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Biomedical subjects

Mine Harada

Publications and source records attributed to Mine Harada.

At least 181 records · Page 10Linked to original sources
PubMed2002

Respiratory variation in superior vena cava flow in patients with chronic obstructive pulmonary disease: estimation of pulmonary hypertension using Doppler flow index.

Patients with chronic obstructive pulmonary disease (COPD) are difficult to assess by conventional transthoracic echocardiography (TTE) because of emphysematous lungs or mediastinal deviation. We hypothesized that superior vena cava (SVC) flow is related to pulmonary circulation and may be useful for the detection of pulmonary hypertension (PH) in patients with COPD that cannot been assessed by direct evaluation using the tricuspid regurgitant Doppler velocity. SVC Doppler flow velocities were examined in 46 patients with COPD and the pressure gradient between the right ventricular and right atrial pressure (RV-RADeltaP) was calculated by tricuspid regurgitant Doppler velocities. The patients were divided into 2 groups: 11 patients with PH (RV-RADeltaP > 25 mm Hg) were compared with 35 without PH. There was no significant difference in the maximal SVC peak systolic forward flow velocity during inspiration (INS) between these 2 groups. However, the minimal SVC peak systolic forward flow velocity during expiration (EXP) in the group with PH was significantly higher than that in the group without PH (37.4 +/- 20.0 cm/s vs 26.4 +/- 8.5 cm/s, P =.01). Linear regression analysis revealed a significant correlation between RV-RADeltaP and the EXP/INS ratio (r = 0.61, P <.001). In COPD patients with PH, the increased expiratory SVC systolic flow supplemented the preload for the impaired right ventricular filling flow caused by PH, thereby maintaining the transtricuspid driving pressure. Our observation suggests that respiratory variation in SVC systolic forward flow may be a sensitive Doppler flow index for evaluating severity of PH in patients with COPD that cannot been assessed by conventional TTE.

Aged↗
PubMed2002

Molecular mechanisms of lipopolysaccharide-induced cyclooxygenase-2 expression in human neutrophils: involvement of the mitogen-activated protein kinase pathway and regulation by anti-inflammatory cytokines.

Neutrophils are an important cellular source of proinflammatory mediators, whose regulation may be of potential benefit for the treatment of a number of inflammatory diseases. However, the mechanisms of lipopolysaccharide (LPS)-induced neutrophil activation and its regulation by anti-inflammatory cytokines have not yet been fully elucidated. Recent studies have revealed that mitogen-activated protein kinases (MAPK) play a crucial role in the generation of proinflammatory mediators in some cell types. Therefore, we conducted this study to determine whether MAPK activation could be involved in prostaglandin E(2) (PGE(2)) production and cyclooxygenase (COX)-2 expression in LPS-stimulated human neutrophils. PD98059 (MEK1 inhibitor) and SB203580 (p38(MAPK) inhibitor) reduced PGE(2) production as well as COX-2 expression in LPS-stimulated neutrophils. In addition, both extracellular signal-regulated protein kinase (ERK) and p38(MAPK) were phosphorylated and activated in time- and dose-dependent manners. Since we previously showed that IL-10 and IL-4 similarly inhibited COX-2 expression in LPS-stimulated neutrophils, we next tested the effects of IL-10 and IL-4 on the phosphorylation and activation of both kinases. IL-10 inhibited the phosphorylation and activation of p38(MAPK), but not ERK. In addition, IL-4 caused a marginal inhibition in the activation of p38(MAPK). Taken together, these results suggest that both ERK and p38(MAPK) pathways are involved in LPS-induced COX-2 expression and PGE(2) production in neutrophils, and IL-10 and IL-4 inhibit neutrophil prostanoid synthesis by down-regulating the activation of p38(MAPK).

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Spontaneous regression of metastatic endometrial stromal sarcoma.

Spontaneous regression of malignancy is rare and there appear to be no reports of spontaneous regression of endometrial stromal sarcoma. We report a rare case of metastatic endometrial stromal sarcoma that regressed spontaneously. A 58-year-old woman was admitted to hospital in January 1996 when her chest radiograph showed multiple nodular shadows in the left lower lung field. Computed tomography of the chest revealed bilateral nodules. Segmentectomy of the left lower lobe was performed by thoracoscopy. She had a past history of uterine myoma with metrorrhagia for which she had undergone a hystero-oophorectomy 10 years earlier. She also had a vaginal polyp removed 1 year earlier. The lung pathology was studied and the surgical specimens of the uterus and vagina were re-examined. The diagnosis was endometrial stromal sarcoma primarily arising in the uterus. The vaginal polyp and the pulmonary nodules were considered to be metastases. Samples of lung and vaginal tissues were positive for both estrogen and progesterone receptors. The patient was discharged without treatment in February 1996 and followed up in the outpatient clinic. The tumor shadow measuring 2 mm in diameter on admission was enlarged to 4 mm in diameter 1 year later. Surprisingly, spontaneous regression of the lung disease occurred at 33 months, the tumor size decreasing to 2 mm in diameter and to 1 mm at 46 months. No evidence of tumor enlargement was detected at the last follow-up in July 2001. Although the precise mechanism of tumor regression is unknown, metastatic endometrial stromal sarcoma may spontaneously regress.

Endometrial Neoplasms↗
PubMed2002

Matrix metalloproteinase-2 in pancreatic juice for diagnosis of pancreatic cancer.

INTRODUCTION: Matrix metalloproteinase-2 (MMP-2) has an activity to degrade type IV collagen and is associated with invasion angiogenesis of malignant tumor. AIM: A diagnostic value of MMP-2 in pancreatic juice was studied in the diagnosis of pancreatic cancer. METHODOLOGY: Using gelatin zymography, active MMP-2 and proMMP-2 were determined in pancreatic juice obtained endoscopically from 12 patients with pancreatic cancer, 11 with chronic pancreatitis, and 7 control subjects. RESULTS: ProMMP-2 was detected in 12 of 12 patients (100%) with pancreatic cancer, 6 of 11 (54.5%) with chronic pancreatitis, and 3 of 7 (42.9%) controls. Active MMP-2 was detected in 11 patients (91.6%) with pancreatic cancer, 2 (18.2%) with chronic pancreatitis, and none of the control subjects. An activation ratio of MMP-2 (active MMP-2/total MMP-2) in pancreatic juice is significantly higher in pancreatic cancer (23.4 +/- 4.4%, mean +/- SE) than in chronic pancreatitis (2.1 +/- 1.7%) and controls (0%) (p < 0.01). Active MMP-2 was also detected in pancreatic juice from three cases of small pancreatic cancer (tumor <2 cm in diameter). CONCLUSION: Our observation suggests that detection of active MMP-2 in pancreatic juice using gelatin zymography may be useful for the diagnosis of pancreatic cancer.

Adult↗
PubMed2002

Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.

Although the arrhythmogenic effects of interferon (IF) have been reported in clinical practice, the experimental data are limited. Therefore, these effects were investigated in in vivo and Langendorff-perfusion studies using 3 different groups of rats (ie, control, aorta-banded, and deoxycorticosterone acetate (DOCA)-salt hypertension groups) in the presence or absence of isoproterenol. In the perfusion study, human recombinant IF-alpha (< or =15,000 U/ml) alone induced irreversible atrioventricular blockade in all groups, whereas this agent (< or =1,500 U/ml) caused negative inotropism and ventricular tachyarrhythmias (arrhythmic score greater in the order of DOCA-salt>aorta-banded = control group) in the preparations pretreated with isoproterenol (10(-9) mol/L). In an in vivo study, IF-alpha (6x10(6) U/kg) resulted in ventricular tachyarrhythmias only in the presence of isoproterenol (10 mg/kg), as in the perfusion study (arrhythmic score; DOCA-salt>aorta-banded>control). In conclusion, the arrhythmogenesis of IF-alpha is potentiated in pathophysiological conditions such as cardiac hypertrophy or elevated sympathetic activity.

Animals↗
PubMed2002

Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation.

Cardiac complications are major limiting factors regarding the success of high-dose chemotherapy supported by blood stem cell transplantation (BSCT). The cardiotoxicity of cyclophosphamide remains obscure relative to that of anthracyclines. The aim of this study was to estimate noninvasively the cardiotoxicity of cyclophosphamide administered during the pretransplant conditioning of BSCT for patients with various hematological diseases. A total of 27 consecutive patients were divided into two groups depending on the conditioning regimen, ie, group A (n=15) which received cyclophosphamide (median dose of 120 mg/kg; range 100 to 200 mg/kg) and group B (n=12) which did not. Ultrasound cardiograms (UCG) and signal-averaged electrocardiograms (SAECG) were recorded in the two groups both preceding and following the BSCT. There were no statistical intergroup or intragroup differences in left ventricular (LV) dimensions or contractile function. Significant (P<0.01) posttransplant increases in interventricular septal wall thickness and Ap/Ep ratio were noted in group A. Moreover, the filtered QRS duration as estimated by SAECG was prolonged (P<0.05) whereas the summated LV voltage (S(V1)+R(V5)) was reduced in the posttransplant period only in group A. These results suggest that early cyclophosphamide cardiotoxicity was characterized by LV diastolic rather than systolic dysfunction. These findings may contribute to acute hemodynamic deterioration observed after cyclophosphamide-containing conditioning chemotherapy.

Adolescent↗
PubMed2002

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer.

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.

Adenocarcinoma↗
PubMed2002

Comparison of chemosensitivity tests: clonogenic assay versus MTT assay.

When the development of chemotherapeutic agents reaches the clinical trial stage, it is necessary to perform drug sensitivity tests quickly in order to select the most promising agents for the treatment of cancer. In order to assess the possibility of using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a substitute for the human tumor clonogenic assay (HTCA), we evaluated the correlation between the results obtained by these 2 assays in 5 human lung cancer cell lines. The correlation coefficient between the results of the HTCA and the MTT assay was 0.673, indicating a relatively good correlation. The correlation was most prominent in platinum analogues (r = 0.939) and good in anthracyclines/anthracenedione (r = 0.611). However, no significant correlation was observed in vinca alkaloids, etoposide, irinotecan, SN-38 (an active metabolite of irinotecan), and rhizoxin. The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione. These results suggest that the MTT assay may be more convenient and quickly performed than the HTCA and can replace HTCA in evaluating the effects of anticancer agents, especially the platinum analogues and anthracyclines/anthracenedione.

Antineoplastic Agents↗
PubMed2002

Synergistic effects of topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin, and irradiation in a cisplatin-resistant human small cell lung cancer cell line.

7-ethyl-10-[4-(1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, a topoisomerase I (topo I) inhibitor, is one of the most active agent against lung cancer, and its radiosensitizing effect has been reported recently. We evaluated a combination in vitro effect of irradiation and 7-ethyl-10-hydroxy-CPT (SN-38), an active metabolite of 7-ethyl-10-[4- (1-piperidyl)-1-piperidyl] carbonyloxy-camptothecin, on a human small cell lung cancer cell line (SBC-3) and its cisplatin-resistant subline (SBC-3/CDDP). Growth-inhibitory effects of irradiation with or without SN-38 were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A modified isobologram method was used to evaluate the treatment interaction. The combination of irradiation and SN-38 showed a synergistic inhibitory effect on the growth of SBC-3/CDDP despite its cross-resistance to irradiation and SN-38. In contrast, the same combination showed only an additive effect on the growth of parental SBC-3 cells. There was no significant difference in topo I protein expression between these two cell lines. In SBC-3 cells, topo I catalytic activity was suppressed by 4 Gy of irradiation, without a decrease of nuclear topo I protein, whereas the exposure of SBC-3 cells to 1 microM SN-38 subsequent to irradiation showed no remarkable additional effects on both topo I activity and protein content. On the other hand, in SBC-3/CDDP cells, topo I activity was unchanged by irradiation, but the subsequent exposure to SN-38 gave rise to a decrease in topo I activity, which was accompanied by a significant decrease in the topo I protein content (P = 0.02). These observations may indicate that SN-38 induces sequestration of topo I onto DNA in radiation-treated SBC-3/CDDP cells and suggest that the synergistic effect of irradiation and SN-38 in SBC-3/CDDP cells was considered attributable to DNA repair-related enhanced recruitment of topo I onto the damaged DNA.

Antineoplastic Agents↗
PubMed2002

Lung cancer prevention with (-)-epigallocatechin gallate using monitoring by heterogeneous nuclear ribonucleoprotein B1.

Considering the problems involved in prevention of human lung cancer, growth inhibition of human lung cancer cell line A549 was studied with emphasis on two parameters: green tea polyphenols, such as (-)-epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG); and heterogeneous nuclear ribonucleoprotein B1 (hnRNP B1), a new biomarker of human lung cancer which is highly expressed in the very early stages of human lung cancer. The inhibitory potencies of green tea polyphenols were compared with those of genistein as a control. EGCG or ECG and genistein as a control dose-dependently inhibited the growth of A549 cells, which strongly elevated hnRNP B1 protein, and increased G2/M phase cells associated with induction of apoptotic cells. The results were confirmed by previous evidence with human lung cancer cell line PC-9. Some larger differences in mechanisms of action between green tea polyphenols and genistein were presented. Treatment of A549 cells with EGCG, ECG or genistein significantly inhibited the expression levels of hnRNP B1 mRNA and the elevated levels of hnRNP B1 protein, both of which are constitutively elevated in cancer cells. Furthermore, both EGCG and genistein inhibited the promoter activity of hnRNP A2/B1 gene expression, with IC50 values 29 microM for EGCG and 66 microM for genistein, suggesting the interaction of EGCG or genistein with the transcriptional complex. Looking at our results here, and those of previously reported epidemiological studies with green tea, we discuss the steadily accumulating evidence that clinical trials with green tea extract would be an efficient means of lung cancer prevention.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Differentiation of monoblastic cell line UG3 into leukemic dendritic cells.

Dendritic cells (DCs) are known to be generated from leukemic clone from patients with acute and chronic leukemia when cultured in the presence of combination of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4. However, there have been few reports that showed DCs could be effectively differentiated from human leukemia cell lines. In this study, we have shown that a human monoblastic cell line, UG3, was inducible to differentiate into DCs in the presence of GM-CSF and TNF-alpha along monocyte-macrophage lineage. These DCs, consistently displayed dendritic morphology, phenotypes and allogeneic T-cell stimulating capacity. UG3 cells thus may represent a suitable model to further elucidate characteristics of DC differentiation.

Antigen Presentation↗
PubMed2002

Antilung cancer effect of WT1-specific cytotoxic T lymphocytes.

We and other groups have recently reported that CTLs that specifically recognize a peptide derived from WT1 lyse leukemia cells in a HLA class I-restricted manner. Because WT1 is expressed in various solid tumors as well as in leukemic cells, we investigated whether WT1-specific CTLs can also inhibit the growth of lung cancer by examining their cytotoxic activity against lung cancer cell lines in vitro and their inhibitory effect on the growth of human lung cancer cells engrafted into nude mice. The WT1 transcript was detected in most of the lung cancer cell lines examined. A WT1-specific, HLA-A24-restricted CTL clone (designated TAK-1) exhibited cytotoxicity against lung cancer cell lines bearing HLA-A24 but did not lyse cells lacking this HLA. This suggests that the target antigen for TAK-1 on HLA-A24-positive lung cancer cells is the naturally processed WT1 peptide. Adoptive transfer of TAK-1 into nude mice that had been engrafted with a HLA-A24-positive lung cancer cell line resulted in inhibition of cancer cell growth and prolonged survival. These findings strongly suggest that WT1 is a universal tumor-associated antigen and that WT1-targeting immunotherapy offers a potentially effective treatment option for lung cancer as well as leukemia.

Animals↗
PubMed2002

Sick sinus syndrome disclosed by the successful radiofrequency catheter ablation of persistent common atrial flutter.

Sick sinus syndrome was disclosed in a 77 year-old man after a radiofrequency (RF) linear catheter ablation of cavotricuspid isthmus for persistent common atrial flutter. Prolongation of corrected sinus node recovery time, sinoatrial conduction time and AH interval, as observed after RF ablation, suggested binodal (sinus as well as atrioventricular node) dysfunction. Adams-Stokes syndrome due to sinus arrest was encountered on the day of RF ablation and a permanent DDD pacemaker was implanted consequently. Our experience indicates that careful observation is very important after the RF ablation when atrial flutter is associated with sick sinus syndrome. The present case suggests that binodal dysfunction underlies persistent atrial flutter and vice versa.

Aged↗
PubMedDate not supplied

Cholesterol embolization treated with corticosteroids--two case reports.

Cholesterol embolization (CE) is a potentially serious complication associated with invasive arterial maneuvers, in which standard therapy has not been established. We experienced two cases of CE in patients with severe atherosclerosis whose renal function deteriorated within a few months after invasive arterial maneuvers. CE was confirmed either by renal biopsy (case 1) or skin biopsy (case 2). Oral administration of prednisolone at a daily dose of 30 mg (0.4 mg/kg) was effective to improve their renal function. Our observation suggests that corticosteroid therapy may be beneficial in some patients with CE.

Aged↗