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Biomedical subjects

G Tamura

Publications and source records attributed to G Tamura.

At least 55 records · Page 3Linked to original sources
PubMed1999

P53 gene protein overexpression predicts results of trimodality therapy in esophageal cancer patients.

BACKGROUND: P53 protein overexpression in esophageal cancer and its correlation with response and survival after chemoradiation was retrospectively investigated. METHODS: Pretreatment and resection specimens were stained by automatic p53 immunohistochemical staining technique. RESULTS: P53 was expressed in 84.0% of esophagoscopy (EGD) biopsies; 71.4% of patients with metastasis of thoracoscopy/laparoscopy lymph nodes (TS/LS LN) identified by hematoxylin/eosin (H/E) were p53 (+); 14.2% of patients with negative TS/LS LN by H/E were p53 (+). Eleven out of 18 patients with p53 (+) in pretreatment EGD remained p53 (+) after chemoradiation; 38.8% of these patients had a pathological complete response (pCR). The median survival of this group was 15 months. Of 4 patients with p53 (-) pretreatment EGD, all of those were still p53 (-) after chemoradiation; 75% of these patients had pCR. The median survival was 30 months. In patients with p53 (+) TS/LS LN, 23% had a pCR after chemoradiation with a median survival of 16 months. In patients with p53 (-) TS/LS LN, 50.0% had a pCR with a median survival of 31.5 months. CONCLUSIONS: P53 protein overexpression in pretreatment EGD and TS/LS LN may predict response to chemoradiation and survival in esophageal cancer patients.

Adenocarcinoma↗
PubMed1999

Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach.

We describe extremely well-differentiated intestinal-type adenocarcinomas of the stomach which mimic complete-type intestinal metaplasia. It is often difficult to discriminate such neoplastic lesions from inflamed or regenerative changes of intestinal metaplasia histologically. The aim of this study was to elucidate the clinicopathologic features of this unique carcinoma. Eight cases of gastric carcinoma of this type that were invasive beyond the muscularis mucosae were selected for mucin histochemical and immunohistochemical analyses. The carcinomas showed the following features: (1) predominant cells that had differentiated to mature neoplastic cells, with features of small intestinal absorptive cells (complete-type intestinal metaplastic cells), which have sialomucin, MUC2-positive cells, and brush border features detected by CD10 (56C6) staining; (2) neoplastic tubules in the mucosa showing branching, tortuous, anastomosing, and plexiform structures, which were more pathognomonic than the cytological features; (3) lesions distributed predominantly in the middle third of the stomach and surrounded by the fundic mucosa; and (4) zonal distribution of Ki-67-positive proliferative cells like those of intestinal metaplasia in the lower third to half of the cancerous tubules in the mucosa. The lesions consisted mainly of illusory carcinoma; however, there were foci of pathognomonic elements in some areas of the tumors. Several biopsy samplings of the lesion would ensure the histopathologic diagnosis. This unique lesion forms a subgroup of intestinal-type carcinomas of the stomach and is suggested to have a close link with complete-type intestinal metaplasia, previously ignored as a precancerous lesion.

Adenocarcinoma↗
PubMed1999

Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist.

BACKGROUND: The etiology and treatment of premenstrual exacerbations of asthma (PMA) remain uncertain. OBJECTIVE: We investigated the role of cellular mediators released from inflammatory cells in the airflow limitation during PMA. METHODS: Serum levels of leukotriene (LT) B(4), LTC(4), platelet- activating factor, histamine, IL-1beta, IL-4, IL-5, IL-6, and GM-CSF were measured at different time points, first just before or during menstruation when the peak expiratory flow rate (PEFR) began to decrease precipitously and second during the menstrual midcycle week (days 10-16) when the PEFR returned to baseline values in patients with PMA and in age-matched asthma patients without PMA at the same intervals. RESULTS: Serum levels of LTC(4) were significantly higher during exacerbations of asthma than after recovery (69.0 +/- 16.0 pg/mL vs 24.0 +/- 9.5 pg/mL, P <.05), whereas those of IL-1beta, IL-4, IL-5, IL-6, GM-CSF, histamine, LTB(4), and platelet-activating factor did not differ between 2 periods in 5 patients with PMA. In contrast, in 5 asthmatic patients without PMA serum levels of cellular mediators did not differ between corresponding periods. Oral administration of pranlukast, an LT receptor antagonist (225 mg twice daily), significantly reduced decreases in PEFR from the baseline values (110 +/- 21 L/min with pranlukast vs 233 +/- 20 L/min without pranlukast, P <.01) in association with an improvement of asthma symptom scores (6.5 +/- 1. 1 with pranlukast vs 9.8 +/- 0.7 without pranlukast, P <0.05) in 5 patients with PMA. CONCLUSION: LTs are partly involved in the pathogenesis of PMA, and LT receptor antagonists may be useful for preventing airflow obstruction in patients with PMA.

Adolescent↗
PubMed1999

Mutations in mitochondrial control region DNA in gastric tumours of Japanese patients.

The non-coding control region of mitochondrial DNA (mtDNA), containing the hypervariable regions HV1 and HV2 and the D-loop region, was screened for mutations in 45 gastric tumours (15 tumours each of adenoma, differentiated adenocarcinoma and undifferentiated carcinoma). We found mutations in two of the 45 tumours (4%); a 1 bp A deletion at nucleotide position 248 in a differentiated adenocarcinoma and a G to A transition at nucleotide position 16,129 in an adenoma. We also observed 10 polymorphisms, four of which were not previously recorded. Both mtDNA mutations were present in replication error negative (RER-) tumours. Short mono- or dinucleotide repeats in the control region, such as (C)7, (A)5 or (CA)5, were not altered regardless of nuclear genetic instability. In summary, mtDNA is mutated in a subset of benign and malignant gastric tumours, but, disruption of the mtDNA repair system appears not to be significantly involved in gastric tumours of Japanese patients.

DNA Repair↗
PubMed1999

Esophageal adenocarcinoma that probably originated in the esophageal gland duct: a case report.

A case of primary esophageal adenocarcinoma in a 64-year-old man is reported. An ulcerating tumor was located in the middle intrathoracic esophagus. Histopathological examination revealed a moderately differentiated adenocarcinoma, which had invaded down to the adventitia. The cancerous tubuli were lined by flattened cuboidal cells with eosinophilic cytoplasm, which were analogous with the esophageal gland ducts and syringoma of the skin. The carcinoma was spread widely in the lamina propria mucosae without intraepithelial neoplastic elements. An immunohistochemical profile of individual cytokeratins and other epithelial markers in the carcinoma was similar to that of the esophageal gland ducts. Barrett's metaplastic epithelium or ectopic gastric mucosa was not found around the tumor. It is strongly suggested that this unique carcinoma is derived from the esophageal gland ducts.

Adenocarcinoma↗
PubMed1999

Multiple pulmonary leiomyomatous hamartoma with secondary ossification.

A 31-year-old woman presented with multiple pulmonary leiomyomatous hamartoma (MPLH) with secondary ossification. She had a past history of parosteal osteosarcoma. The pulmonary lesions were composed of spindle-shaped cells arranged in interlacing fascicles, among which glands or duct-like spaces were scattered. As some lesions contained bony tissues, it was unclear whether or not the pulmonary lesions were metastases of parosteal osteosarcoma. However, the majority of spindle-shaped cells were positive for alpha-smooth muscle actin, including cells proliferating around the bony tissues. Clonality analysis using a target of human androgen receptor (HUMARA) gene disclosed that the pulmonary nodules were polyclonal. These findings do not indicate that the lesions were metastatic. We would like to emphasize that MPLH can show osseous metaplasia.

Adult↗
PubMed1999

Ameloblastoma with basal cell carcinoma-like feature emerging as a nasal polyp.

A case of a 63-year-old man with ameloblastoma with basal cell carcinoma (BCC)-like features clinically emerging as a nasal polyp is reported. The left nasal cavity was filled with a solid mass, which seemed to be a sinusitis-associated nasal polyp. The polyp was covered by parakeratotic squamous epithelium which was directly connected to the BCC-like tumor nest. The BCC-like features gradually changed to adamantinoid features. The polyp was connected with a huge mass filling the maxillary sinus and the molar area, which consisted of conventional ameloblastoma features. Although the tumor was finally diagnosed as an ameloblastoma of the maxilla, the biopsy specimen forced us to face the problem of differential diagnosis, ameloblastoma with BCC-like features or adamantinoid basal cell carcinoma (BCC). Immunohistochemical examination revealed that tumor cells of the ameloblastoma reacted with anticytokeratin antibody KL-1 but not with antiepithelial antibody Ber-EP4, and these reaction patterns were completely contrary to those of BCC. It is emphasized that immunohistochemical examination using anticytokeratin antibody KL-1 and antiepithelial antibody Ber-EP4 is a good tool for distinguishing ameloblastoma with BCC-like features from adamantinoid BCC.

Ameloblastoma↗
PubMed1999

Mucinous carcinoma of the breast: a multifaceted study with special reference to histogenesis and neuroendocrine differentiation.

Although mucinous carcinoma (MC) of the breast is considered to originate from ductal carcinoma, it is not known whether mucinous growth begins in the intraductal carcinoma or later in the invasive carcinoma. In this study, 33 MC (16 pure without any ductal components, 10 mixed Type I with an intraductal component, seven mixed Type II with a common invasive ductal carcinoma (IDC) component)) were examined to clarify the time when mucinous growth begins. Histochemical and immunohistochemical examinations of mucin revealed that mucinous growth can begin in the intraductal carcinoma and in the common IDC. Histological transition and clonality analysis using microsatellite markers supported that some MC originate from common IDC. The pure type of MC probably originates from the intraductal carcinoma, showing a micropapillary feature. Neuroendocrine differentiation, known to be associated with MC, seemed to create the main progress in the typical MC. Moreover, we analyzed the factors of a worse prognosis of mixed MC Type II, which was strongly suggested by the lymph node status. However, no explainable differences on the cell proliferating ability, or c-erbB-2 and p53 protein overexpression were found.

Adenocarcinoma, Mucinous↗
PubMed1999

Suplatast tosilate inhibits late response and airway inflammation in sensitized guinea pigs.

The effect of suplatast tosilate, which has been proven to inhibit T-cell synthesis of IL-4 and IL-5, on the response to antigen inhalation challenge was investigated in sensitized guinea pigs. The animals were given an oral dose of 30 or 100 mg/kg of suplatast or vehicle (distilled water) daily for 1 wk before antigen challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage and lung fixation. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils and lymphocytes in the airways. After 1 wk of treatment with the high dose of suplatast, the late asthmatic response and the recruitment of eosinophils and lymphocytes into the airways were significantly inhibited, but the early asthmatic response was not affected. In situ hybridization revealed that challenge-induced increases in IL-5 mRNA-positive cells in lung tissue were significantly inhibited after treatment. Thus, suplatast inhibited airway obstruction in the late phase by specifically inhibiting the inflammatory process after mast cell degranulation.

Airway Resistance↗
PubMed1999

Ovalbumin (OVA) and Mycobacterium tuberculosis bacilli cooperatively polarize anti-OVA T-helper (Th) cells toward a Th1-dominant phenotype and ameliorate murine tracheal eosinophilia.

A recent increase in allergic disorders has coincided with a decrease in infections, including tuberculosis. Although an inverse association between tuberculin responses and atopic disorders was reported, it was not known how T-helper (Th)1-biased immune responses to Mycobacterium tuberculosis influenced Th2-dominant responses to allergens. We examined whether M. tuberculosis could modulate ovalbumin (OVA)-induced eosinophilic inflammation in the murine trachea in a manner that transcended the barrier of antigen specificity. We found that CD4(+) T cells primed with OVA in complete Freund's adjuvant (CFA) inhibited OVA-induced tracheal eosinophilia through interferon (IFN)-gamma secretion. Immunization with an irrelevant antigen in CFA or with OVA in incomplete Freund's adjuvant failed to induce suppressor cells. In vitro experiments confirmed that both M. tuberculosis and OVA (as opposed to either one alone) were necessary to evoke polarized development toward a Th1-like phenotype through interleukin-12 secretion. These results indicate that exposure to an allergen along with M. tuberculosis switches development of allergen-specific T cells toward a Th1 phenotype, which, in turn, downregulates allergic manifestations in an antigen-specific manner. The possible implications of these results are discussed in the context of the causal relationship between a decrease in tuberculosis and an increase in allergic disorders.

Animals↗
PubMed1999

Transforming growth factor-beta secreted from CD4(+) T cells ameliorates antigen-induced eosinophilic inflammation. A novel high-dose tolerance in the trachea.

The induction of peripheral tolerance is one of the feasible approaches for the control of autoimmunities and allergies. Tolerance induction in the intestine has been studied extensively and therapeutic applications to autoimmunities are in progress, whereas tolerance in the respiratory tract is poorly investigated. We examined the immunoregulatory mechanisms for evading exaggerated inflammatory responses in the murine airway mucosa. Administration of an optimal dose of ovalbumin (OVA) to the trachea elicited eosinophilic inflammation in the trachea of OVA/aluminum hydroxide-sensitized BALB/c mice, whereas higher doses were unable to do so. This failure paralleled the downregulation of interleukin-4 production by mediastinal lymph node (LN) T cells. This high-dose tolerance was attributable to the mechanisms of antigen (Ag)-specific suppression, because the adoptive transfer of CD4(+) LN T cells from the OVA-tolerant mice inhibited the OVA-specific, but not irrelevant Ag KLH-specific, eosinophilic responses. The inhibitory effects were neutralized by the intratracheal administration of anti-transforming growth factor (TGF)-beta, but not that of anti-interferon (IFN)-gamma, monoclonal antibodies, indicating that the high-dose tolerance was mediated by secreted TGF-beta, but not by the dominance of transferred T helper (Th)1 cells over Th2 cells. The pivotal role of TGF-beta was reinforced by the finding that the LN cells from the OVA-tolerant mice produced TGF-beta in response to the in vitro Ag stimulation. These results demonstrate a novel regulatory mechanism in the airway: that TGF-beta secreted by T cells plays an important role in the downmodulation of the immune responses to high doses of Ag which might otherwise induce deleterious inflammation in the airway mucosal tissues.

Animals↗
PubMed1999

Endoscopic sinus surgery improves pulmonary function in patients with asthma associated with chronic sinusitis.

We evaluated the clinical efficacy of endonasal endoscopic sinus surgery (ESS) in patients with asthma associated with chronic sinusitis. Twenty-one patients (13 men and 8 women) from 27 to 72 years old were enrolled in this study. All patients had had sinus-related symptoms for more than 3 months and had computed tomographic evidence of paranasal sinus opacification. Fifteen patients underwent bilateral endonasal ESS under local anesthesia, and 6 other patients without surgery were controls. The sinus-related symptoms of the preoperative and postoperative periods were assessed via a questionnaire. The period 6 months prior to surgery was compared with that 6 months postoperatively with regard to peak expiratory flow and total dosage of systemic glucocorticoids. Sinus-related symptoms in the ESS group were significantly improved 6 months postoperatively. The average peak expiratory flow 6 months following surgery was improved in the ESS patients, ranging from 40 to 190 L/min. Seven patients showed a reduction in the need for corticosteroids, whereas 2 patients were unchanged and 2 patients required larger dosages. The remaining 4 patients needed no corticosteroids before or after ESS. No significant changes in sinus-related symptoms or peak expiratory flow were obtained for the control group. Improvement of paranasal sinus disease by successful ESS can alleviate pulmonary dysfunction in asthma associated with chronic sinusitis. We believe that adequate and positive treatment for chronic sinusitis would reduce not only the nasal and sinus-related symptoms evoked by chronic sinusitis, but also some of the signs induced by asthma.

Adult↗
PubMed1999

Insertion analysis of putative functional elements in the promoter region of the Aspergillus oryzae Taka-amylase A gene (amyB) using a heterologous Aspergillus nidulans amdS-lacZ fusion gene system.

Expression of the Taka-amylase A gene (amyB) of Aspergillus oryzae is induced by starch or maltose. The A. oryzae amyB gene promoter contains three highly conserved sequences, designated Regions I, II, and III, compared with promoter regions of the A. oryzae glaA encoding glucoamylase and the agdA encoding alpha-glucosidase. To identify the function of these sequences within the amyB promoter, various fragments containing conserved sequences in the amyB promoter were introduced into the upstream region of the heterologous A. nidulans amdS gene (encoding acetamidase) fused to the Escherichia coli lacZ gene as a reporter. Introduction of the sequence between -290 to -233 (the number indicates the distance in base pairs from the translation initiation point (+1)) containing Region III significantly increased the expression of the lacZ reporter gene in the presence of maltose. The sequence between -377 to -290 containing Region I also increased the lacZ activity, but its maltose inducibility was less than that of Region III. The sequence between -233 to -181 containing Region II had no effect on the expression. These results indicated that Region III is most likely involved in the maltose induction of the amyB gene expression.

Amidohydrolases↗
PubMed1999

[Comparison of CRH test and ACTH test in patients with bronchial asthma].

Although glucocorticoid is the most effective agent for bronchial asthma, its systemic administration leads to suppression of adrenocortical function. Rapid ACTH test has been performed for assessing the function of the hypothalamic-pituitary-adrenocortical (HPA) system of asthmatics. Recently human corticotropin-releasing hormone (CRH) has been chemically synthesized. In order to evaluate clinical usefulness of CRH, we compared CRH test with ACTH test in 17 patients with bronchial asthma (3 patients out of them concurrently receiving prednisolone 5-10 mg/day). Both tests were carried out within 2 weeks after 6 month treatment with fluticasone propionate (800 micrograms/day) inhaled via pMDI. There is no significant difference between results obtained from the both tests. Thus, dividing subjects into high and low responders based on an extent of increases in plasma ACTH levels after the CRH injection, we found a significant difference in maximal plasma concentrations of cortisol between after CRH and ACTH injections in the low responders. Therefore, in some patients, CRH test provides more accurate assessment of the function of HPA system than ACTH test.

Adrenocorticotropic Hormone↗
PubMed1999

[Effects of an ATP-sensitive K+ channel activator, JTV-506, on antigen-induced early and late asthmatic responses in sensitized guinea pigs].

Effects of an ATP-sensitive K+ channel activator, JTV-506, on dual asthmatic responses and airway inflammation after antigen inhalation challenge were investigated in asthma model of guinea pigs. The animals were given an oral dose of 1 mg/kg of JTV-506 or vehicle (0.5% carboxymethyl cellulose sodium) 1 hour before and 3 hours after antigen inhalation challenge. Measurement of pulmonary resistance for 6 h was followed by bronchoalveolar lavage. After antigen challenge, all guinea pigs in the vehicle group displayed dual-phase airway obstruction and accumulation of eosinophils in the airways. After the treatment with JTV-506, the early asthmatic response was significantly inhibited, although the late asthmatic response or the recruitment of eosinophils into the airways were not inhibited. Therefore, we suggested that JTV-506 may inhibit airway smooth contraction induced by chemical mediators, but not function of CD4+ T lymphocytes.

Airway Resistance↗
PubMed1998

Functionally inactivating point mutation in the tumor-suppressor IRF-1 gene identified in human gastric cancer.

Loss of heterozygosity (LOH) observed in human tumors strongly suggests the existence of (a) tumor-suppressor gene(s) at the concerned locus. A series of studies has revealed that LOH on the long arm of chromosome 5 (5q) frequently occurs in differentiated gastric adenocarcinomas. Furthermore, it has been shown that the interferon regulatory factor-1 (IRF-1) locus on chromosome 5q31.1 is one of the common minimal regions of LOH in these cancers. IRF-1 is a transcriptional activator that shows tumor-suppressor activity in the mouse. In the present study, we examined the sequence of the IRF-1 gene in 9 cases of histologically differentiated gastric adenocarcinomas, all of which exhibited LOH at the IRF-1 locus. We identified a mis-sense mutation in the residual allele in one case. This mutated form of IRF-1 showed markedly reduced transcriptional activity. In addition, overexpression of wild-type IRF-1 induced cell-cycle arrest, whereas such activity was attenuated in the mutant IRF-1. These results suggest that the loss of functional IRF-1 is critical for the development of human gastric cancers.

3T3 Cells↗
PubMed1998

Tissue-specific involvement of multiple mitochondrial DNA deletions in familial mitochondrial myopathy.

It is still uncertain how deleted mitochondrial DNA (mtDNA) is distributed to each tissue during development, although deletions of mtDNA have been extensively observed in various pathologic conditions. This paper presents two Japanese siblings with progressive external ophthalmoplegia exhibiting multiple mtDNA deletions. In one patient, similar multiple mtDNA deletions were found in skeletal muscle specimens as well as in the spinal cord but not in the myocardium, liver or leukocytes. A similar deletion pattern was found in the skeletal muscle but not in the leukocytes of the other patient. The results suggest the complex mechanism to generate, expand and eliminate the deleted mtDNA in humans.

Adult↗