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Biomedical subjects

N Dobashi

Publications and source records attributed to N Dobashi.

At least 19 recordsLinked to original sources
PubMed1999

Expression of cytokeratin 19 mRNA in human lung cancer cell lines.

The present study was designed to clarify the mechanism by which some lung cancer cell lines can produce cytokeratin 19 (CK19) fragment and others cannot. We hypothesized that some lung cancer cell lines which cannot release CK19 express an incomplete sequence of CK19 mRNA. Expression of mRNA was evaluated by RT-PCR using several primer pairs for CK19. CK19 in the culture supernatant was measured by an immuno-radiometric assay. CK19 protein synthesis was evaluated by Western immunoblot and immunohistochemistry. Among 16 lung cancer cell lines, 7 released significant amounts of CK19 in the supernatant. In some cell lines, expression of CK19 mRNA was observed only in some combinations of primers, suggesting that incomplete mRNA was expressed. 3'-RACE analysis detected amplified products of a shorter size compared with normal amplified products in cell lines which expressed incomplete CK19 mRNA, suggesting that 3'-ends of mRNA for CK19 were deleted. Results of Western immunoblot and immuno-histochemical staining using anti-human CK19 monoclonal antibody completely correlated with the results on CK19 levels in culture supernatants as well as with complete expression of mRNA. We conclude that levels of CK19 closely relate to the expression of complete mRNA for CK19.

Adenocarcinoma↗
PubMed1999

Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders.

It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis.

Adult↗
PubMed1999

Elevated serum and BAL cytokeratin 19 fragment in pulmonary fibrosis and acute interstitial pneumonia.

Cytokeratin 19 fragment (CK19) levels in serum have already been documented as a useful tumour marker for lung cancer. In the present study, it was hypothesized that CK19 may be increased in the serum and epithelial lining fluid of the respiratory tract from patients with pulmonary fibrosis. CK19 was measured in the serum and bronchoalveolar lavage fluid (BALF) of patients with pulmonary fibrosis and the correlation between CK19 levels and clinical parameters evaluated. Nineteen patients diagnosed with idiopathic pulmonary fibrosis (IPF), eight with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD), seven patients with acute interstitial pneumonia (AIP), and 10 normal smokers as a control group were studied. CK19 levels in sera of patients with IPF and patients with PF-CVD were significantly increased compared to those of normal smokers. CK19 levels in sera of patients with AIP were significantly increased compared to those of other groups. CK19 values in the BALF of patients with pulmonary fibrosis were significantly elevated compared to those of normal smokers. CK19 values in sera charged according to the progression or improvement of the acute lung injury. Immunohistochemical study using pulmonary tissues obtained from patients with AIP demonstrated that the hyaline membrane and proliferating type II pneumocytes were stained by anti-human cytokeratin 19 antibody. These data demonstrated that the measurement of cytokeratin 19 fragment is a useful parameter to evaluate the activity of lung epithelial cell damage and repair.

Acute Disease↗
PubMed1999

Detection of large molecular weight cytokeratin 8 as carrier protein of CA19-9 in non-small-cell lung cancer cell lines.

It has been reported that cytokeratin 8 (CK8) is expressed in all non-small-cell lung cancers (NSCLC). We hypothesized that antigenic changes of CK8 may occur in some NSCLC cell lines. To prove this, Western immunoblot analysis using anti-human CK8 monoclonal antibodies as well as immunohistological staining of CK8 were performed in NSCLC cell lines. As a result, CK8 which had a higher molecular weight than recombinant CK8 was demonstrated in two of eight NSCLC cell lines. In addition, this CK8 contained antigenic epitopes of CA19-9. This CK8 with higher molecular weight, may have played a role in the process of invasion or metastasis of NSCLC.

Adenocarcinoma↗
PubMed1999

Detection of anti-ADAM 10 antibody in serum of a patient with pulmonary fibrosis associated with dermatomyositis.

OBJECTIVES: It has been suggested that the humoral immune system plays a part in the pathogenesis of pulmonary fibrosis. Although circulating autoantibodies to lung protein(s) have been suggested, few lung proteins have been characterised. The purpose of this study is to determine the antigen recognised by serum of a patient with pulmonary fibrosis associated with dermatomyositis. METHODS: To accomplish this, anti-small airway epithelial cell (SAEC) antibody in a patient's serum was evaluated using a western immunoblot. RESULTS: An autoantibody against SAEC was found, and the antigen had a molecular weight of 62 kDa. Using the patient's serum, clones from the normal lung cDNA library were screened and demonstrated that anti-SAEC antibody in the patient's serum was against ADAM (A disintegrin and metalloprotease) 10. CONCLUSION: This is the first report that demonstrates the existence of anti-ADAM 10 antibody in a patient with pulmonary fibrosis associated with dermatomyositis.

ADAM Proteins↗
PubMed1999

Pathological and radiological changes in resected lung specimens in Mycobacterium avium intracellulare complex disease.

The present study was designed to evaluate the pathological and immunohistochemical findings of Mycobacterium avium intracellulare complex (MAC) lung infection. A retrospective study was performed in five cases with positive cultures for MAC in whom lung resections were performed between January 1989 and December 1996. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria defined by the American Thoracic Society. In addition, MAC was cultured from all of the five lung specimens. Pathological and immunohistochemical findings as well as chest computed tomography (CT) findings were evaluated in these five patients. Pathological findings of bronchiectasis, bronchiolitis, centrilobular lesion, consolidation, cavity wall and nodules were demonstrated, respectively, in relation to chest CT findings. Extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; 2) myofibroblasts extensively infiltrating the cavity wall; and 3) B-cells detected in aggregates in the vicinity of the epithelioid granulomas. This study identified pathological and immunohistochemical characteristics of Mycobacterium avium complex infection relative to chest computed tomography findings and allowed the conclusion that bronchiectasis and bronchiolitis were definitely caused by Mycobacterium avium complex infection.

Adult↗
PubMed1999

[Acute vincristine neurotoxicity in a non-Hodgkin's lymphoma patient with Charcot-Marie-Tooth disease].

A 44-year-old, previously healthy man with a diagnosis of non-Hodgkin's lymphoma (NHL, diffuse large B-cell type, stage IIA) was treated with combination chemotherapy including vincristine (VCR). After receiving a cumulative dose of VCR, he experienced rapid and marked weakening which progressed to quadriplegia and bulbar palsy. Prior to this therapy, the patient had no neurological problems, and his siblings were asymptomatic. Physical examination identified pes cavus (hollow foot), and electrodiagnostic studies showed markedly slower nerve conduction velocity of myelinated fibers, with abundant "onion bulb" formations. Chromosomal analysis detected 17p11.2-12 duplication, thus yielding a diagnosis of Charcot-Marie-Tooth (CMT) 1A. CMT disease is a familial neuromuscular disorder, and the incidence is approximately 1 in 2,500. We concluded that if CMT disease is diagnosed, vincristine should be avoided due to the potential severity of neurotoxicity to small doses.

Adult↗
PubMed1999

Elevation of cytokeratin 19 fragment in patients with interstitial pneumonia associated with polymyositis/dermatomyositis.

OBJECTIVE: Cytokeratin 19 fragment (CK19) levels in serum have been documented as a useful tumor marker for lung cancer. We hypothesize that CK19 may increase in serum in patients with interstitial pneumonia associated with polymyositis/dermatomyositis (PM/DM) and CK19 might be a useful variable to evaluate the activity of lung injury. METHODS: 1. We measured CK19 in sera in 15 patients diagnosed with PM/DM; 6 had nonspecific interstitial pneumonia (NIP), 4 had acute interstitial pneumonia (AIP), and 5 had no pulmonary involvement. We also measured CK19 in 10 healthy nonsmokers serving as a control group. 2. We evaluated the correlation between CK19 level and individual clinical course in patients with pulmonary involvement associated with PM/DM. RESULTS: CK19 levels in sera of patients with NIP associated with PM/DM were significantly higher versus patients with PM/DM without interstitial pneumonia and healthy nonsmokers. CK19 levels in sera in patients with AIP associated with PM/DM were significantly higher compared with the other groups. CK19 values in sera changed according to the progression or improvement of interstitial pneumonia. Immunohistochemical studies using pulmonary tissues obtained at autopsy from patients with AIP associated with PM/DM revealed that the hyaline membrane was mostly stained by anti-human cytokeratin 19 monoclonal antibody as well as the strong positivity of proliferating type II pneumocytes. CONCLUSION: These results suggest that the measurement of CK19 was a useful variable to evaluate the activity of lung injury in interstitial pneumonia associated with PM/DM.

Adult↗
PubMed1998

Detection of anti-cytokeratin 8 antibody in the serum of patients with cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen vascular disorders.

BACKGROUND: It has been suggested that the humoral immune system plays a role in the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating autoantibodies to lung protein(s) have been suggested, none of the lung proteins have been characterised. The purpose of this study was to determine the antigen to which the serum from patients with pulmonary fibrosis reacted. METHODS: The anti-A549 cell antibody was characterised in a patient with CFA using Western immunoblotting and immunohistochemical staining of A549 cells. As we identified that one of the antibodies against A549 cells was anti-cytokeratin 8, the expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we attempted to establish an enzyme linked immunosorbent assay to measure the levels of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). RESULTS: Initially two anti-A549 cell antibodies were detected in the serum of patients with pulmonary fibrosis, one of which was characterised as anticytokeratin 8 antibody by Western immunoblotting. We were able to establish an ELISA to measure anti-cytokeratin 8 antibody and found significantly higher levels in patients with CFA and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and pulmonary emphysema. CONCLUSIONS: One of the anti-A549 cell antibodies in the serum of patients with CFA was against cytokeratin 8. The serum levels of anti-cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These results suggest that anticytokeratin 8 antibody may be involved in the process of lung injury in pulmonary fibrosis.

Adult↗
PubMed1998

Role of daunorubicin in the induction therapy for adult acute myeloid leukemia.

PURPOSE: To evaluate the relationship of total-dose of daunorubicin (DNR) to the induction therapy and treatment outcome, we have administered individualized doses of DNR during induction treatment to patients with acute myelogenous leukemia (AML). PATIENTS AND METHODS: Ninety-two previously untreated adult patients with AML who entered our hospital were analyzed for the dose of DNR required to achieve complete remission (CR), the CR rate, disease-free survival (DFS), and overall survival (OS). Induction therapy consisted of DNR 40 mg/m2 daily intravenously from day 1 until the marrow was hypoplastic, cytarabine (Ara-C), prednisolone (PRD), and/or 6-thioguanine (6-TG). RESULTS: Eighty-three of 92 patients with adult AML were assessable for this study. Sixty-three (76%) patients achieved CR. Fifty-two of 63 CR patients achieved the CR in the first course of induction therapy, and 11 patients required the second course of induction therapy. The 5-year and 10-year DFS rates were 31.2% and 5-year and 10-year OS rates were 45.1% and 42.3%, respectively. The median total dose of DNR in the induction therapy was 280 mg/m2 (120 to 480 mg/m2). DNR dose did not influence the response to therapy and was not influenced by the initial WBC count or French-American-British (FAB) system classification. CONCLUSION: These results indicated that when the dose was linked to observed tumor response, the optimal dose of DNR in the induction therapy was approximately 280 mg/m2 (40 mg/m2 for 7 days), which is greater than the conventional dose of 40 to 60 mg/m2 for 3 days.

Adolescent↗
PubMed1998

[EPOCH therapy for relapsed/refractory lymphoid malignancies].

Patients with refractory or relapsed non-Hodgkin's lymphoma (NHL), acute T-cell leukemia (ATL), ATL lymphoma and acute lymphocytic leukemia (ALL) received EPOCH therapy. All were previously treated with doxorubicin (DOX), vincristine (VCR) and other drugs. The EPOCH treatment schedule is consisted with DOX (10 mg/M2/day, 5 days c.i.v.), VCR (0.4 mg/M2/day, 4 days c.i.v.), etoposide (50 mg/M2/day, 4 days c.i.v.), cyclophosphamide (750 mg/M2/day, day 6 i.v.) and prednisolone (60 mg/M2/day, 5 days p.o.). Twenty-one patients (ALL:10, NHL:8, ATLL:2, ATL:1) were assessable for response and toxicity. Two patients with ALL and NHL, respectively, achieved a complete remission and 3 patients obtained partial remission (NHL:2, ATLL:1). The hematological toxicity (grade > 1) included neutoropenia, anemia and thrombocytopenia, which were observed in 83.3%, 76.7% and 76.7% respectively, of total 30 EPOCH courses. The major non-hematological toxicities were nausea/vomiting, constipation and infection, but most of the toxicity were tolerable with sufficient clinical supportive care. These results indicate that continuous infusion of DOX, VCR and ETP might be effective in patients who were treated with, and presumed to be resistant to the same drugs administrated by bolus infusion.

Adolescent↗
PubMed1998

[Primary cardiac non-Hodgkin's lymphoma].

A 69-year-old man who initially presented with lumbago developed heart failure during an MRI scan on the day of admission. A chest X-ray showed cardiomegaly and bilateral pleural effusion. Echocardiogram and computed tomography (CT) scan of the chest revealed a large tumor mass encompassing the heart with much pericardial effusion was demonstrated. The cytology of the effusion obtained by pericardiocentesis was consistent with non-Hodgkin's lymphoma, diffuse large B cell type. As CT scans of the abdomen and pelvis were negative, he was considered to have primary cardiac lymphoma. Although he responded remarkably to therapy with vincristine, cyclophosphamide and prednisolone and, he developed acute respiratory failure on the seventh month after admission. Although incidence of primary cardiac lymphoma is very low, it is necessary to investigate the mechanism of this disease in order to establish appropriate diagnostic and therapeutic approaches.

Aged↗
PubMed1998

[Prognostic significance of CD7 expression in adult acute myeloid leukemia].

To evaluate the prognostic significance of CD7 expression in de novo acute myeloid leukemia (AML), we studied 63 patients with AML who had been admitted to our hospital between September 1989 and January 1996. Even of the patients were later eliminated from the study (9 due to insufficient surface marker analyses, and 2 due to early death). The remaining 52 patients (median age: 42.5 years) were evaluated for morphologic subtype, immunophenotypic classification, complete remission (CR), disease-free survival (DFS) and overall survival (OS). All 52 patients were grouped by the French-American-British classification system: 10 as M1, 16 as M2, 11 as M3, 8 as M4, 5 as M5, and 2 as M6. Ten of the patients expressed CD7 on their leukemia cells (positive rate > or = 25) and were classified as CD7(+)AML, with morphological subtypes as follows: 3 as M1, 6 as M2, and 1 as M3. Thirty-three of the 42 patients with CD7 + AML (78.6%) and 6 of the 10 patients with CD7 + AML (40%) achieved CR. DFS and OS rates for the patients with CD7(+)AML were 22.1% and 35.4%, respectively; those for the CD7(+)AML patients were 53.3% and 44.4%, respectively. No significant differences in gender hematological findings, clinical manifestations such as hepatosplenomegaly, lymphadenopathy, or incidence of central nervous system involvement, CR rate, and DFS distinguished patients with CD7(+)AML from those with CD7(+)AML. These suggest that CD7 expression is unlikely to be a prognostic factor in AML.

Adolescent↗