Biomedical subjects

H Deguchi

Publications and source records attributed to H Deguchi.

At least 55 records · Page 3Linked to original sources

PubMed1998

Prothrombin and its derivatives stimulate motility of melanoma cells.

Several studies indicated that activation of the clotting system may promote the growth and the invasive behavior of tumor cells. In the present study, we evaluated the migratory response of various melanoma cell lines to several clotting factors and prothrombin derivatives (thrombin, fragment 1, fragment 2 and kringle 1 fragment). Prothrombin, thrombin and fragment 1 stimulated chemotaxis of the murine (K-1735 M2, X21) and human A375 (SM) melanoma cell lines. Prothrombin and prothrombin fragment 1 showed their maximal chemotactic activity at 0.5 approximately 1 microM. Chemotaxis induced by thrombin was inhibited by hirudin, but not that induced by prothrombin or fragment 1. Other clotting proteins and the fragment 2 and kringle 1 fragment of prothrombin did not elicit chemotactic activity. Checkerboard analysis indicated that motility was directional with a significant chemokinetic component. The K-1735 M2 cells also migrated in a concentration-dependent manner to substratum-bound insoluble prothrombin, thrombin or fragment 1. Ligand binding assays showed that both prothrombin and fragment 1 bound to K-1735 M2 cells with apparent Kds of 0.5 microM. This binding was inhibited by an excess concentration of unlabeled prothrombin and fragment 1 but not by similar concentrations of other prothrombin fragments. These findings suggest that prothrombin and its fragment 1 exert chemotactic activity on melanoma cells by different mechanisms and different binding sites from that induced by thrombin.

Animals↗

PubMed1997

Dilazep, an antiplatelet agent, inhibits tissue factor expression in endothelial cells and monocytes.

Dilazep, an antiplatelet agent, is generally used as an antithrombotic drug in clinical practice. Dilazep is also known to exert cytoprotective and antioxidant effects on endothelial cells. However, its effect on the endothelial or monocyte procoagulant activity is unknown. In the current study, the effect of dilazep on the expression of tissue factor (TF) in human umbilical vein endothelial cells (HUVECs) after the stimulation with tumor necrosis factor-alpha (TNF), thrombin, or phorbol 12-myristate 13-acetate (PMA) was evaluated. We also evaluated the effect of dilazep on TNF (1,000 U/mL)-induced TF expression on monocytes. Dilazep inhibited TF activity induced on HUVECs by each stimulant, TNF (1000 U/mL), thrombin (25 nmol/L), or PMA (5 nmol/L) in a dose-dependent fashion (1 to 100 microg/mL). TF activity decreased to approximately 10% after treating with 100 microg/mL of dilazep. Dilazep also blocked the expression of TF antigen induced by each stimulant on the surface of HUVECs as determined by flow cytometric analysis. In addition, in HUVECs, it significantly decreased the expression of TF mRNA and the total TF antigen induced by thrombin or PMA, but not those induced by TNF, suggesting that dilazep blocks the TF expression induced by PMA or thrombin at a transcriptional level and that induced by TNF at a posttranscriptional level. Western blot analysis showed that dilazep reduces the accumulation of native TF but increases that in lower molecular weight TF derivatives. The adenosine receptor antagonist, 8-(p-sulfophenyl) theophylline, partially counteracted the anticoagulant activity of dilazep on HUVECs, thereby suggesting that the inhibitory effect of dilazep on TF expression in HUVECs depends, at least in part, on its adenosine potentiating activity. Dilazep also inhibited TNF-induced TF expression on monocytes in a dose-dependent fashion (0.1 to 100 microg/mL). In brief, the current study showed for the first time that dilazep, a commonly used antiplatelet drug, strongly inhibits the TF expression in HUVECs and monocytes. Dilazep may have a potent therapeutic value in patients with hypercoagulable state for its inhibitory property on the procoagulant activity of endothelial cells and monocytes.

Adenosine↗

PubMed1997

Anti-beta2-glycoprotein I (beta2GPI) monoclonal antibodies with lupus anticoagulant-like activity enhance the beta2GPI binding to phospholipids.

beta2-Glycoprotein I (beta2GPI), a plasma glycoprotein with phospholipid-binding property, is known to be the actual target antigen for autoimmune type anticardiolipin antibodies (aCLs). Certain groups of aCLs (anti-beta2GPI antibodies) exert lupus anticoagulant (LA) activity and perturb the function of vascular endothelial cells. This investigation aimed at highlighting some insights into the molecular basis by which aCLs exert their biological effects by using anti-beta2GPI mAbs with well-characterized epitopes from mice and from patients with antiphospholipid syndrome. Anti-beta2GPI mAbs directed against the third domain (Cof-20 and Cof-22) and fourth domain (Cof-21, EY1C8, and EY2C9) of beta2GPI inhibited the thrombin generation induced by Russell's viper venom in diluted plasma and that induced by the prothrombinase complex reconstituted with purified clotting factors. This anticoagulant activity was abrogated in the presence of an excess amount of phospholipids, thus resembling the LA activity. In stark contrast, anti-beta2GPI mAbs directed against the fifth domain and the carboxy-terminal region of the fourth domain showed no LA-like activity. These findings suggest that the LA activity of anti-beta2GPI antibodies depends on their epitope specificity. Experiments carried out to clarify the mechanism of the LA activity showed that anti-beta2GPI mAbs with LA-like activity, but not those without this effect, enhance the beta2GPI binding to phospholipids. In addition, the F(ab')2 fragment, but not the Fab' fragment, of the anti-beta2GPI mAbs was found to enhance the LA activity and the beta2GPI binding to phospholipids, suggesting that anti-beta2GPI antibodies induce formation of multiple complexes of beta2GPI on the surface of phospholipids because of their bivalent property. This clustering of beta2GPI molecules induced by anti-beta2GPI antibodies, probably because of their multivalent property and epitope specificity, might hinder the lateral mobility and activation of clotting factors on the surface of phospholipids and thus exert LA activity. Clustering of beta2GPI molecules may also explain the molecular mechanism by which anti-beta2GPI antibodies alter the function of leukocytes and endothelial cells. The well-documented heterogeneous LA activity of aCLs (anti-beta2GPI antibodies) may also be explained by their epitope specificity.

Animals↗

PubMed1997

Prothrombin kringle 1 domain interacts with factor Va during the assembly of prothrombinase complex.

The kringle 2 domain of prothrombin has been shown to interact with factor Va during the activation of prothrombin by the prothrombinase complex composed of factor Xa, factor Va, negatively charged phospholipids and Ca2+ ions. However, contradictory results have been reported about the role of the kringle 1 domain of prothrombin during the assembly of the prothrombinase complex. In an attempt to clarify the role of the kringle 1 domain of prothrombin, its effect on the activation of prothrombin by the prothrombinase complex and its direct binding to human factor Va were assessed. Comparative evaluation with the effects caused by other prothrombin structural components [a fragment 1 (gamma-carboxyglutamic acid and kringle 1 domains), a kringle 2 domain and a catalytic protease domain] was also performed. In the presence of factor Va, each kringle 1 and kringle 2 fragment significantly inhibited the factor Xa-catalysed prothrombin activation in the absence of phospholipids. However, in the absence of both factor Va and phospholipids, kringle 2 fragment, but not kringle 1 fragment, inhibited prothrombin activation. Evaluation of the molecular interaction of the kringle domains with factor Va in assays with solid-phase phospholipid vesicles showed that each kringle 1 and kringle 2 fragment inhibited the prothrombinase complex activity. Assessment of the direct binding of prothrombin and each kringle domain of prothrombin with factor Va by fluorescence polarization showed that prothrombin, kringle 1 and kringle 2 fragments bind directly to factor Va with dissociation constants of 1.9+/-0.1, 2.3+/-0.1 and 2.0+/-0.4 microM (means+/-S.D.) respectively. These findings suggest that both kringle 1 and 2 domains of prothrombin interact with factor Va during the assembly of the prothrombinase complex.

Blood Coagulation↗

PubMed1997

Plasma-activated factor VII level in patients positive for lupus anticoagulant.

We examined plasma levels of activated factor VII (F VIla) in 50 patients positive for lupus anticoagulant (LA), in 83 patients negative for LA, and in 10 healthy volunteers as controls. Plasma F VIIa was present in healthy volunteers; its level was significantly increased, compared to the level in the controls, in patients with thrombosis, collagen diseases, and disseminated intravascular coagulation (DIC), suggesting that it reflected a thrombotic state. Plasma F VIIa was correlated with thrombin-antithrombin complex (TAT) in patients negative for LA but showed no such correlation in those positive for LA. Plasma F VIIa was negatively correlated with activated partial thromboplastin time (APTT) in patients positive for LA, but not in those negative for LA, suggesting that LA could inhibit the F VIIa assay system. Plasma F VIIa level was significantly increased in patients with thrombotic diseases; however, in patients positive for LA, it is possible that increased plasma F VIIa level may not be correlated with thrombogenicity.

Collagen Diseases↗

PubMed1997

Evolution to dilated cardiomyopathy from acute eosinophilic pancarditis in Churg-Strauss syndrome.

We describe the clinical manifestations of a patient with Churg-Strauss syndrome who presented with severe acute cardiac involvement and whose disease evolved to dilated cardiomyopathy (DCM), with special reference to the histopathological findings. Endomyocardial biopsies, conducted sequentially, three times within 10 months, revealed severe eosinophilic endomyocarditis in the acute phase, interstitial fibrosis in the subacute phase, and endocardial thickening with mural thrombi, at 10 months. Although acute inflammation associated with elevation of eosinophil granule proteins subsided with steroid therapy, left ventricular dilatation with reduced contractility progressed. A subgroup of DCM is not considered to be idiopathic but, rather, an aftereffect of hypereosinophilic heart disease.

Acute Disease↗

PubMed1997

Sensation of breathlessness and respiratory oxygen cost during cycle exercise with and without conscious entrainment of the breathing rhythm.

The conscious entrainment of respiratory rhythm to exercise rhythm (ENT) has been hypothesized to alleviate breathing discomfort and reduce the oxygen (O2) cost of ventilation with a resulting decrease in total O2 uptake (VO2) during rhythmic exercise. This hypothesis has been tested in the study reported here. Eight female subjects performed cycle exercise at 50 rpm under two work load conditions of 40% and 60% of maximal VO2. During a 30-min exercise period at each work load, each subject was asked to breathe under two conditions for 15 min each: (1) spontaneously (non-ENT run), and (2) deliberately entraining the breathing rhythm to the cycling rhythm at preferred coupling ratios of the two rhythms (ENT run). In the ENT run, most subjects chose a ratio of 1:2. In each run, pulmonary ventilation (VE), total VO2 and the breathlessness sensation (BS) were measured at 4-5 min. BS was assessed according to a Borg category scale. The remaining 10 min of each 15-min run were allotted for measurement of the O2 cost of ventilation (delta VO2/delta VE), assessed by a hypercapnia-induced hyperventilation method in which the VO2 of the respiratory muscles (VO2RM) was calculated by multiplying delta VO2/delta VE by the prevailing VE. On average, there were no significant differences in any of the variables, VO2, delta VO2/delta VE, VO2RM and BS, between the non-ENT and ENT runs performed at any work load. However, there were wide variations among the subjects in the differences (delta) between the two runs, and significant correlations were found between delta VO2 vs delta VE, delta VO2 vs delta VO2RM, and delta BS vs delta VO2RM of individual subjects. These results indicate that reductions of the total VO2 and BS with ENT could occur in subjects in whom the VO2RM decreased during ENT.

Adult↗

PubMed1997

[The study of urgent pulmonary resections for lung cancer accompany with pneumonia].

We studied 10 lung cancer patients with pneumonia insusceptible of conservative treatment. All patients underwent urgent pulmonary resection to control their pneumonia induced by the tumor and to cure the cancer. The causes of pneumonia were bronchial obstruction by the tumor itself or aspiration of the tumor necrosis. The patients comprised 9 men and 1 women. The age range was 37 to 72 years with a median age of 57 years. There were obstructive pneumonia in 3 patients and aspiration pneumonia in 7 cases. The average size of tumor was about 4.7 and 7.5 cm, respectively. The histological type of lung cancer was squamous cell carcinoma in 6 and adenocarcinoma in 4. There were 1 stage 1,1 stage IIIA and 3 stage IIIB tumors. Lobectomy was performed in 8 patients and pneumonectomy in 2 patients. Nine patients underwent the operation under one-lung ventilation. A median period of preoperative administration of antibiotics was 6.2 days. The curative operation for lung cancer was performed in 3 patients and non-curative operation in 7 patients. Postoperative complications were pneumonia in 2, subcutaneous abscess in 2 and arrhythmia in a case of pneumonectomy. All non-curative patients died in 5 years, but two curative patients survived long time for 31 and 75 months, respectively. We performed urgent pulmonary resection for lung cancer patients to cure fatal pneumonia and cancer. There were no hospital death. Urgent pulmonary resection could prevent early death caused by fatal pneumonia by tumor itself.

Adenocarcinoma↗

PubMed1997

Intracellular viral localization in murine coxsackievirus-B3 myocarditis. Ultrastructural study by electron microscopic in situ hybridization.

Group B Coxsackieviruses are a common cause of myocarditis. To detect the viral genome and its localization in the myocardium, we examined C3H/He mice with Coxsackievirus B3 (CVB3) myocarditis on days 5, 8, and 14 after inoculation by the reverse transcriptase polymerase chain reaction and by in situ hybridization. Sense and antisense CVB3 RNA were detected in the myocardium of all mice up to day 14 by reverse transcriptase polymerase chain reaction. Light microscopic in situ hybridization with a cDNA probe for CVB3 showed clusters of positive signals in the areas of myocardial necrosis and cell infiltration. With electron microscopic in situ hybridization, CVB3 RNA was detected in the cytoplasm of cardiocytes, between the myofibrils, near the mitochondria, and in tubular or vesicular structures. Viral RNA was also detected in necrotic debris, in the cytoplasm of macrophages, and in the cytoplasm of interstitial fibroblasts. These findings suggest that CVB3 RNA is replicated in the cytoplasm of cardiocytes, transferred into tubular or vesicular structures, released into the interstitium, and phagocytosed by macrophages. Some positive signals were also detected in the cytoplasm of cardiocytes showing close contact with infiltrating lymphocytes, suggesting that the lymphocytes recognized virus-infected cardiocytes and caused cell-mediated immune cardiocyte damage.

Animals↗

PubMed1997

[Clinicopathological features of influenza myocarditis and pericarditis].

Myocarditis is a rare complication of influenza infection but is occasionally fatal. Recent application of percutaneous cardiopulmonary support and/or intraaortic balloon pumping to the serious case of viral myocarditis brought an good prognosis. We should recognize that the patient with viral infection such as influenza may have myocarditis and should make an early diagnosis for adequate treatment in time. To avoid misdiagnosis we must know characteristic symptoms and signs of cardiac involvement during influenza infection.

Humans↗

PubMed1996

Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation.

Plasma-soluble fibrin monomer (SFM) level in patients with disseminated intravascular coagulation (DIC) was significantly higher than the level in patients with pre-DIC or in non-DIC patients, and the level in patients with pre-DIC was significantly higher than that in non-DIC patients. There was no significant difference in plasma SFM levels among various diseases underlying DIC. Plasma SFM level in patients with good outcome was significantly decreased after treatment for DIC. The sensitivity of fibrin degradation products and platelet number was high for DIC, but not for pre-DIC. The sensitivity of thrombin-antithrombin III complex, plasmin-plasmin inhibitor complex, and SFM was high for both DIC and pre-DIC. The specificity of these markers was also high. Receiver operating characteristic analysis suggests that plasma SFM level could be the most useful marker for the diagnosis of both DIC and pre-DIC.

Amino Acid Sequence↗

PubMed1996

Protein C activation in NIDDM patients.

Enhanced activation of the clotting system has been recently implicated in the pathogenesis of vascular complications in patients with diabetes mellitus. Abnormalities of the anticoagulant system may constitute a potential trigger factor for the haemostatic activation observed in diabetic subjects. The current study aimed to evaluate anticoagulant activity in diabetic patients by assessing the plasma levels of activated protein C-protein C inhibitor complex; and by measuring the anticoagulant response to exogenous thrombomodulin. This study comprised 61 patients (34 men, 27 women) with non-insulin-dependent diabetes mellitus (NIDDM) of whom 22 showed microalbuminuria and 39 normoalbuminuria. Data obtained in 31 non-obese and non-diabetic subjects were available for comparison. The plasma levels of fibrinogen (p < 0.02), prothrombin fragment 1 + 2 (p < 0.05), fibrin monomer (p < 0.0001), protein C antigen (p < 0.005), total protein S antigen (p < 0.02), soluble thrombomodulin (p < 0.005) and soluble E-selectin (p < 0.005) were significantly higher in diabetic patients than in healthy subjects. The plasma level of activated protein C-protein C inhibitor complex (7.4 +/- 3.8 vs 3.0 +/- 0.4 pmol/l) was significantly higher (p < 0.0001) and the anticoagulant response to exogenous thrombomodulin (23.4 +/- 2.6 vs 35.3 +/- 3.0 ng/ml) was markedly lower (p = 0.005) in all diabetic patients than in healthy subjects. Cases with microalbuminuria presented low plasma levels of activated protein C-protein C inhibitor complex (5.5 +/- 0.6 vs 8.6 +/- 0.7 pmol/l, p < 0.05) and significantly decreased values of the anticoagulant response to exogenous thrombomodulin (16.5 +/- 2.9 vs 23.4 +/- 2.6%, p = 0.03) as compared to those with normoalbuminuria. The present study suggests that the hyper-coagulable state in NIDDM is associated with an increased activation of protein C but with a poor plasma reactivity to the anticoagulant effect of thrombomodulin.

Adult↗

PubMed1996

Molecular detection and differentiation of enteroviruses in endomyocardial biopsies and pericardial effusions from dilated cardiomyopathy and myocarditis.

Enteroviruses (EVs), especially group B coxsackieviruses, have been implicated in the pathogenesis of myocarditis and dilated cardiomyopathy (DCM). To determine whether a specific type of EV is present in DCM hearts, we examined the genotypes of EVs detected in endomyocardial biopsies and pericardial effusions by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Positive PCR results were obtained from biopsies in 6 (19 percent) of 31 patients with DCM, 5 (18 percent) of 28 with myocarditis, 5 (22 percent) of 23 with other cardiac diseases, and from pericardial effusions in 4 (57 percent) of 7 patients with pericarditis. SSCP profiles of most of the clinical samples were different and were not identical to any of the standard group B coxsackie viruses. Our findings suggest that EV genomes are involved in the myocardium of patients with various cardiac conditions and that a particular type of EV is not present in DCM hearts.

Adolescent↗

PubMed1996

Vasospastic angina in patients with systemic triglyceride storage disease with Jordans' anomaly and cardiomyopathy.

Vasospastic angina was demonstrated clinically and angiographically in a 54-year-old patient with systemic triglyceride storage disease and cardiomyopathy. He and his younger sister had been diagnosed in 1985 as having systemic triglyceride storage with Jordans' anomaly. In 1993, he began complaining of rest and effort chest pain in the morning, which was accompanied by ST depression by ECG. Sublingual nitroglycerine was effective for treating this pain. Intracoronary injection of acetylcholine induced severe coronary vasoconstriction in the left anterior descending artery. Left ventricular contraction was diffusely impaired. Deposits of numerous triglyceride droplets and a decrease in the density of myofibrils in cardiocytes were found in the specimens obtained by endomyocardial biopsy. The impaired left ventricular contraction may have been due to the changes in myocardial cells. His sister complained of a similar chest pain that was completely controlled by calcium channel antagonis. Thus, our cases demonstrated vasospastic angina associated with cardiomyopathy secondary to systemic triglyceride storage disease with Jordans' anomaly, though the causal relationship between these conditions remains unclear.

Adult↗

PubMed1996

[Plasma fibrin monitor level in DIC patients with a hematopoietic malignancy].

The Plasma level of soluble fibrin monomer (sFM) was measured in 218 patients with a hematopoietic malignancy. Of them, 198 were diagnosed with disseminates intravascular coagulation (DIC), 20 with Pre-DIC, and 20 with Non-DIC. Pre-DIC was retrospectively defined as the condition at least 1 week before the onset of DIC. The plasma levels of sFM, thrombin-anti-thrombin III complex (TAT), plasmin alpha 2-antiplasmin inhibitor complex (PIC), and FDP-D-dimer were significantly higher in patients with DIC than in those with Non-DIC. These levels were significantly higher in patients with Pre-DIC than in those with Non-DIC. Among these hemostatic parameters, the plasma sFM showed the highest sensitivity and specificity for DIC or Pre-DIC. These findings suggests that sFM is the most valuable marker hemostatic for the diagnosis of DIC and Pre-DIC.

Biomarkers↗

PubMed1996

Thoracoscopic treatment for spontaneous pneumothorax in patients over 50 years old: a comparison with younger patients.

The purpose of this study was to compare thoracoscopic treatment for spontaneous pneumothorax in patients over 50 years old (OG) and younger patients (YG). Thoracoscopic treatment was performed in both groups using the same patient selection criteria: persistence of an air leak after tube thoracostomy drainage, ipsilateral recurrence, and bilateral pneumothoraces. Thoracoscopic treatment was performed in nine older patients (OG) over a two-year period. Their ages ranged from 50 to 81 years (average: 66 years). The mean operative time, postoperative drainage period, and hospital stay after surgery were 120 min, 6.3 days, and 10.7 days, respectively. In the YG, these indices were 71 min, 1.5 days, and 5.3 days, respectively. Each factor was significantly prolonged in the OG (p < 0.05). However, there were no major perioperative complications or recurrences 3-24 months after surgery in either group. Thus, thoracoscopic surgery is also effective in the treatment of spontaneous pneumothorax in patients over 50 years old.

Age Factors↗

PubMed1996

Lobectomy by video-assisted thoracic surgery for a hilar bronchial carcinoid tumor.

A 45-year-old man with bronchial carcinoid arising from the subsegmental middle-lobe bronchus was treated by video-assisted thoracic surgery. Lobectomy with mediastinal and hilar lymph node sampling was successfully performed in this patient. To obtain a tumor-free surgical margin on the middle-lobe bronchus, the interlobar pulmonary artery was retracted posteriorly, the middle-lobe bronchus anteriorly. The bronchus was then stapled and transected.

Bronchial Neoplasms↗

PubMed1994

Long-term survival in a patient with malignant carcinoid treated with high-dose octreotide.

Octreotide acetate, a long-acting somatostatin analogue, is effective in controlling and markedly reducing the symptoms of carcinoid crisis. We report a patient with carcinoid syndrome with prolonged survival for 4.5 years with high dose octreotide therapy and survived for 7.5 years after the first flushing, in spite of episodes of severe carcinoid crisis. Dose escalation was required in order to control carcinoid symptoms, and the final dosage was 5,950 micrograms/day. Although administration of such a high dosage of octreotide has never been reported before, we found that octreotide could be used at this dosage safely without inducing serious side effects, and probably prolonged the patient's survival. Our experience with this case indicates that octreotide acetate is an effective drug in controlling carcinoid crisis and prolonging survival without serious side effects.

Antineoplastic Combined Chemotherapy Protocols↗