Biomedical subjects

S Takeno

Publications and source records attributed to S Takeno.

At least 37 records · Page 2Linked to original sources

PubMed2001

Increased nitric oxide production in nasal epithelial cells from allergic patients--RT-PCR analysis and direct imaging by a fluorescence indicator: DAF-2 DA.

BACKGROUND: Nitric oxide (NO) is believed to participate in the regulation of airway clearance and non-specific cellular immunity. Recent studies have suggested that airway epithelial cells of allergic and non-allergic individuals may differ in their ability to produce this molecule. OBJECTIVE: The aim of this study was to detect the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess the relationship between the expression of nitric oxide synthase (NOS) isoforms and the severity of the disease. METHODS: Nasal epithelial cells were obtained from the inferior turbinate. The expression of mRNAs encoding constitutive endothelial NOS (eNOS) and inducible NOS (iNOS) was studied by reverse transcription-polymerase chain reaction (RT-PCR). Direct NO production in living cells was visualized and quantified by a fluorescent indicator, DAF-2 DA. RESULTS: RT-PCR analysis demonstrated that AR patients with a RAST score of 5 or 6 showed significant increases in the levels of iNOS mRNA and slight reductions in those of eNOS mRNA. Patients with a RAST score of 2-4 also revealed the same tendency however, the difference was not significant. DAF-2 DA imaging demonstrated that epithelial cells, especially the ciliated cells, produced a larger amount of NO than non-epithelial inflammatory cells. Preincubation with L-NAME resulted in an approximate 40% decrease in both groups. CONCLUSION: These results directly indicate that nasal epithelial cells of AR patients overall produce higher levels of NO through the concomitant expression of different NOS isoforms. Continuous NO production by the epithelial cells in normal subjects further support the hypothesis that NO derived from epithelium may play dual roles in the regulation of nasal airway clearance and in the host defense. In addition, the use of DAF-2 DA provides a reliable method to visualize and quantify the direct NO production of living cells.

Actins↗

PubMed2001

Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome.

AIMS: The cadherin-catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally beta-catenin (beta-ct) can also take part in signal transduction and nuclear beta-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of beta-ct is still uncertain, we investigated the expression pattern of beta-ct as well as the possible prognostic role. METHODS AND RESULTS: beta-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous beta-ct expression similar to that in normal gastric mucosa. In 80 tumours beta-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous beta-ct expression was found. Additionally, in 53 tumours, a strong beta-ct expression could be observed in the cytoplasm with a simultaneous nuclear beta-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous beta-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different beta-ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear beta-ct expression. CONCLUSION: Our data on 401 tumours suggest that activation of the Wnt/beta-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear beta-ct expression nor the reduction or loss of membranous beta-ct expression is correlated with a specific histological tumour type, tumour progression or prognosis.

Cell Division↗

PubMed2001

Immunohistochemical and clinicopathologic analysis of response to neoadjuvant therapy for esophageal squamous cell carcinoma.

Recently, neoadjuvant chemotherapy combined with radiation (NAT) has been used in the active treatment of progressive esophageal cancer (T4). However, many patients are resistant to supplemental therapy, and it is necessary to to be aware that side-effects may occur. Accordingly, to minimize adverse reactions and cost, it is important to determine the indications for NAT. We investigated 34 patients with T4 esophageal squamous cell carcinoma and examined the relation between the effects of NAT and immunohistochemical or additional clinicopathologic factors. There was no relation between clinicopathologic factors and immunohistochemical findings (p53 or hsp27 expression), and no clinicopathologic factors showed a relation to a supplemental therapeutic effect. In addition, there was no correlation between p53 staining and therapeutic effects (P=0.734). In contrast, there was a correlation (P=0.0058) between hsp27 staining and therapeutic effect. In conclusion, the usefulness of hsp27 immunostaining in predicting the therapeutic effect of NAT was confirmed in T4 esophageal squamous cell carcinoma.

Adult↗

PubMed2001

Functional role of nitric oxide in the nasal mucosa of the guinea pig after instillation with lipopolysaccharide.

Nitric oxide (NO) has been found to have various actions in the body. Recently, considerable attention has been focused on the intimate relationship between the intracellular production of NO and morphological or functional changes in ciliated cells. The aim of this study was to clarify the functional significance of NO in the nasal mucosa. Healthy, adult, pigmented guinea pigs were randomly divided into one control and three experimental groups. The animals were instilled with either lipopolysaccharide (LPS) only or LPS plus dexamethasone or NG-nitro L-arginine methyl ester (L-NAME). The effect of NO on the nasal epithelium was analyzed morphologically by scanning electron microscopy and physiologically by ciliary beat frequency (CBF) measurement. The origin of NO was also investigated using a fluorescent indicator for NO, namely 4,5-diaminofluorescein diacetate. LPS induced damage of cilia 3 days after the first instillation, while dexamethasone or L-NAME seemed to attenuate the effect of LPS. NO production was localized in ciliated cells and the main source of NO in ciliated cells is suggested to be inducible NO synthase. The greater number of ciliated cells of LPS-treated animals produced a larger amount of NO compared with normal animals. LPS also induced a decrease in CBF, which was inhibited by dexamethasone or L-NAME. It is suggested that NO may play an important role in pathological changes in the nasal mucosa.

Animals↗

PubMed2000

Injury to the gastric mucosa and cellular dynamics in a rat model of duodenogastric reflux: the possible significance of gastrin induction and a heat shock protein.

Injury to the gastric mucosa caused by duodenogastric reflux (DGR) is often encountered after gastrectomy or truncal vagotomy (V) with pyloroplasty. This study was designed to investigate the histological features of the gastric mucosa under such conditions. A rat model of DGR and DGR+V was established and the thickness of the oxyntic mucosa was measured. Cellular dynamics in the presence of injury to the gastric mucosa caused by DGR were investigated by the immunohistochemical staining of bromodeoxyuridine (BrdU) and heat shock protein 70 (HSP70). The relationship between persistent hypergastrinemia and mucosal injury was also studied. Duodenogastric reflux activated the intracellular induction of HSP70 in our rat model of DGR. Hypergastrinemia was noted in the V group. Compared with values from the DGR group, the numbers of BrdU-labeled cells increased, the glandular proliferation zone expanded, and the thickness of the oxyntic mucosa was significantly higher in the DGR+V group. Compared with the DGR group, there was greater induction of HSP in the DGR+V group during the acute stage. This finding suggests that denervation of the gastric mucosa and hypergastrinemia after vagotomy may be associated with the expression of HSP.

Animals↗

PubMed2000

Development of an inveterate gastroduodenal ulcer caused by antral G-cell hyperplasia of the stomach (pseudo-Zollinger-Ellison Syndrome): report of a case.

We describe herein the case of a 54-year-old Japanese woman in whom an inveterate peptic ulcer developed in association with pseudo-Zollinger-Ellison Syndrome (pseudo-ZES). The patient presented with weight loss and abdominal distension caused by antral and duodenal stenosis due to an inveterate peptic ulcer. Her serum gastrin level was very high; however, no evidence of a gastrinoma or carcinoid tumor was detected by preoperative examinations or surgery. A total gastrectomy and double-tract reconstruction was performed, and pathological examination revealed a gastric ulcer (UL-IV) with no histopathological evidence of a neoplasm. Immunohistochemical staining showed an obvious increase in the number of endocrine cells that were positive for chromogranin A, and marked G-cell hyperplasia was observed in the antral mucosa. Furthermore, the number of enterochromaffin-like cells was remarkably high. From the results of the immunohistochemical examination, the patient was diagnosed as having hypergastrinemia due to antral G-cell hyperplasia. Postoperatively, the patient's serum gastrin level fell rapidly to within the normal range, her nutritional status improved, and her weight increased by about 10 kg within 1 year.

Diagnosis, Differential↗

PubMed2000

Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma.

We investigated whether the expression of membrane-type-1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was consistent with the proposed roles of these proteins in promoting metastasis in colorectal cancer. The expression of MT1-MMP was significantly more frequent in deeply invasive carcinomas (P = 0.007) and in cases of vascular invasion (P = 0.02). The frequency of detection of MMP-2 in the stroma was much greater in vascular invasion-positive cases (42%) than in negative cases (20%; P = 0.02). The rate of detection of TIMP-2 in tumour cell cytoplasm increased with the depth of invasion (P = 0.03). TIMP-2 in the stroma was found more frequently in tumours with lymphatic invasion and lymph node metastasis (P < 0.05). Significant correlations were found between detection of MT1-MMP and MMP-2 in tumour cell cytoplasm (P < 0.05), of MT1-MMP and TIMP-2 in tumour cell cytoplasm (P < 0.01), and of MMP-2 and TIMP-2 in tumour cell cytoplasm (P < 0.01). Immunohistochemical detection of MT1-MMP and TIMP-2 might be useful for monitoring infiltration in colorectal carcinoma but is not correlated with distant metastases.

Adenocarcinoma↗

PubMed2000

Analysis of local cytokine gene expression in patients with allergic rhinitis treated with CO2 laser surgery.

OBJECTIVES/HYPOTHESIS: Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms. STUDY DESIGN: A prospective analysis of 25 patients with allergic rhinitis caused by the house dust mite who underwent laser surgery twice with a 1-month interval on an outpatient basis. Fifteen healthy volunteers served as normal control subjects. METHODS: Improvement of the nasal symptoms was evaluated on a graded scale. Nasal mucosal cells were obtained by brushing from the inferior turbinate at each visit. The expression of messenger RNA (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, RANTES (regulated on activation, normal T-cell expressed and secreted), and eotaxin was semiquantitatively analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Two months after treatment, the nasal symptom scores significantly decreased from baseline. The decrease was most apparent in nasal obstruction. RT-PCR analysis revealed that a significant decrease in IL-8 and RANTES expression (P < .001 and P = .012, respectively) was observed after successive laser treatment, and the reduction in these cytokines was significantly correlated. On the other hand, mRNA expression of GM-CSF, IL-6, and eotaxin remained unchanged. CONCLUSIONS: This study provided evidence that the expression of local inflammatory cytokines can be attenuated in part by CO2 laser treatment, which may be closely related to the clinical effectiveness of this procedure.

Adult↗

PubMed2000

Multiple gastric carcinomas 21 years after gastrojejunostomy without gastrectomy. Report of a case.

We report a case of gastric carcinoma after gastrojejunostomy (GJ-stomy) without gastrectomy. Multiple gastric carcinomas were discovered 21 years after GJ-stomy without gastrectomy which had been performed for treatment of pyloric stenosis due to severe gastric ulcer. Multiple gastric carcinomas were found in the stomach, or the esophagocardiac junction, and in the corpus and anastomotic lesion of the GJ-stomy. Under the light microscope, intestinal metaplasia was detected in the antral mucosa and the area around the anastomosis. In immunohistochemical analysis, p53-specific antibodies gave a positive reaction in every gastric carcinoma and in the noncancerous gastric glands around the carcinoma at the anastomosis and in the corpus. Cells positive for immunostaining with Ki-67-specific antibodies were more numerous in all gastric carcinomas and in the area around the anastomotic lesion than in the normal gastric mucosa. Hsp70-specific antibodies reacted with cells in the noncancerous glands around the carcinoma in the anastomotic area. Mucosal injury and the potential for carcinogenesis due to exposure to gastroduodenal reflux are discussed. The results of this study suggest that similar cases with gastroduodenal reflux should be followed carefully.

Adenocarcinoma↗

PubMed2000

Modulation of ciliary activity by tumor necrosis factor-alpha in cultured sinus epithelial cells. Possible roles of nitric oxide.

The primary function of well-differentiated ciliated epithelium in the paranasal sinus is to eliminate harmful agents through the beating action of cilia. Respiratory epithelium also contributes to local inflammatory processes through the release of various proinflammatory cytokines. Recently, considerable attention has been focused on the intimate relationship between the cytokine-dependent regulation of the ciliary beat frequency (CBF) and intra-cellular production of nitric oxide (NO) in ciliated epithelial cells. The aims of this study are to examine the effect of tumor necrosis factor-alpha (TNF-alpha), one of the major proinflammatory cytokines, on the ciliary activity of human sinus epithelial cells and to assess the hypothesis that NO is involved in this regulatory mechanism. Human maxillary or ethmoidal sinus mucosa (n = 23) were cultured by the explant-outgrowth method. CBF of the outgrowth ciliated cells was measured by the photoelectrical method before and after being treated with TNF-alpha (0.1, 1 and 10 ng/ml) or dexamethasone (10(-6) M and 10(-7) M). We also investigated the expression of nitric oxide synthase (NOS) isoforms, enzymes responsible for NO synthesis, by fluorescent immunohistochemistry. TNF-alpha increased CBF at relatively low concentrations (0.1 and 1 ng/ml) and decreased CBF at a high concentration (10 ng/ml). Dexamethasone decreased CBF at a concentration of 10(-6) M. Fluorescent immunohistochemistry demonstrated that the expression of inducible NOS was augmented by TNF-alpha and attenuated by dexamethasone, whereas that of endothelial NOS remained unchanged. We conclude that human sinus epithelial cells potentially contribute to the inflammatory process by regulating their ciliary motility through an NO-dependent pathway. Proinflammatory cytokines and steroids are able to modulate this mechanism by the induction or inhibition of expression of different NOS isoforms.

Cells, Cultured↗

PubMed1999

Increased expression of inducible nitric oxide synthase in nasal epithelial cells in patients with allergic rhinitis.

OBJECTIVES: Although ciliated epithelial cells of human nose and paranasal sinuses have recently been reported to be the major source of locally detected nitric oxide (NO), changes to the NO production by these cells and their functional roles remain uncertain in relation to allergic rhinitis. The objective of this study is to investigate differences in the ability of induction of nitric oxide synthase (NOS) isoforms by nasal epithelial cells. STUDY DESIGN: Epithelial cells of the inferior turbinate taken from 12 normal subjects and 12 allergic patients against house dust mite were used. Samples from the house dust group were taken both before and after antigen provocation. METHODS: Immunoreactivity for two NOS isoforms, inducible NOS (iNOS) and endothelial NOS (eNOS), was examined by the laser scanning confocal microscope. The labeled cells were processed into digital images, and the fluorescence intensity was assessed quantitatively. RESULTS: The degree of iNOS expression of the epithelial cells was significantly elevated in the house dust group compared with that of the control group. The expression appeared identical both before and after antigen provocation in the house dust group. On the other hand, there was no significant difference in eNOS expression between the two groups. CONCLUSIONS: We assume that the increased iNOS expression of the epithelial cells in the house dust group might result from stimulated secretion of proinflammatory cytokines during allergic responses. This further suggests profound contribution of nasal epithelial cells to modifying the airway clearance through the production of high levels of NO.

Adult↗

PubMed1999

Stationary dark localized modes: discrete nonlinear Schrödinger equations.

Various kinds of stationary dark localized modes in discrete nonlinear Schrödinger equations are considered. A criterion for the existence of such excitations is introduced and an estimation of a localization region is provided. The results are illustrated in examples of the deformable discrete nonlinear Schrödinger equation, of the model of Frenkel excitons in a chain of two-level atoms, and of the model of a one-dimensional Heisenberg ferromagnetic in the stationary phase approximation. The three models display essentially different properties. It is shown that at an arbitrary amplitude of the background it is impossible to reach strong localization of dark modes. In the meantime, in the model of Frenkel excitons, exact dark compacton solutions are found.

Journal Article↗

PubMed1998

Localization of nitric oxide synthase in human nasal mucosa with nasal allergy.

Nitric oxide (NO) plays an important role in the regulation of upper respiratory function. In the nasal cavity, the concentration of NO in the air in patients with untreated allergic rhinitis is higher than that in normal individuals. NO is produced by the action of NO synthase (NOS) using L-arginine as a substrate. To investigate the expression of NOS in human nasal mucosa, histochemical staining for NADPH diaphorase and immunohistochemical staining for NOS isoforms were carried out in nasal inferior turbinate mucosa from patients with nasal allergy. Those without nasal allergy served as controls. NADPH diaphorase histochemical study revealed that NOS was expressed in the nasal epithelium, submucosal glands, nerve fibres and the endothelium in specimens of both allergic and control groups. Immunoreactivity to endothelial NOS (eNOS) was localized to epithelial and endothelial cells in both allergic and control groups. In some specimens in both groups, nerve fibres around submucosal glands stained positively for eNOS. Immunoreactivity to eNOS, however, was slightly stronger in the epithelia of the allergic group than in those of the controls. Immunoreactivity to inducible NOS (iNOS) was localized to epithelial cells, endothelial cells, nasal glands and inflammatory cells. The staining of epithelial cells and inflammatory cells was more marked in the allergic group than the controls. These findings may suggest that the greater amounts of NO in the nasal air of patients with allergic rhinitis are mainly induced by iNOS activity.

Case-Control Studies↗

PubMed1998

[Decongesting effect of tramazoline on nasal airway patency and nasal symptoms as evaluated by acoustic rhinometry: an objective study in 30 allergic and six non-allergic subjects].

In this prospective clinical study, we investigated the effect of the nasal decongestant tramazoline on nasal airway patency in 30 subjects with perennial nasal allergy to housedust mites and in six non-allergic volunteers who served as controls. The allergic subjects were further subdivided into groups, the severe group and the moderate group, according to the level of specific IgE. We used acoustic rhinometry as an objective method, and the nasal cavity volume (NCV) and the minimum cross-sectional area (MCA) were measured before and 10 minutes after nasal spraying. Before mucosal decongestion, the average NCV in the severe group was 5.94 cm3, which was significantly lower than those in the other two groups: 7 cm3 in the control group and 8.13 cm3 in the moderate group, respectively (P = 0.02). A more significant difference was found when the first 3-cm area of the NCV was evaluated (P = 0.009). Pharmacologic decongestion caused an increase in nasal patency by 54% from the baseline NCV values in the control group, 38% in the moderate group and 48% in the severe group. There was no significant difference among the three groups. Changes in nasal symptoms were also determined by questionnaire. The degree of improvement in subjective nasal congestion was more pronounced in the allergic groups than in the control group.

Acoustics↗

PubMed1998

[A new reconstruction procedure as antireflux surgery after proximal gastrectomy. Interposition of the jejunal pouch with valvuloplasty].

In order to reduce the incidence of reflux esophagitis following proximal gastrectomy, we have developed a new reconstruction procedure with an interposed jejunal pouch with antireflux valvuloplasty between the esophagus and the gastric remnant. After a standard proximal gastrectomy and lymph node dissection, the jejunum is divided at a point 25 cm from the Treitz ligament. The distal jejunum is pulled up through the transverse mesocolon with a mesenterium and anastomosed to the esophagus with a PCEEA stapling device. The pulled through jejunum is doubled up at a point 30 cm from the esophagojejunostomy, and the 5 cm tip of the jejunum is resected. A 5.5 cm autosuture GIA is inserted into the jejunum from both cut ends of the jejunum for side-to-side anastomosis on the antimesenteric side to make a 5 cm long jejunal pouch, and the jejunum is further divided 5 cm distal from the jejunal pouch. As a result, the interposed jejunal segment is omponed of a single-lumen 15 cm jejunum, a parallel lumen 5 cm jejunum, and a double-lumen jejunum. In the double-lumen jejunum, the jejunal pouch plays the role of a pressure absorber in the residual stomach, and the septum of the parallel lumen jejunum that of an anti-reflux valve. Peristalsis of the single lumen 15 cm jejunum prevents reflux to the esophagus. Postoperative examinations showed that this reconstruction method has satisfactory to excellent results.

Adult↗

PubMed1997

Expression of PCNA and p53 in esophageal dysplasia and esophageal carcinoma.

We examined the immunohistochemical expression of proliferating-cell nuclear antigen (PCNA) and p53 proteins in dysplasia and intramucosal carcinoma of the esophagus. Immunohistochemistry was performed with monoclonal antibodies directed against PCNA and p53. We used surgically resected specimens from 29 patients who had a total of 55 lesions of severe dysplasia (n = 16), intraepithelial carcinoma (n = 21), and mucosal carcinoma (n = 18). The mean PCNA index with immunoreactivity for p53 was 48.9 +/- 6.5 in areas of severe dysplasia (n = 7), 58.2 +/- 7.3 in areas of intraepithelial carcinoma (n = 10), and 71.4 +/- 9.3 in the invasive areas of mucosal carcinoma (n = 10). The mean PCNA index without immunoreactivity for p53 was 41.2 +/- 5.5 in areas of severe dysplasia (n = 9), 48.0 +/- 7.4 in areas of intraepithelial carcinoma (n = 11), and 63.7 +/- 9.1 in invasive areas of mucosal carcinoma (n = 8). The PCNA indices of the areas of severe dysplasia with immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma with immunoreactivity for p53. Similarly, the PCNA indices of severe dysplasia without immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma without immunoreactivity for p53. These results thus suggest that severe dysplasia has a lower proliferative potential than carcinoma and may therefore represent a precancerous lesion.

Adult↗

PubMed1997

[A case of chronic expanding hematoma resected 37 years after lobectomy].

A 65-year-old man was admitted for evaluation of slowly growing mass shadow in the right lower lung field on chest X-ray film. He had undergone right upper lobectomy for pulmonary tuberculosis 37 years before. As we could not rule out a suspicion of mediastinal tumor, thracotomy was performed. Histological examination of the resected mass showed a hematoma surrounded by dense fibrotic tissue. And the mass was resultantly diagnosed as chronic expanding hematoma. The mechanism of chronic expanding hematoma is unclear. In our review of the Japanese literatures, only 10 cases including this one, resected more than twenty years after the initial trauma or operation, could be found.

Aged↗

PubMed1997

[Diffuse alveolar hemorrhage associated with idiopathic interstitial pneumonia syndrome after allogeneic bone marrow transplantation].

A 24-year-old male with myelodysplastic syndrome (refractory anemia) was treated with allogeneic bone marrow transplantation (BMT) from HLA-identical brother on September 9, 1994, after conditioning with busulfan and cyclophosphamide. From early in April 1995, the patient complained of cough and fever. Chest X-ray showed interstitial infiltrates involving hilar and lower lung fields. Although pulmonary infiltrates were resolved with methylprednisolone pulse therapy, on May 19, the patient rapidly deteriorated with dyspnea. Diffuse alveolar infiltrates appeared on chest X-ray and he died of respiratory failure. At autopsy, diffuse alveolar hemorrhage accompanied with thickening of the alveolar walls and interstitial infiltration of lymphocytes was demonstrated. There was no evidence of bleeding in other organs. This is a rare case of diffuse alveolar hemorrhage in the late stage of allogeneic BMT. This report should lead to an evaluation of this disease by the collection of similar cases.

Adult↗