Biomedical subjects

T Osaki

Publications and source records attributed to T Osaki.

At least 37 records · Page 2Linked to original sources

PubMed2001

Generation of autologous tumor-specific T cell clones from a patient with adenosquamous carcinoma of the lung.

BACKGROUND: Adenosquamous carcinoma of the lung is not a common cancer, but its prognosis is worse than that of adenocarcinoma or squamous cell carcinoma. Therefore, new therapeutic strategies need to be developed to treat this type of lung cancer. Recently, vaccination using tumor antigens which are recognized by cytotoxic T lymphocytes (CTL) has been applied mainly to melanoma patients. We therefore attempted to establish T cell clones specific for autologous tumor cells (AT) from a patient with adenosquamous carcinoma in order to analyze the specific immune responses against AT. METHODS: A lung adenosquamous carcinoma cell line was established from a resected tumor obtained from a 72-year-old patient. Regional lymph node lymphocytes were stimulated weekly with CD80-transfected AT to induce CTL. The CTL activities were assessed by a standard (51)Cr release assay and by cytokine release. RESULTS: We succeeded in inducing an AT-specific CTL line. Using a limiting dilution method, eight T cell clones were established. AT-specific activity was observed in three CD8(+) T cell clones and one CD4(+) T cell clone out of the eight clones tested. Anti-HLA class I and anti-HLA-B/C mAbs inhibited IFN-gamma production from the AT-specific CD8(+) clones co-cultured with AT, thus indicating the restriction element to be HLA-B*5201 or HLA-Cw*1202. In contrast, the CD4(+) T cell clone recognized AT in an HLA class II-restricted manner. CONCLUSIONS: These results are the first demonstration of a successful induction of AT-specific T cell clones from a patient with lung adenosquamous carcinoma. It may therefore supply a possible way to apply specific immunotherapy to this type of lung cancer.

Aged↗

PubMed2001

Successful induction of tumor-specific cytotoxic T lymphocytes from patients with non-small cell lung cancer using CD80-transfected autologous tumor cells.

Cytotoxic T lymphocytes (CTL) against human lung cancer cells are difficult to induce by a conventional method using tumor cell stimulation probably due to an insufficiency of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators of the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Five non-small cell lung cancer cell lines (two adenocarcinomas, 1 squamous cell carcinoma, 1 large cell carcinoma and 1 adenosquamous cell carcinoma) were established from surgical specimens and were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA, using a lipofection method. CD80-transfected tumor cells (CD80-AT) significantly augmented the proliferation of autologous lymphocytes from all cases as compared with non-transfected tumor cells (AT). AT-stimulated lymphocytes from 4 out of 5 cases did not show any cytotoxicity against AT; however, lymphocytes stimulated with CD80-AT exhibited substantial cytotoxicity against parental AT in all 5 cases tested. AT-stimulated lymphocytes derived from only one out of 5 cases showed major histocompatibility complex (MHC)-class I-restricted cytokine production in response to AT, while the MHC-class I-restricted responses were found in CD80-AT-stimulated lymphocytes from 4 out of 5 cases. These results indicate that CD80 on tumor cells could be a beneficial costimulatory molecule to elicit CTL against lung cancer, and also show that TA recognized by CTL was frequently expressed on lung cancer cells.

Adenocarcinoma↗

PubMed2001

Peplomycin, a bleomycin derivative, induces myofibroblasts in pulmonary fibrosis.

To analyse the mechanism by which a bleomycin derivative, peplomycin (PLM) induces pulmonary fibrosis, we investigated differentiation of rat pulmonary fibroblasts to myofibroblasts (MF). In intraperitoneally PLM (5 mg/kg/day)-injected rats, the peripheries of lungs adjacent to the pleura revealed advanced fibrosis with a small number of alpha-smooth muscle actin (alpha-SMA)-positive MF, which ultrastructurally possessed abundant microfilaments and cellular organelles. In the fibrotic tissue, the expression of alpha-SMA-mRNA was detected by in situ reverse transcription-polymerase (RT-PCR). The message was strong just after a 2-week administration of PLM then decreased thereafter, although fibrosis advanced. When pulmonary fibroblasts were separated from saline-injected rats (N-Fib) and cultivated for 7 days in the presence of 5 mg/mL PLM, alpha-SMA protein was weakly expressed, while the majority of pulmonary fibroblasts separated from PLM-injected rats (P-Fib) became positive for alpha-SMA in 7-day cultivation and the expression of alpha-SMA in P-Fib was strongly increased by cultivation in the presence of PLM and transforming growth factor-beta (TGF-beta), but not basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF), although the cell proliferation was most strongly enhanced by bFGF and only slightly by PLM and TGF-beta. The alpha-SMA-positive cells expressed vimentin, but only weakly expressed desmin. Additionally, P-Fib generated larger amounts of TGF-beta and bFGF than were generated by N-Fib. These results indicate that PLM induces pulmonary fibrosis by differentiating fibroblasts to alpha-SMA-positive MF, and that bFGF and TGF-beta play each critical role in the different phases of PLM-induced pulmonary fibrosis by inducing fibroblast proliferation and transformation, respectively.

Actins↗

PubMed2001

A novel bovine lactoferrin peptide, FKCRRWQWRM, suppresses Candida cell growth and activates neutrophils.

To identify potent new antifungal agents, the Candida cell growth inhibitory activities of six lactoferrin (Lf) peptides consisting of 6-25 amino acid residues (peptide 1, FKCRRWQWRMKKLGAPSITCVRRAF lactoferricin B; peptide 2, FKCRRWQWRM; peptide 2', FKARRWQWRM; peptide 3, GAPSITCVRRAF; peptide 4, RRWQWR; and peptide 5, RWQWRM) were examined. Of these, peptide 2 strongly suppressed the multiplication of Candida cells, but other peptides showed only weak activities. In two strains of C. albicans, the minimum inhibitory concentration 100 of peptide 2 (17.3+/-2.2 microM and 17.5+/-2.4 microM) was close to that of miconazole (13.0+/-1.7 microM and 13.1+/-1.6 microM) but markedly different from that of amphotericin B (0.52+/-0.09 microM and 0.56+/-0.11 microM). The suppression of Candida cell growth was additively increased by a combination of peptide 2 with amphotericin B and miconazole. Peptides 1, 3, 4 and 5 and Lf suppressed iron uptake by Candida cells, inversely correlated with their Candida cell growth inhibition activities. However, iron uptake was not inhibited by peptide 2. In addition, peptide 2 upregulated Candida cell killing activity of polymorphonuclear leukocytes (PMN) increasing their superoxide generation, protein kinase C activity, p38 MAPK activity and the expression of p47phox. These results indicated that the main antimicrobial activity of the Lf peptides is dependent on the N-terminal half of Lf and that the PMN upregulatory activity of peptide 2 and additive function of peptide 2 with antifungal drugs are useful for prophylaxis and control of candidiasis.

Amino Acid Sequence↗

PubMed2001

Lactoferrin peptide increases the survival of Candida albicans-inoculated mice by upregulating neutrophil and macrophage functions, especially in combination with amphotericin B and granulocyte-macrophage colony-stimulating factor.

To develop a new strategy to control candidiasis, we examined in vivo the anticandidal effects of a synthetic lactoferrin peptide, FKCRRWQWRM (peptide 2) and the peptide that mimics it, FKARRWQWRM (peptide 2'). Although all mice that underwent intraperitoneal injection of 5 x 10(8) Candida cells with or without peptide 2' died within 8 or 7 days, respectively, the survival times of mice treated with 5 to 100 microg of intravenous peptide 2 per day for 5 days after the candidal inoculation were prolonged between 8.4 +/- 2.9 and 22.4 +/- 3.6 days, depending on the dose of peptide 2. The prolongation of survival by peptide 2 was also observed in mice that were infected with 1.0 x 10(9) Candida albicans cells (3.2 +/- 1.3 days in control mice versus 8.2 +/- 2.4 days in the mice injected with 10 microg of peptide 2 per day). In the high-dose inoculation, a combination of peptide 2 (10 microg/day) with amphotericin B (0.1 microg/day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 microg/day) brought prolonged survival. With a combination of these agents, 60% of the mice were alive for more than 22 days. Correspondingly, peptide 2 activated phagocytes inducing inducible NO synthase and the expression of p47(phox) and p67(phox), and peptide 2 increased phagocyte Candida-killing activities up to 1.5-fold of the control levels upregulating the generation of superoxide, lactoferrin, and defensin from neutrophils and macrophages. These findings indicated that the anticandidal effects of peptide 2 depend not only on the direct Candida cell growth-inhibitory activity, but also on the phagocytes' upregulatory activity, and that combinations of peptide 2 with GM-CSF and antifungal drugs will help in the development of new strategies for control of candidiasis.

Amphotericin B↗

PubMed2001

Prediction of pulmonary complications after a lobectomy in patients with non-small cell lung cancer.

BACKGROUND: Although the preoperative prediction of pulmonary complications after lung major surgery has been reported in various papers, it still remains unclear. METHODS: Eighty nine patients with stage I-IIIA non-small cell lung cancer (NSCLC) who underwent a complete resection at our institute from 1994-8 were evaluated for the feasibility of making a preoperative prediction of pulmonary complications. All had either a predicted postoperative forced vital capacity (FVC) of >800 ml/m(2) or forced expiratory volume in one second (FEV(1)) of >600 ml/m(2). RESULTS: Postoperative complications occurred in 37 patients (41.2%) but no patients died during the 30 day period after the operation. Pulmonary complications occurred in 20 patients (22.5%). Univariate analysis indicated that the factors significantly related to pulmonary complications were FVC <80%, serum lactate dehydrogenase (LDH) level > or =230 U/l, and arterial oxygen tension (PaO(2)) <10.6 kPa (80 mm Hg). In a multivariate analysis the three independent predictors of pulmonary complications were serum LDH > or =230 U/l (odds ratio (OR) 10.5, 95% CI 1.4 to 77.3), residual volume (RV)/total lung capacity (TLC) > or =30% (OR 6.0, 95% CI 1.1 to 33.7), and PaO(2) <10.6 kPa (OR 5.6, 95% CI 1.4 to 22.2). CONCLUSIONS: The above findings indicate that three factors (serum LDH levels of > or =230 U/l, RV/TLC > or =30%, and PaO(2) <10.6 kPa) may be associated with pulmonary complications in patients undergoing a lobectomy for NSCLC, even though the patient group was relatively small for statistical analysis of such a diverse subject as pulmonary complications.

Adult↗

PubMed2001

Peripheral lung adenocarcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival.

PURPOSE: To evaluate the prognostic importance of thin-section computed tomographic (CT) findings of peripheral lung adenocarcinomas. MATERIALS AND METHODS: The subjects were 127 patients with adenocarcinomas smaller than 3 cm in largest diameter who underwent at least a lobectomy with hilar and mediastinal lymphadenectomy. The margin characteristics of nodules and the extent of ground-glass opacity (GGO) within the nodules at preoperative thin-section CT were analyzed retrospectively. Regional lymph node metastasis (LNM) and vessel invasion (VI) were histologically examined in surgical specimens. Survival curves were calculated according to the Kaplan-Meier method. RESULTS: The frequencies of LNM (4% [1 of 24]) and VI (13% [three of 24]) in adenocarcinomas with GGO components of more than 50% were significantly lower than those with GGO components of less than 10% (LNM, P <.05; VI, P <.01). The patients with GGO components of more than 50% showed a significantly better prognosis than those with GGO components less than 50% (P <.05). All 17 adenocarcinomas smaller than 2 cm with GGO components of more than 50% were free of LNM and VI, and all these patients are alive without recurrence. Coarse spiculation and thickening of bronchovascular bundles around the tumors were observed more frequently in tumors with LNM or VI than in those without LNM or VI (P <.01). CONCLUSION: Thin-section CT findings of peripheral lung adenocarcinomas correlate well with histologic prognostic factors.

Adenocarcinoma↗

PubMed2001

Microsatellite instability in transforming growth factor-beta 1 type II receptor gene in alveolar lining epithelial cells of idiopathic pulmonary fibrosis.

It has been reported that transforming growth factor (TGF)-beta, which plays an integral role in the pathogenesis of idiopathic pulmonary fibrosis (IPF), suppresses proliferation of alveolar epithelial cells in vitro. Although hyperplastic lesions of alveolar lining epithelial cells (ALECs) are characteristic pathologic features of IPF, the mechanism of their involvement in the pathogenesis has not yet been extensively studied. On the assumption that the hyperplastic ALECs have escaped from the growth-inhibitory effects of TGF-beta, we searched for mutations in the microsatellite of the TGF-beta receptor type II (T beta RII) gene. To detect a deletion in the polyadenine tract in exon 3 of the T beta RII gene, cells were isolated by microdissection from lung sections of IPF patients, and DNA was extracted from these cells and amplified by high-fidelity polymerase chain reaction. A total of 121 sites of hyperplastic ALECs from 11 IPF patients were analyzed, and a one-base-pair deletion was detected in nine sites from five patients. The mutation was also detected in smooth muscle-like cells of the thickened pulmonary artery. In some tissue areas where the deletion was detected, low T beta RII expression was confirmed by immunohistochemical staining. These data suggest that microsatellite instability in the T beta RII gene occurred in some lesions of hyperplastic ALECs in IPF, although at a low incidence, and that this genetic disorder might play a partial role in the pathologic changes of IPF.

Adult↗

PubMed2001

The upregulation by peplomycin of signal transduction in human cells.

To explore the mechanism of pulmonary fibrosis by bleomycin and its derivative, peplomycin (PLM), we examined the influence of PLM on signal transduction in human peripheral blood lymphocytes (HL), monocytes (HM) and fibroblasts (HF). Tyrosine phosphorylation of multiple proteins in HL and HM were induced by 0.001 to 0.05 microg/ml and by 0.01 to 0.5 microg/ml of PLM, respectively. In HF, 116-kDa protein was phosphorylated 0.2 to 5 microg/ml of PLM. When HL were treated with 0.01 microg/ml of PLM, phosphorylation of p56lck and activation of extracellular-signal related kinase-2 (ERK2) were induced. ERK2 was also activated in HM. Coordinately, the ratio of p21ras-binding GTP/GDP was increased by PLM. As well as interleukin-2, PLM induced tyrosine phosphorylation of JAK-3. In addition, PLM upregulated the nuclear translocation of nuclear factor-kappa B and the expression of c-myc-mRNA in HL, HM and HF. Furthermore, 0.01 to 0.001 microg/ml PLM enhanced the cytokine generation by HL and HM, and 1 to 5 microg/ml PLM increased cytokine generation and collagen synthesis by HF. These upregulatory effects of PLM were abrogated by pretreatment of the cells with a tyrosine kinase inhibitor. These results indicate that PLM upregulates signal transduction in a variety of cell types and the upregulation may induce pulmonary fibrosis.

Antibiotics, Antineoplastic↗

PubMed2001

Improvement of anti-Hu-associated paraneoplastic sensory neuropathy after chemoradiotherapy in a small cell lung cancer patient.

A 66-year-old man developed progressive painful dysesthesia in his hands and feet over 3 months. His vibration sense was impaired and sensory nerve action potentials of the limbs were not evoked. Biopsy of the peroneal nerve revealed sensory neuropathy. Positive anti-Hu antibody facilitated delineation of a right hilar mass and a metastatic lymph node in thoracic CT scan. He was diagnosed as small cell lung cancer associated with paraneoplastic sensory neuropathy. A complete response was achieved through chemotherapy (carboplatin and etoposide) and subsequent radiation therapy. Notably, his neurological conditions, although not changed during the hospitalization, gradually improved afterwards.

Aged↗

PubMed2001

[Influence of peplomycin on pulmonary function (PaO2, %DLco) in patients with oral carcinoma].

The pathogenesis of pulmonary fibrosis (PF) induced by bleomycin and its derivative, peplomycin (PEP), is insufficiently understood. To prevent PF and to administer PEP safely, we examined the influence of PEP on pulmonary function in 135 patients who underwent concomitant chemo (PEP + 5-FU)-radio (60Co) therapy and pulmonary function tests. In the inductive therapy, 5 mg of PEP was intramuscularly injected three times a week and a total of 41.6 +/- 14.3 mg was administered. Of the patients, 98 received oral azelastine hydrochloride (AZH, 4 mg/day) during the inductive therapy with the aim of prophylaxis of PF. The oxygen partial pressure in arterial blood (PaO2) only slightly decreased from 84.2 +/- 12.1 mmHg before treatment to 82.8 +/- 12.5 mmHg after treatment, while, carbon oxide diffusion (%DLco) decreased after treatment in most patients (p < 0.001, by paired t test) with mean values before treatment of 106.3 +/- 24.5% and after treatment 99.5 +/- 24.9%. The decrease of %DLco was associated with the dose of PEP until about 40 mg but further decreases of %DLco were not prominent. In the patients who underwent oral AZH, the decrease of %DLco weaker than that in patients without AZH: the decrease rates of %DLco in the former and latter were 4.3 +/- 9.4% and 14.1 +/- 15.9%, respectively. From the chest X-ray examination, mild PF was suspected in three patients but no advancement of PF or clinical symptoms were observed. From these results, it was concluded first that %DLco is more useful than PaO2 as the predisposing risk factor for PF, second that the decrease of %DLco depends on the dose of PEP until about 40 mg, third that AZH is expected to inhibit PEP-induced PF, and fourth that a small dose (20-40 mg) of PEP can be administered without inducing PF if care is exercised as to the patient's age, general condition and the value of %DLco in the use of PEP.

Aged↗

PubMed2001

Nuclear expression of the Y-box binding protein, YB-1, as a novel marker of disease progression in non-small cell lung cancer.

Transcription factor Y-box binding protein 1 (YB-1) that binds to the inverted CCAAT box is involved not only in transcription of various genes but also in cell proliferation and DNA repair. We determined whether localization of YB-1 in either the nucleus or cytoplasm could serve as a prognostic marker for patients with non-small cell lung cancer (NSCLC). In 196 NSCLC patients, expression of YB-1 protein in the nucleus or cytoplasm was immunohistochemically evaluated. Of the 196 tumors examined, 88 (44.9%) were positive for YB-1 expression in the nucleus. Nuclear YB-1 expression significantly correlated with T factor, lymph node metastasis, and stage of the disease. Patients with a nuclear YB-1 tumor had a poorer prognosis than did those with a cytoplasmic YB-1 tumor in all of the NSCLC patients (P = 0.0494) and in patients with squamous cell carcinoma (P = 0.0313) but not in patients with adenocarcinomas. Nuclear localization of the YB-1 protein may prove to be an important factor of disease progression for patients with NSCLC, in particular, in cases of squamous cell carcinoma.

Adenocarcinoma↗

PubMed2000

Benign mesenchymoma of the mediastinum.

We report our recent experience of a rare case of a benign mesenchymoma in the mediastinum. A 24-year-old man was admitted to our hospital with an abnormal shadow on chest X-ray. A chest computerized tomography scan and magnetic resonance imaging showed an anterior mediastinal mass along the right border of the pericardium. The tumor was surgically resected. It was yellow on the surface, 12.5 x 10.0 x 3.8 cm in size, and 230 g in weight. The histopathological diagnosis was a benign mesenchymoma. The postoperative course was uneventful. A search of the literature revealed that a benign mesenchymoma in the mediastinum is extremely rare. It seems to be difficult to reach a definitive diagnosis preoperatively. Surgical resection can confirm the diagnosis, and is curative.

Adult↗

PubMed2000

Enhanced apoptosis of squamous cell carcinoma cells by interleukin-2-activated cytotoxic lymphocytes combined with radiation and anticancer drugs.

Induction of potent apoptosis is required in cancer therapy. We examined the combination effect of interleukin-2-activated lymphocytes (LAK cells) and anticancer drugs or gamma (gamma)-rays on the induction of apoptosis in an established oral squamous cell carcinoma cell line (OSC-3 cells). By pretreatment of OSC-3 cells with (137)Cs (5 Gy), 5-fluorouracil (5-FU) (0.5 microg/ml) or cis-dichlorodiammine-platinum (CDDP) (5 microg/ml), the activation of bid and caspase-3 by LAK cells was strongly increased and associated with an enhanced degradation of poly-(ADP-ribose) polymerase (PARP) and/or nuclear mitotic apparatus protein (NuMA) and the increased fragmentation of DNA. The LAK cell-enhanced caspase-3 activity in the pretreated OSC-3 cells was decreased to approximately 70% and 40% of the control by the addition of Z-AAD-CMK (a granzyme B inhibitor) and neutralising monoclonal antibody to Fas antigen (alphaFas-IgG), respectively. The combined treatment-induced DNA fragmentation was suppressed by approximately 20% and 30% of the control by the addition of Z-AAD-CMK and alpha Fas-IgG, respectively, in the co-culture system. While Ac-DEVD-CHO (a caspase-3 inhibitor) suppressed the DNA fragmentation levels to approximately half and this was similar to the amount of suppression that was obtained by the addition of both alpha Fas-IgG and Z-AAD-CMK. In addition, LAK cell-activated bid may have increased the intracellular reactive oxygen intermediates (ROI) level and induced a decrease of mitochondrial membrane potential. These influences by LAK cells were enhanced when OSC-3 cells were pretreated with each anticancer drug or (137)Cs. Furthermore, the increase of ROI by LAK cells was suppressed by alpha Fas-IgG and Z-AAD-CMK to approximately half the level of the control. These results indicate that anticancer drugs and gamma-rays prime squamous cell carcinoma cells to be susceptible to apoptosis by LAK cells, that LAK cell-induced apoptosis largely depends on the activation of caspase-3 by the Fas/Fas-ligand signal and granzyme B, and that LAK cells induce ROI in the target cells, which is largely mediated by Fas and granzyme B.

Antineoplastic Agents↗

PubMed2000

Pulmonary lymphangitic carcinomatosis from an oropharyngeal squamous cell carcinoma: a case report.

Pulmonary lymphangitic carcinomatosis (PLC), a form of lymphatic spread of cancer cells, from head and neck cancers is extremely rare. We report here a case of PLC from an oropharyngeal squamous cell carcinoma in a 68-year-old man. The patient underwent inductive chemoradioimmunotherapy which resulted in complete tumor remission. The tumor, however, recurred 6 months later and was resected. Late metastasis occurred in the ipsilateral cervical lymph nodes 13 months post surgery and these lymph nodes were dissected. Three months later, the patient suffered from a fever, cough and dyspnea and a chest radiograph revealed an interstitial linear pattern from the right hilum to the right upper lung field. Without diagnosis of the pulmonary lesion, swelling of the bilateral lymph nodes followed after a few months and dyspnea worsened with spread of the reticular shadow and appearance of Kerley's B line on the roentgenogram, suggesting PLC. The patient gradually became more distressed and finally died 6 months after the onset of dyspnea. The microscopy of the autopsied pulmonary tissue revealed tumor cell nests in the lymph vessels in the septa and the pulmonary lesion was histopathologically diagnosed as PLC. The present case indicates that we should consider PLC when cough and dyspnea with reticular shadows and Kerley's B line are observed in patients with head and neck carcinoma.

Aged↗

PubMed2000

The mechanism of mononuclear cell infiltration in oral lichen planus: the role of cytokines released from keratinocytes.

To clarify the pathogenesis of oral lichen planus (OLP), we investigated the roles of keratinocytes (KC) in mononuclear cell infiltration. When peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence of culture supernatants of KC separated from the noninflamed gingivae (Nor-KC) and cheek mucosae of patients with OLP (OLP-KC), the number of migrated PBMC across monolayered human umbilical vein endothelial cells (HUVEC) were increased to about 1.3-fold and 1.5-fold of the control level, respectively, with increases of the expression of CD11a, CD11b, CD18, and CD49d on PBMC and intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVEC. The number of migrated PBMC was reduced to about 60% of the control level by pretreatment of PBMC with anti-CD11a or anti-CD18 MAb and reduced to about 70% by pretreatment of HUVEC with anti-CD54 MAb. The pretreatment of PBMC with genistein, H-7, wortmannin, or exoenzyme C3 decreased the migrated PBMC by about 70 to 90%. In agreement with these results, the culture supernatants of OLP-KC up-regulated tyrosine phosphorylation of 62-kDa, 70-kDa, and 102-kDa proteins, phosphatidylinositol-3 kinase, and protein kinase C activities and activated Rho protein level more so than did those of Nor-KC. Additionally, actin reorganization with the formation of membrane ruffles and lamellipodia was distinctly induced by the culture supernatants of OLP-KC. These results indicate that cytokines generated by KC transduce their signals in PBMC, up-regulating the expression of cell surface adhesion molecules and migration activity with reorganization of actin filaments.

Actin Cytoskeleton↗

PubMed2000

Plaunotol suppresses interleukin-8 secretion induced by Helicobacter pylori: therapeutic effect of plaunotol on H. pylori infection.

BACKGROUND: It has been suggested that gastric mucosal injury induced by Helicobacter pylori infection is mediated by interleukin-8 (IL-8). METHODS: We studied the effect of plaunotol, a drug extracted from the Plau-noi tree of Thailand, and reported it to be effective in the treatment of ulcers, of IL-8 secretion induced by H. pylori and of the inhibitory adhesion activity of the bacterium to gastric epithelial cells. Moreover, the therapeutic effect of plaunotol on H. pylori infection was assessed by using the gnotobiotic murine model. RESULTS: Plaunotol inhibited the growth of H. pylori (1.5 x 10(4) c.f.u./mL) at high doses (24-48 microg/mL), but not at low doses (3-6 microg/mL). Interleukin-8 secretion induced by H. pylori was inhibited by coculture with plaunotol in a dose-dependent manner. The adhesion of H. pylori to MKN45 cells was also suppressed by coculture with plaunotol in a dose-dependent manner. An in vivo study showed that plaunotol improved histological gastritis and decreased the H. pylori antibody titre. CONCLUSIONS: These findings suggest that plaunotol has a therapeutic effect on gastritis induced by H. pylori.

Administration, Oral↗

PubMed2000

Regulation of Candida albicans growth and adhesion by saliva.

To examine the local regulation of oral Candida albicans growth, we examined non-stimulated and stimulated salivary flow rates (SFRs) and the C. albicans growth and adhesion inhibitory activities of saliva in 60 patients with oral candidiasis (divided into two groups: 25 patients with oral candidiasis only (group OC) and 35 patients with oral candidiasis and systemic diseases (group CS)) and 30 healthy control subjects. Both non-stimulated and stimulated SFRs in patients, especially in group CS; were decreased in comparison with those in the healthy control subjects. The levels of secretory immunoglobulin A (sIgA) in group OC and group CS and the lactoferrin level in group CS were decreased as compared with those in control individuals, although there were no differences in transferrin and total secretory component (SC) levels between the three groups. The secretion amounts (microg/min) of these proteins were statistically significantly decreased in the patients, especially in group CS. Saliva from the patients showed a lesser inhibitory effect on C. albicans growth and adhesion to HeLa cells than did saliva from the control subjects. In addition, polymorphonuclear leukocytes (PMNs) in patients' saliva generated smaller amounts of superoxide than did those in control subjects' saliva, and phagocytic and C. albicans killing activities were suppressed in the patients. These results indicate that the decreases in SFR, secretion of antimicrobial proteins in saliva, and salivary PMN activity are risk factors for oral candidiasis associated with aging and systemic diseases.

Adult↗