC-6 and OSC-7, only a few sporadic invading cells were found in the tissue culture. In the cell lines established from the metastatised tumours, originally exhibiting grade 3 invasion, the invasion became more sporadic when the tumour cells were xenografted into the tongues of nude mice, while an invasion similar to the original was observed in the cell lines obtained from the original site (OSC-1) and from tumours of Grade 4C invasion. These findings suggest that the biological behaviour of the established tumour cells is markedly different even in tumours of the same tissue origin, and strongly invasive cells may selectively invade, and metastatise to the lymph nodes.

Aged↗
PubMed1994

NK-LAK induction with IL-2 is regulated by tyrosine phosphorylation of a 105-110 kDa protein.

Tyrosine phosphorylation of the cellular proteins of IL-2-stimulated NK cells was determined by anti-phosphotyrosine immunoblotting. IL-2 induced tyrosine phosphorylation of a 105-110 kDa protein in a dose-dependent manner. The tyrosine phosphorylation took place within 5 min after the addition of IL-2 to NK cells, and reached a maximal level in 15 min. The degree of the tyrosine phosphorylation correlated with IL-2-induced LAK activity. Staurosporine and pertussis toxin, which slightly suppressed LAK induction, did not inhibit tyrosine phosphorylation of the 105-110 kDa protein. Genistein, TMB-8 and EGTA completely inhibited LAK induction; however, the calcium channel blocker and chelator did not prevent the protein tyrosine phosphorylation. Anti-IL-2R beta mAb almost completely suppressed tyrosine phosphorylation of the 105-110 kDa protein, but anti-IL-2R alpha mAb only slightly suppressed it; this result correlated with that of the suppression of LAK activity. No further suppression of the tyrosine phosphorylation was induced even when both mAbs were added. Western blotting of the immunoprecipitates revealed no association of PLC-gamma 1 or IL-2R beta with the 105-110 kDa protein. These results suggest that both tyrosine phosphorylation of the 105-110 kDa protein and translocation of [Ca++]i are essential for NK-LAK induction, and the tyrosine phosphorylation plays a critical role in the early stage of IL-2 signalling from the IL-2R beta chain.

Blotting, Western↗
PubMed1994

Cytokine production by keratinocytes and mononuclear infiltrates in oral lichen planus.

Cytokine generation by tissue-infiltrating mononuclear cells (TIMC) and by keratinocytes (KC) was investigated in material obtained from the oral mucosal tissues of patients with oral lichen planus (OLP). Peripheral blood mononuclear cells (PBMC) and chronically inflamed and noninflamed gingival KC (CIG-KC, NOR-KC, respectively) were used as the controls. Compared to NOR-KC and CIG-KC, KC from OLP patients (OLP-KC) produced much more interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The OLP-KC superiority in the production of these cytokines was more prominent when the KC were cultured in the presence of interleukin-1 beta (IL-1 beta), lipopolysaccharide and phorbol myristate acetate. OLP-KC also produced more monocyte-chemotactic factor(s) which were not inactivated by the antibodies against GM-CSF, macrophage colony-stimulating factor and monocyte chemoattractant protein-1. TIMC in OLP tissues (OLP-TIMC) were superior to PBMC in the generation of IL-6 and GM-CSF. OLP-TIMC were stimulated to produce more TNF-alpha by IL-1 beta, IL-6 and GM-CSF, more IL-6 by IL-1 beta and GM-CSF, and more GM-CSF by IL-1 beta and IL-6 than PBMC. When compared to cytokine generation in TIMC from the chronically inflamed gingivae, more interferon-gamma, IL-6 and TNF-alpha were generated by OLP-TIMC. These results indicate that KC play a critical role in OLP, producing cytokines including monocyte-chemotactic factor(s), and that the cytokines produced by TIMC and OLP-KC through autocrine and paracrine processes enhance the local inflammatory response.

Adult↗
PubMed1994

Influence of inductive chemoradiotherapy on salivary polymorphonuclear leukocyte (SPMN) functions in oral cancer.

Salivary polymorphonuclear leukocyte (SPMN) functions were examined in 18 patients with oral squamous cell carcinoma and in 20 healthy individuals. SPMN obtained from patients before therapy exhibited significantly less FMLP-stimulated chemotactic activity (132.4 +/- 17.5 cells/0.26 mm2) than that in SPMN from controls (177.1 +/- 11.6 cells/0.26 mm2), although no difference in phagocytosis was observed. When stimulated with PMA or FMLP, control SPMN generated superoxide (O2-) at levels of 50.3 +/- 10.5 pmol/min/10(4) cells and 88.4 +/- 15.4 pmol, respectively, while SPMN from untreated patients generated significantly reduced O2- in the presence of PMA or FMLP (24.3 +/- 3.5 pmol and 59.5 +/- 9.8 pmol, respectively). Only slightly lower chemiluminescence was observed in SPMN from untreated patients however, compared to controls, values being 68.0 +/- 18.9 vs 81.3 +/- 14.9 peak mV by PMA and 62.4 +/- 13.7 vs 64.4 +/- 12.9 peak mV by FMLP. Compared to Candida killing in control subjects (24.9 +/- 3.1%). SPMN from patients before treatment exhibited significantly reduced activity (18.7 +/- 4.9%). Further suppression of the SPMN functions examined was observed after chemoradio-therapy. Suppressed SPMN function in cancer patients, especially that associated with chemoradiotherapy, may therefore play a part in oral candidiasis.

Adult↗
PubMed1994

A clinical trial of Azelastine in recurrent aphthous ulceration, with an analysis of its actions on leukocytes.

Azelastine (azelastine hydrochloride) was orally administered to 43 patients with recurrent aphthous ulcers (RAU), and its clinical effects and in vitro influence on leukocytes were examined. During at least 6 months after drug treatment, no oral ulcers occurred in 7 patients, and an improvement of the oral condition was exhibited in all except 4 of the remaining patients. The frequency of occurrence of RAU was significantly reduced, from 1.7 +/- 0.9 to 0.9 +/- 0.5 times/month, and ulcer duration and oral irritation were also significantly reduced from 12.5 +/- 2.5 and 7.5 +/- 2.4 days to 9.8 +/- 2.6 and 5.3 +/- 2.4 days, respectively. Neutrophils from patients treated with Azelastine generated a suppressed volume of superoxide (O2-). Suppression of O2- generation and chemiluminescence by in vitro Azelastine was also confirmed to occur in a dose-dependent manner. Furthermore, the production of TNF-alpha and GM-CSF in lymphocytes was suppressed in the presence of Azelastine, and the drug protected sheep red blood cells and epithelial tumor cell lines against hydrogen peroxide impairment and hypotonic shock. These clinical and experimental results lead to the conclusion that improvement of RAU by Azelastine depends on the protection of cell membranes and the suppression of leukocyte-function, including reactive oxygen generation.

Adolescent↗
PubMed1994

Combined thoracoscopy and mediastinoscopy for the evaluation of mediastinal lymph node metastasis in left upper lobe lung cancer.

Cervical mediastinoscopy has an important but limited role in the evaluation of mediastinal adenopathy of the aorticopulmonary window in patients with left lung cancer. Thoracoscopy is another valuable diagnostic procedure in the assessment of mediastinal adenopathy. Combined thoracoscopic and mediastinoscopic evaluation may be more accurate for assessing mediastinal lymph node metastasis in left lung cancer than either procedure alone.

Adenocarcinoma↗
PubMed1993

Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer.

BACKGROUND: Inactivation of the p53 tumor suppressor gene (also known as TP53) through a point mutation and/or loss of heterozygosity is one of the most common genetic changes found in various types of human tumors. PURPOSE: Our purpose was to investigate the relationship between the presence of p53 gene mutations and survival of patients with non-small-cell lung cancer (NSCLC) of all stages who underwent surgery with preoperative curative intent as a routine therapeutic intervention. The prognostic significance of factors like sex, age, tumor histology, and the stage of the disease was also evaluated. METHODS: We analyzed 120 tumor specimens from patients with histologically confirmed NSCLC for p53 mutations occurring in exons 5 through 8 by polymerase chain reaction-single-strand conformation polymorphism assay of genomic DNA. Univariate and multivariate analyses were performed to assess the association between p53 mutations and the survival of the NSCLC patients. RESULTS: Fifty-one (43%) of 120 tumor specimens showed p53 mutations. Overall, the p53 mutations did not correlate with sex, age, or the clinical stage of the disease but showed frequent association with tumors of squamous cell histology. Univariate analysis revealed that the patients with p53 mutations survived for a significantly shorter period of time after surgery than those without the mutations (P = .0100, logrank test). The presence of p53 mutations was a significant prognostic factor in the patients with advanced disease (stages IIIA through IV) (P = .0091) but not in those with early disease (stages I and II) (P = .2837). Multivariate analysis using the Cox proportional hazards model found independent prognostic significance for p53 mutations (hazards ratio [HR] = 1.84; P = .018) and advanced disease stage (HR = 2.20; P = .003). The model also predicted the lower risk for female patients (HR = 0.51; P = .040). CONCLUSION: The occurrence of p53 mutations in some NSCLC tumors may be independently associated with a shortened overall survival and may be of somewhat more prognostic significance in patients with advanced stage than in those with early stage of the disease. IMPLICATION: Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.

Aged↗
PubMed1993

Functions of salivary polymorphonuclear leukocytes (SPMNs) and peripheral blood polymorphonuclear leukocytes (PPMNs) from healthy individuals and oral cancer patients.

Functions of salivary polymorphonuclear leukocytes (SPMNs) and peripheral blood polymorphonuclear leukocytes (PPMNs) were synchronously examined in 20 healthy individuals and 13 patients with oral squamous cell carcinoma. In healthy controls, PPMNs generated superoxide (O2-) of 105.2 +/- 19.4 and 105.1 +/- 22.0 pmol/min/10(4) cells under PMA and FMLP stimulation, respectively; SPMNs generated O2- of 50.3 +/- 10.5 pmol with PMA and 88.4 +/- 15.4 pmol with FMLP. Chemiluminescence intensity in SPMNs was 81.3 +/- 14.9 mV with PMA and 62.4 +/- 12.9 mV with FMLP, and chemiluminescence in PPMNs was 229.1 +/- 37.2 and 120.1 +/- 18.4 mV with PMA and FMLP, respectively. Corresponding to the productivity of reactive oxygens, candida killing, and phagocytic activity of SPMNs (24.9 +/- 3.1 and 49.8 +/- 3.6%, respectively) were inferior to those of PPMNs (37.8 +/- 3.8 and 57.5 +/- 3.3%, respectively). Compared with healthy controls, most PPMN and SPMN functions, except for phagocytosis and FMLP-stimulated chemiluminescence, were suppressed in the oral cancer patients. Before treatment, PMA-stimulated O2- generation levels and candidacidal activity were about 70-80% of those in healthy controls. A significant decrease of O2- generation in both PPMNs and SPMNs, as well as a decrease in the candida killing and phagocytic activity of SPMNs were observed following cancer treatment. These results indicate that, while inferior to PPMNs, SPMNs possess adequate candidacidal activity and produce active oxygens. However, both PPMN and SPMN functions are suppressed by the tumor burden, and tumor treatment brings additive neutrophil suppression which may allow fungal infections to develop.

Blood Cells↗