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Biomedical subjects

E Takeuchi

Publications and source records attributed to E Takeuchi.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vascular endothelial growth factor in malignant pleural effusion associated with lung cancer.

The presence of vascular endothelial growth factor (VEGF) was examined by enzyme immunoassay in 60 cytology-documented malignant pleural effusions associated with primary lung cancer and 51 other benign and malignant pleural effusions. Exudative pleural effusions contained significantly higher amounts of VEGF than transudative pleural effusions. Among exudative pleural effusions, levels of VEGF in malignant pleural effusions associated with lung cancer were significantly higher than those of benign exudative pleural effusions. There was no significant difference in pleural VEGF in patients with different histological types or clinical stages of lung cancer. Serial measurement of pleural VEGF levels was performed in six lung cancer patients treated with intrapleural instillation of recombinant interferon gamma, and reduction of pleural effusion was associated with decreasing pleural VEGF levels. These findings suggest that VEGF has a role in the accumulation of exudative pleural effusions, especially that of malignant pleural effusion associated with lung cancer.

Adenocarcinoma↗
PubMed1999

Differential activation by cytokines of mitogen-activated protein kinases in bovine temporomandibular-joint disc cells.

Temporomandibular disorders affect a significant proportion of the population. While their aetiology is not well defined, recent histological studies suggest that the majority are similar to the osteoarthritis seen in other joints. Inflammatory cytokines such as interleukin-1 and tumour necrosis factor-alpha appear to be important in the cascade of events leading to joint destruction in osteoarthritis. Here, cells from the disc of bovine temporomandibular joint were used to examine the response to various cytokines in vitro. Disc cells were stimulated with interleukin-1alpha, tumour necrosis factor-alpha, transforming growth factor-beta, platelet-derived growth factor, and basic fibroblast growth factor. Their effects were monitored by assessing the phosphorylation of selected signal-transduction intermediates using western blot. Mitogen-activated protein kinases (Erk 1, Erk 2) were rapidly phosphorylated by exposure to basic fibroblast growth factor, platelet-derived growth factor, and tumour necrosis factor-alpha, while interleukin-1alpha showed a weak response. Transforming growth factor-beta failed to activate these kinases. Examination of the effect of these cytokines on p38 (an intermediate in the stress-activated protein-kinase pathway) showed an increase in phosphorylated p38 when stimulated with tumour necrosis factor-alpha and interleukin-1alpha. The amounts of phosphorylated signal transducer and activator of transcription-3 did not significantly increase when the cells were exposed to any of the cytokines.

Animals↗
PubMed1999

Active form of human hepatocyte growth factor is excreted into bile after hepatobiliary resection.

BACKGROUND/AIMS: We have shown that hepatocyte growth factor is excreted into bile after hepatectomy in patients with biliary tract carcinoma. However, it is not certain whether hepatocyte growth factor in bile is an active molecule or degradation products. METHODS: Bile was obtained from five patients after hepatobiliary resection. Bile hepatocyte growth factor was purified on a heparin-Sepharose column and subjected to Western blotting. It was also tested for growth-stimulating activity with rat primary cultured hepatocytes. Biles from 50 patients who underwent various types of hepatobiliary resections were examined with respect to hepatocyte growth factor by an enzyme-linked immunosorbent assay. RESULTS: Upon Western blotting following nonreducing electrophoresis, the purified bile hepatocyte growth factor showed an 85 kDa peptide corresponding to native hepatocyte growth factor. Under reducing conditions, it showed bands of a-subunit at 69 kDa and beta-subunit at 34 kDa with corresponding monoclonal antibodies. The purified bile hepatocyte growth factor stimulated the [3H]thymidine incorporation into primary cultured hepatocytes with a specific activity comparable to recombinant human hepatocyte growth factor. It was observed that the levels of bile hepatocyte growth factor increased after the various types of hepatobiliary resections, including bile duct resection without hepatectomy. CONCLUSIONS: The human bile obtained after hepatobiliary resection contains active hepatocyte growth factor that can stimulate hepatocyte growth. Bile hepatocyte growth factor increased not only in hepatectomy but in bile duct resection. These results suggest that the biliary tract system may play an important role in the production of bile hepatocyte growth factor.

Adult↗
PubMed1999

Production of interleukin-10 by alveolar macrophages from lung cancer patients.

Interleukin (IL)-10 is known to be an autoregulatory factor of functions of monocyte macrophages. The purpose of this study was to determine whether IL-10 production by alveolar macrophages (AMs) is altered in patients with lung cancer. AMs were obtained by bronchoalveolar lavage from 25 patients with lung cancer and 14 control patients. The production of IL-10 by AMs was quantitated by enzyme immunoassay with or without stimulation with lipopolysaccharide (LPS). No significant difference in spontaneous and LPS-stimulated IL-10 production by AMs was observed between lung cancer patients and control patients (mean +/- SEM; 288.0 +/- 56.7 vs. 249.6 +/- 58.4 pg ml-1). IL-10 production of LPS-stimulated AMs was not impaired even in lung cancer patients with systemic metastasis. IL-4 failed to suppress LPS-induced production of IL-10 by AMs both in control patients and in lung cancer patients. In eight patients with lung cancer, IL-10 production by AMs was estimated before and after systemic chemotherapy and IL-10 production by LPS-stimulated AMs tended to increase after systemic chemotherapy from 152.3 +/- 51.9 to 278.0 +/- 112.8 pg ml-1. As IL-10 is a potent inhibitor of tumour angiogenesis, an important process of tumour progression, these results suggest that, even in advanced cancer patients, macrophages can produce potent angiogenesis inhibitor and systemic chemotherapy may augment this inhibitory activity in the lung.

Adult↗
PubMed1999

Interleukin 6 in bile as an indicator of liver function after hepatectomy in patients with biliary tract carcinoma.

BACKGROUND: Interleukin (IL) 6 is one of the important components of the early signalling pathways leading to liver regeneration, and has been detected in the bile after liver transplantation. IL-6 concentrations in the bile were studied in an attempt to predict liver function after major hepatectomy for biliary tract carcinoma. METHODS: This study involved 24 patients without cirrhosis who underwent major hepatectomy for biliary tract carcinoma. The bile was sampled regularly through external biliary drainage tubes. IL-6 concentrations in bile and serum were measured using an enzyme-linked immunosorbent assay. RESULTS: Bile IL-6 concentrations increased 37-fold (from mean(s.e.) 56(13) pg/ml before hepatectomy to 2071(398) pg/ml on day 1 after operation) in patients without liver failure after hepatectomy (n = 18) and increased sevenfold (from 71(24) to 530(76) pg/ml) in patients with liver failure after hepatectomy (n = 6). The values were significantly lower in patients with liver failure than in those without liver failure (P < 0.05). The bile IL-6 concentration on day 1 after operation exhibited a significant negative correlation with the maximum serum total bilirubin concentration after hepatectomy. Although serum IL-6 concentrations were also increased in both groups after hepatectomy, there was no significant correlation with postoperative liver function. CONCLUSION: Increased bile IL-6 concentrations after hepatectomy may reflect liver regenerative capacity. Measurement of bile IL-6 concentrations may be clinically useful for the early identification of liver failure after hepatectomy.

Adult↗
PubMed1999

Up-regulation of glomerular extracellular matrix and transforming growth factor-beta expression in RF/J mice.

BACKGROUND: RF/J mice were first reported as a murine model of spontaneous glomerulosclerosis by Gude and Lupton in 1960, but the precise histologic characteristics and immunopathological background of this mouse have not been investigated further. METHODS: Measurements of serum levels of immunoglobulins, anti-single strand DNA (anti-ss-DNA) antibody, complement (C3), and circulating immune complex (IC) were performed. Analyses of glomerular histological and immunopathological lesions in association with the detection of mRNA expression of collagen IV, TGF-beta, matrix protein turnover related enzymes, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) and platelet-derived growth factor (PDGF) were also performed in young (10-week-old) and elderly (60-week-old) RF/J mice with age-matched BALB/C mice as the controls. RESULTS: High levels of serum IgA and IgG from as early as 20 weeks of age were noted in the RF/J mice. Serum anti-ss-DNA antibody of aged RF/J mice increased up to 23% of that of aged MRL-lpr/lpr mice, and serum C3 concentration significantly decreased with age, reaching lower levels than that of BALB/c mice. IgA-IC levels were significantly high compared to BALB/C mice both in the early and late stages of life, whereas IgG-IC levels were high only in mice younger than 20 weeks. Semiquantitative and quantitative analyzes of renal histopathological findings revealed significantly marked and age-related mesangial matrix expansion in RF/J mice, with increasing frequency of global glomerular sclerosis and tubulointerstitial damage. On the other hand, although precise measurements of glomerular cell numbers also showed an apparent augmentation in both young and old RF/J mice compared to BALB/C mice, glomerular cellularity decreased with age in RF/J mice. Immunohistochemical study revealed massive immunoglobulin deposition from a young age in association with significantly higher accumulation of matrix proteins, such as types I and IV collagen and laminin from the early stage of life. In addition, in these glomeruli, transforming growth factor-beta1 (TGF-beta1) was highly expressed both in young and old mice. The mRNA expression of MMP-2 was up-regulated only in the early stage of life. Although PDGF mRNA of RF/J mice was significantly up-regulated in the early stage of life, the differences between the mice disappeared in the late stage of life. CONCLUSIONS: These findings suggest that in RF/J mice, an immunopathological background inducing high serum immunoglobulin and IC levels from the early stage of life is closely related to mesangioproliferative glomerular lesions mediated by PDGF, and that development of massive extracellular matrix accumulation in glomeruli was induced by up-regulated expression of TGF-beta with inappropriate regulation of protein turnover-related enzyme production.

Age Factors↗
PubMed1999

Expression of inducible nitric oxide synthase in human thyroid papillary carcinomas.

To evaluate the relationship between nitric oxide (NO) and carcinogenesis, we assayed 4 human thyroid papillary carcinomas (TPC) and 3 normal thyroid glands for the presence of inducible nitric oxide synthase (iNOS). Using an antibody against iNOS, we observed immunohistochemical staining if iNOS in the TPC samples, but not in normal thyroid. When we incubated TPC samples with antibodies against both iNOS and human leukocyte antigen (LCA), a macrophage marker, we found that while most TPC cells were stained with anti-iNOS antibody, only a few were stained with both. Reverse transcription polymerase chain reaction (RT-PCR) showed that iNOS mRNA was expressed in the samples of TPC, but not in normal thyroid. The sequence of iNOS message in the TPC samples was identical to that previously detected in a human colon cancer cell line. These results suggest that iNOS in human TPC is mostly derived from tumor cells, rather than macrophages, and that it may play a direct role in carcinogenesis.

Base Sequence↗
PubMed1999

Establishment of nurse-like stromal cells from bone marrow of patients with rheumatoid arthritis: indication of characteristic bone marrow microenvironment in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the microenvironment of bone marrow (BM) of patients with rheumatoid arthritis (RA). METHODS: Nurse cell-like BM stromal cell lines were established from BM mononuclear cells of patients with RA. We examined the various characteristics of these cell lines, including morphology, pseudoemperipolesis activity, cell surface markers, cytokine production and hyaluronan (HA) production. RESULTS: These RA BM nurse cell-like lines (RA-BMNC) were of mesenchymal origin and positive for CD44, CD54 and HLA-DR. They were defined as nurse cells because of pseudoemperipolesis activity that allowed lymphocytes to migrate underneath. RA-BMNC lines produced HA and multiple cytokines including interleukin (IL)-6, IL-7, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF). HA production by BM stromal cells was correlated with pseudoemperipolesis activity. RA-BMNC produced significantly higher levels of IL-6, IL-8 and GM-CSF by co-culture with lymphocytes. The cells also produced IL-1beta, G-CSF and tumour necrosis factor only when co-cultured with lymphocytes. The RA-BMNC maintained the growth of CD14+ myeloid cells unique to severe RA. CONCLUSION: The present results both indicate that RA-BMNC are nurse cells and suggest that they may play an important role in the pathogenesis of RA.

Antigens, CD↗
PubMed1999

Comparative study of vocal function after near-total laryngectomy.

OBJECTIVES: To assess vocal function after near-total laryngectomy (NTL) and to compare that with after vertical hemilaryngectomy (VHL), both of which use the laryngeal mucosa as the vibratory tissue. STUDY DESIGN: We retrospectively evaluated 29 patients, 11 of whom underwent NTL and 18 of whom underwent VHL. However, 2 patients failed to speak and 1 patient's voice sample was lost following NTL, so we analyzed the voices of 8 patients who underwent NTL and 18 patients who underwent VHL. METHODS: Vocal function was examined by acoustic and aerodynamic analysis. Acoustic analysis involved the evaluation of pitch, intensity, pitch perturbation quotient, amplitude perturbation quotient, and normalized noise energy. In aerodynamic analysis, we studied the mean airflow rate, vocal efficiency index (alternating current/direct current [AC/DC]), and maximum phonation time. RESULTS: Vocal function except pitch after either NTL or VHL had much variability, but the results following each procedure did not differ significantly. CONCLUSIONS: There are no significant differences between vocal function following NTL and VHL. Fiberscopic examination of the mucosa of the arytenoid was observed to vibrate in patients who underwent NTL, so that the phonatory mechanism after NTL resembled that after VHL.

Adult↗
PubMed1999

Infrequent presence of anti-c-Myc antibodies and absence of c-Myc oncoprotein in sera from lung cancer patients.

To clarify the host immune response and explore a new serological marker of lung cancer, we examined serum c-Myc antigens and auto-antibodies against c-Myc in 68 lung cancer patients and 30 healthy volunteers using bacterially synthesized glutathione S-transferase c-Myc fusion proteins and immunoblotting. The detection rate of anti-c-Myc antibodies was 13.2% (9/68) in lung cancer patients and 3.3% (1/30) in healthy volunteers. These anti-c-Myc antibodies were directed toward exon 2 alone (4/68), exon 3 alone (1/68), and both exon 2 and exon 3 (4/68) of c-Myc. Circulating c-Myc antigen was not detected in any individuals with lung cancer and normal controls. Age, sex, performance status, histology, stage, smoking history, and prior treatment of the patients with and without anti-c-Myc antibodies were not significantly different. The low incidence of anti-c-Myc antibodies and c-Myc antigens in peripheral blood suggests that these examinations are not useful in the serological diagnosis of lung cancer.

Adult↗
PubMed1999

Rapid decalcification using microwaves for in situ hybridization in skeletal tissues.

In situ hybridization histochemistry is the sole tool available for detecting the localization and expression of specific RNA on histological sections under various in vivo conditions. For this paper, we examined the effect of microwave exposure on the time needed for decalcification of skeletal tissues and on the preservation of sensitivity for hybridization signals. Our data show that the use of microwave decalcification reduces the decalcification period while preserving intense hybridization signals for mouse alpha1 chain of procollagen type I mRNA in osteogenic cells in bone. The use of microwave treatment to decalcify skeletal tissues may prevent delay in obtaining experimental results or the loss of signals during in situ hybridization.

Animals↗
PubMed1998

Soluble Fas ligand in the joints of patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To investigate the expression and function of Fas ligand (FasL),which can be in a membrane-bound or soluble form, in the joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The concentration of soluble FasL (sFasL) in serum and synovial fluid (SF) from 24 OA and 38 RA patients was measured using an enzyme-linked immunosorbent assay. The expression of FasL on SF lymphocytes (SFL) and peripheral blood lymphocytes (PBL) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. A cytotoxic killing assay of membrane-bound FasL and purified sFasL against cultured synovial cells was also performed. RESULTS: Soluble FasL was detected in the SF of patients with RA and OA, but not in their serum. The concentration of SF sFasL was remarkably higher in patients with severe RA than in patients with mild RA or with OA. RT-PCR showed that SFL, but not PBL, from RA patients expressed messenger RNA for FasL. Membrane-bound FasL induced apoptosis in cultured synovial cells from the RA and OA patients, but naturally processed human sFasL did not. CONCLUSION: SFL from RA patients expressed FasL, and cleaved sFasL accumulated in the SF of inflamed joints. The different killing activity of membrane-bound FasL and sFasL against synovial cells may regulate Fas-mediated apoptosis in synovial cells.

Aged↗
PubMed1998

Lobectomy: video-assisted thoracic surgery versus posterolateral thoracotomy.

BACKGROUND: Video-assisted lobectomy has been adopted by many thoracic surgeons, because it is a less invasive approach to small peripheral lung cancers. However, some authors disagree that video-assisted lobectomy is less invasive than traditional thoracotomy and lobectomy. The purpose of this study was to evaluate the advantages of video-assisted lobectomy over posterolateral thoracotomy and lobectomy in terms of pain-related morbidity. METHODS: A total of 70 patients with clinical T1N0M0 non-small-cell lung carcinomas underwent lobectomy with complete mediastinal lymphadenectomy. Of these 35 underwent posterolateral thoracotomy (between April 1994 and December 1995; open group), and 35 underwent video-assisted thoracic surgery (VATS) (between January and December 1996; VATS group). RESULTS: Although the operative time was significantly longer in the VATS group (p = 0.04), the intraoperative blood loss was significantly less (p = 0.03). No significant differences were found for the two groups with respect to the total number of mediastinal lymph nodes dissected or duration of chest tube drainage. Postoperative pain was less severe as determined by the number of doses of analgesics required between postoperative days 0 and 7 (p < 0.0001), and the length of postoperative hospitalization was shorter in the VATS group (p < 0.0001). CONCLUSION: Video-assisted lobectomy is associated with decreased postoperative pain and shortened length of postoperative hospitalization, when compared with posterolateral thoracotomy and lobectomy.

Adult↗
PubMed1998

Evaluation of 18-hour lung preservation with oxygenated blood for optimal oxygen delivery.

BACKGROUND: Previous studies have shown that availability of oxygen during lung preservation to maintain aerobic metabolism may be essential for the optimal viability of preserved lung tissue. The purpose of this study was to evaluate lung preservation with oxygenated blood for optimal oxygen delivery to the lung graft in a rabbit model. METHODS: Eighteen excised rabbit lungs were flushed and stored for 18 hours at 10 degrees C with one of the following: Euro-Collins solution (EC; n=6), oxygenated homologous blood (OB; n=6), or low-potassium dextran solution (LPD; n=6). Poststorage lung functions were evaluated with isolated, blood-perfused lung model for 10 minutes. RESULTS: The mean oxygen tensions after reperfusion for the EC, OB, and LPD groups (47.0+/-2.8, 76.9+/-13.1, 96.2+/-10.9 mm Hg at 10 minutes, respectively) were significantly different throughout the perfusion period (EC < OB < LPD, p < 0.05; EC < LPD, p < 0.01). Pulmonary artery pressure during the reperfusion period in the EC group (35.8+/-4.4 mm Hg at 10 minutes) was higher than that in the OB and LPD groups (29.8+/-4.3 and 22.4+/-2.2 mm Hg, respectively) (EC > OB, EC > LPD, p < 0.05). However, the E-selectin level in the reperfused blood in the OB group (5.04+/-0.24 ng/mL) was significantly elevated compared with that in other groups (EC, 3.56+/-0.54; LPD, 2.92+/-0.35 ng/mL, p < 0.05), which indicated enhanced neutrophil recruitment in the OB group. Comparisons of thrombomodulin and endothelin among the three groups did not reach statistical significance. CONCLUSIONS: We conclude that OB may enhance lung preservation as compared with EC solution, probably through its enriched oxygen delivery during storage and extracellular composition. However, the availability of oxygenated blood does not exceed that of LPD solution because of augmented neutrophil recruitment, which may activate neutrophil-endothelial interactions.

Animals↗
PubMed1998

Comparative analysis of interleukin 15 and interleukin 2 for induction of killer activity and of type 2 cytokine production by mononuclear cells from lung cancer patients.

Interleukin (IL) 15 is a novel cytokine with IL-2-like activity. In this study, we examined the effect of IL-15 on induction of non major histocompatibility complex (MHC)-restricted killer activity and of type 2 cytokine production by peripheral blood and pleural mononuclear cells (MNCs), from 34 lung cancer patients and 20 control subjects. IL-15 induced significant killer activity in blood MNCs from lung cancer patients as well as control subjects against a small-cell lung cancer cell line (SBC-3). Effective killer induction by IL-15 was observed even in blood MNCs and pleural MNCs from the site of tumour growth in advanced lung cancer patients. IL-12 had an additive effect with a suboptimal dose of IL-15 in induction of killer activity. In the case of MNCs from lung cancer patients, IL-10 production was more prominent when cells were incubated with IL-2 than with IL-15. IL-5 production was observed in MNCs from lung cancer patients stimulated with IL-2, but not with IL-15. These observations suggest that IL-15, by virtue of its lesser induction of type 2 cytokine, may be a better candidate than IL-2 for lung cancer immunotherapy.

Adult↗
PubMed1998

Mesangiolytic glomerulopathy in severe congestive heart failure.

To study the glomerular morphological abnormalities in congestive heart failure (CHF), we analyzed 27 autopsy cases without other causes of renal disease. Their mean age was 59 years, and they showed mild prerenal azotemia. They had generally been treated with digitalis and diuretics, and a few of them with captopril or nifedipine. The abnormal glomerular findings of enlargement, hyperemia, and mesangial thickening were observed at high frequencies (61%, 64%, and 57%, respectively). They characteristically showed mesangiolysis (ML) by the findings of microaneurysms (81%) and mesangial degeneration (70%) such as loose reticular matrix and poor matrix area. In addition, glomerular infiltration of mononuclear leukocytes including macrophages was noted in 70% of the cases. Glomerular enlargement was not correlated with the grade of hyperemia, but it was correlated with the grade of ML index of % glomeruli with microaneurysms (F = 7.22, p < 0.004). There was an inverse relationship between the grades of mesangial thickening and of the ML index (P < 0.005). The number of glomerular leukocytes was positively correlated with mean glomerular size (P < 0.002) and with the ML index (P < 0.03). Notably, the glomerular macrophage-positive cases showed a prominently higher mean ML index than the negative cases (P < 0.005). There was an inverse correlation between the mean glomerular size and the partial oxygen pressure in arterial blood (PaO2; P < 0.01), and a positive correlation between the mean glomerular size and hematocrit (Hct) levels (P < 0.02). The cases positive for mesangiolytic mesangial degeneration showed significantly lower PaO2 values than the cases negative for this lesion (P < 0.04). In the analysis of the various causes of CHF, the patients with congenital cardiac anomalies showed mean levels of the lowest PaO2 (P < 0.02) and the highest Hct (P < 0.03) and histologically the largest mean glomerular size (P < 0.04). There was no difference in the ML index and the glomerular leukocyte number among the subgroups classified by the causes. These results indicate that ML associated with glomerular enlargement is the major glomerular abnormality characteristic in patients with severe CHF and suggest that glomerular infiltration of leukocytes, especially of macrophages, should play an important role in the progression of both ML and glomerulomegaly. The contributions of persistent hypoxia and up-regulated angiotensin II as the causative factors of these glomerular abnormalities in congestive heart failure are discussed.

Adult↗
PubMed1998

An autopsy case of cytokeratin 7-positive minute adenocarcinoma of the lung with systemic metastases.

We describe a 60-year-old woman with leg pain. Although metastatic bone tumor and atypical cells mimicking signet-ring cells in the bone marrow picture were observed, systemic survey revealed no primary lesion. The patient died two months after admission from systemic progress of the disease. Autopsy revealed a small focus of adenocarcinoma within the right upper lobe of the lung and systemic metastases without any particular changes in the gastrointestinal tract. The tumor cells of the lung were diffusely positive for cytokeratin 7, whereas cytokeratin 20 immunoreactivity was weak and focal, and that supported the lung origin of the present tumor. Moreover, the tumor cells in the bone marrow showed a similar pattern in immunoreactivity. These findings suggest that cytokeratin 7 and cytokeratin 20 immunoreactivity is helpful for the premortem diagnosis of the metastatic tumor of unknown origin.

Biomarkers, Tumor↗