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Biomedical subjects

H Sekiguchi

Publications and source records attributed to H Sekiguchi.

At least 55 records · Page 3Linked to original sources

Toxicity study of a rubber antioxidant, 2-mercaptobenzimidazole, by repeated oral administration to rats.

The chemical structure of 2-mercaptobenzimidazole (2-MBI), which is widely used as a rubber antioxidant, is partially similar to those of thiourea (TU) and ethylenethiourea (ETU), both potent thyrotoxic compounds. In order to determine the oral toxicity of 2-MBI, a 28-day repeated dose toxicity study in Wistar rats followed by observation over a 14-day recovery period was conducted at dose levels of 2, 10 and 50 mg/kg 2-MBI administered by gavage. No toxic deaths occurred due to 2-MBI treatment. Decreases of body weight gain and food consumption in the 50 mg/kg dose group were observed during the second half of the treatment period. In addition, hematological examination and serum biochemical tests revealed decreased white blood cells and hemoglobin and increased serum urea nitrogen, cholesterol, phospholipid, gamma-glutamyl transpeptidase and the Na+/K+ ratio in the 50 mg/kg dose group. Marked thyroid enlargement (to 10 fold the control weight), histopathologically associated with diffuse hyperplasia of follicles with decreased colloid and thickening of the fibrous capsule, was found. Reduction in thymus weight was also observed in a dose-dependent manner, without significant histopathological alteration. The non-observed effect level (NOEL) of 2-MBI in this gavage study was found to be less than 2 mg/kg/day based on the significant decrease in thymus weight in the 2 mg/kg 2-MBI treatment group. In an ancillary study, measurement of serum levels of T3, T4 and TSH, and thyroid weight after gavage treatment with 0.15 and 0.3 mmol/kg of three antithyroid compounds for 14 days revealed a more potent antithyroid effect for 2-MBI than for TU or ETU.

Administration, Oral↗

Induction of torsades de pointes by dobutamine infusion in a patient with idiopathic long QT syndrome.

We used a provocative test with dobutamine infusion to diagnose long QT syndrome (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate of 10 microg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes developed. In 5 control subjects the QTc did not change significantly during low-dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may be useful for evaluation of prolongation of the QT interval and abnormal TU complexes in patients in whom LQTS is suspected.

Adolescent↗

PCR detection of the human amelogenin gene and its application to the diagnosis of amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a disease in which there is a defect in the formation of the tooth enamel of deciduous and permanent teeth. In an attempt to clarify the genetic abnormality in patients with amelogenesis imperfecta, we have been investigating their amelogenin gene. In this study, we have determined the nucleotide sequences of regions of the intron 1 and intron 2 of the X and Y human amelogenin genes (AMGX, AMGY) for the first time, and established a polymerase chain reaction (PCR) protocol to amplify six exons of AMGX and AMGY for the diagnosis of amelogenesis imperfecta, because previous studies have shown that some of the AI patients have such mutations. This study gives us an easy and fast method to analyze protein encoding regions of the amelogenin genes. The applications of this method will give us better insight into classifying AI, followed by understanding of the cause of the disease.

Amelogenesis Imperfecta↗

Effect of mitral valvuloplasty in mitral stenosis on coagulation activity.

We investigated the plasma levels of molecular markers for the status of thrombin generation and fibrinolysis in patients with mitral stenosis before and after percutaneous mitral valvuloplasty. Our results show that percutaneous mitral valvuloplasty results in decreased coagulation activity, suggesting that percutaneous mitral valvuloplasty is also useful for prevention of systemic embolism in patients with mitral stenosis.

Blood Coagulation↗

Lack of association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and vasospastic angina.

BACKGROUND AND HYPOTHESIS: It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary atherosclerosis and myocardial infarction, but its relation to vasospastic angina has not been fully proven. In the present study, we investigated the possible relationship between the ACE I/D genotype and vasospastic angina. METHODS: We explored the distribution of the ACE genotype in 20 patients with vasospastic angina without fixed coronary artery stenosis, 55 angina patients with fixed coronary artery stenosis, and 30 control subjects without coronary artery disease. RESULTS: The frequency of the DD genotype in patients with vasospastic angina (DD: 30.0%, ID: 20.0%, II: 50.0%) did not differ from that in the control subjects (DD: 23.3%, ID: 26.7%, II: 50.0%), while the frequency in patients with coronary artery stenosis (DD: 43.7%, ID: 21.8%, II: 34.5%) was significantly higher than that in the control subjects. The frequency of the D allele also did not differ between patients with vasospastic angina (0.40) and control subjects (0.37), while the frequency was significantly higher in patients with coronary artery stenosis (0.55). CONCLUSIONS: These findings suggest that the ACE DD genotype is a potent genetic risk factor for organic coronary artery disease, while it confers no appreciable increase in risk of vasospastic angina. These results also suggest the diversity of the pathogenesis of vascular lesions in these two types of coronary artery disease.

Aged↗

Direct and rapid detection of porcine epidemic diarrhea virus by RT-PCR.

To establish a practical method for detecting porcine epidemic diarrhea virus (PEDV), the use of primers derived from sequences that amplify the M protein genes of PEDV in a RT-PCR detection system was investigated. Primers were designed to amplify a 854-bp fragment by RT-PCR. This reaction was specific to the PEDV RNA but not to that of other viral genera tested. In experiments with mixtures of PEDV and either small intestine or fecal homogenates, this method could detect efficiently the PEDV RNA from samples containing very low numbers of virus (100 TCID50/sample) within 8 h. With specimens collected from swine breeding farms with the diarrhoeal disease, the PEDV RNA was detected in four intestine specimens out of 11 specimens. The result was in close agreement with the results of virus isolation and streptavidin-biotin technique for detecting PEDV and its antigens, suggesting that the RT-PCR assay would be useful method for practical application.

Animals↗

Expression of MRP and mdr1 in human gastrointestinal cancer cell lines: a correlation with resistance against doxorubicin.

The mRNA expression of mdr1 and MRP, each of which codes for a transport protein belonging to ATP-binding cassette superfamily and are reported to be responsible for multidrug resistance phenotype, were semi-quantified by RT-PCR in a panel of gastrointestinal cancer cell lines. Although the expression of MRP was predominant in esophageal cancer cell lines, expression of either or both of the genes was detected in all the cell lines tested. Expression of these two genes added together correlated significantly with chemosensitivity against doxorubicin, implicating that expression of both genes should be evaluated in the future analysis of multidrug resistance phenotype. The ID50 values for pirarubicin, although generally lower than the values for doxorubicin, correlated well with the latter, suggesting that the similar phenotype as that for doxorubicin might be responsible for drug resistance against this semisynthetic anthracycline glycoside.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Preoperative embolization of gastric arteries for esophageal cancer.

BACKGROUND: We developed a novel treatment of preoperative embolization therapy in an attempt to prevent anastomotic leakage after esophageal resection. We report the results of this new treatment. METHODS: Preoperative embolization therapy (PET) was performed in 24 cases of esophageal carcinoma. The femoral artery was punctured, and celiac angiography was performed. The left gastric artery and splenic artery underwent embolization. The right gastric artery then underwent embolization at a site beyond the second or third branch to the gastric wall. With a laser flow meter the stomach tissue blood flow was measured before and after construction of the gastric tube, and the change in blood flow was compared. RESULTS: The average decrease in gastric blood flow was 23% in patients with PET and 65% in patients without PET. Twenty-one (88%) of 24 cases maintained more than 50% tissue blood flow in patients with PET and in 1 (8%) of 12 in patients without PET (p < 0.001 by t test). No serious complications occurred. CONCLUSIONS: Preoperative embolization therapy is a safe and uncomplicated technique, and tissue blood flow in the stomach was better preserved. This new technique is expected to reduce the frequency of anastomotic leakage after esophageal operation.

Adult↗

Efficacy of Cafon gel on cutaneous infection with herpes simplex virus (HSV)-2 and acyclovir-resistant HSV in mice.

Caffeine is known to inhibit replication of herpes simplex virus (HSV)-1 and the therapeutic efficacy of caffeine (Cafon) gel has been shown in a mouse model cutaneously infected with HSV-1. In this study we examined the inhibitory effect of caffeine on infection with HSV-2 and acyclovir-resistant HSV-1 strains, thymidine kinase (TK)-deficient and phosphonoacetic acid (PAA)-resistant HSV-1 in vitro and in vivo. Caffeine inhibited plaque formation of HSV-2 and acyclovir-resistant HSV-1 strains and their EC50 values ranged from 0.42 to 1.11 mg/ml. Topical treatment with Cafon gel was significantly effective in retarding the development of skin lesions caused by cutaneous infection with HSV-2 and PAA-resistant HSV-1 and in reducing the virus yield of the skin infected with TK-deficient HSV-1. The results suggested that Cafon gel would be useful for the topical treatment of cutaneous infection with HSV-2 and acyclovir-resistant HSV strains.

Acyclovir↗

Guide wire-induced coronary artery spasm during percutaneous transluminal coronary angioplasty. A case report.

Coronary artery spasm induced by a guide wire is a very rare complication of percutaneous transluminal coronary angioplasty (PTCA). The authors describe a patient who developed coronary vasoconstriction distal to the dilated lesion during PTCA, which was refractory to intracoronary nitroglycerin and intravenous calcium antagonist injection and balloon angioplasty but responded promptly and completely to withdrawal of the guide wire from the coronary artery, suggesting that the spasm had been induced by the guide wire.

Aged↗

[Influence of KU-1257 on the recurrence and relapse of acetic acid-induced chronic gastric ulcers in rats].

The influence of KU-1257 on the recurrence and relapse of acetic acid ulcers in rats was investigated grossly and histologically in comparison with that of cimetidine. The ulcer was induced by topical application of glacial acetic acid at the junction of the corpus and antrum on the anterior wall of the stomach. The drug was administered from the 5th to the 153rd day after the ulcer induction and then discontinued to the 238th day. The healing rates of the control groups (control) rose until the 119th day after the ulcer induction, followed by ups and downs. The quality of healing in the regenerated mucosa and the granulation tissue of the healed ulcer was poor, resulting in the recurrence and relapse of ulcers. The recurrence and relapse of ulcers also occurred in the cimetidine groups (CIM). On the other hand, the KU-1257 groups (KU-1257) showed much lower recurrence and relapse rates of ulcers than the control and CIM groups. Moreover, KU-1257, unlike CIM, improved the quality of ulcer healing throughout the period of its administration and even after it was discontinued. These results suggest that KU-1257 improves the quality of ulcer healing, and this may contribute to the low recurrence and relapse rates of ulcers.

Acetates↗

Prediction of hemodynamic conditions by noninvasive arterial tonometry in mitral stenosis.

To predict the hemodynamic conditions in patients with mitral stenosis (MS), continuous blood pressure responses were monitored noninvasively at the bedside by arterial tonometry during the Valsalva maneuver in 18 MS patients aged 54.2 +/- 9.1 (40 approximately 77) years (6 men, 12 women). Two indices during the Valsalva maneuver (blood pressure decline value at phase III (BPdec) and subsequent blood pressure overshoot value at phase IV (BPov)) were compared with hemodynamic data obtained by the cardiac catheterization method, and the correlations between the changes in these parameters were examined. In these 18 patients, BPdec showed a significant negative correlation with the mean diastolic pressure gradient between the left atrium and left ventricle and showed a significant negative correlation with pulmonary capillary wedge pressure (PCWP) (r = - 0.62, p < 0.01, r = - 0.53, p < 0.05, respectively). Mitral valve area (MVA) showed a significant positive correlation with BPdec (r = + 0.63, p < 0.01). Similarly, BPov showed a significant positive correlation with cardiac output (CO), cardiac index (CI) and MVA (r = + 0.60, p < 0.01, r = + 0.64, p < 0.01, r = + 0.65, p < 0.01, respectively). Thus, continuous monitoring of blood pressure by arterial tonometry during the Valsalva maneuver is useful for predicting the hemodynamic conditions in patients with MS.

Adult↗

Endothelin-1 production in coronary circulation in a new canine model of coronary thrombosis.

OBJECTIVE: The purpose of this study was to investigate whether endogenous endothelin-1 (ET-1) production in coronary circulation is associated with acute coronary thrombotic events in vivo. To achieve this goal, we have designed a new experimental canine model of coronary thrombosis. METHODS: In vivo occlusive thrombus was induced by the intracoronary application of radiofrequency energy (660 kHz, 50 W) in closed-chest dogs. Pathological and immunohistochemical examinations of thrombosed coronary artery were performed. In 12 dogs, plasminogen activator was administered intravenously and serial measurements of ET-1, thromboxane B2 (TXB2) and thrombin-antithrombin III complex (TAT) levels in plasma from the coronary sinus, aortic root and inferior vena cava were examined. RESULTS: Occlusive platelet-rich thrombi were attached to the deeply injured intimal surface. TAT and TXB2 increased rapidly soon after the intimal injury and declined after successful thrombolysis. In contrast, ET-1 in the coronary sinus was elevated after reperfusion and was significantly higher than in the aorta. Net ET-1 production in the coronary circulation showed a significant positive correlation with the peak TAT levels (r = 0.69, P < 0.05), but not with TXB2 or total occlusion time as an index of ischemic severity. CONCLUSIONS: Deep intimal injury leads to occlusive coronary thrombus. Thrombus formation and its subsequent lysis is associated with the activation and deactivation, respectively, of the coagulation cascade and platelets. Thrombin generation may stimulate ET-1 production in the coronary endothelium in acute coronary thrombotic events.

Acute Disease↗

Preoperative intra-aortic ultrasonography to determine resectability in advanced oesophageal cancer.

This study was designed to evaluate the effectiveness of intra-aortic ultrasonography in the preoperative diagnosis of aortic wall invasion by oesophageal cancer. Twenty-four patients with advanced oesophageal cancer underwent the procedure, and aortic invasion was found in seven. In three of these seven patients, the invasion was diagnosed to be limited to the aortic adventitia, enabling preoperative prediction of the resectability of the tumour. The contact angle of the tumour in relation to the descending aorta was more than 90 degrees in six patients, and aortic invasion to all layers was visualized in four by intra-aortic ultrasonography. On the other hand, aortic invasion to the adventitia was found in three of 14 patients in whom the contact angle was less than 90 degrees. Intra-aortic ultrasonography provides important information to help determine the resectability of advanced oesophageal cancer.

Adult↗

Expression of leukocyte chemotactic cytokines in myocardial tissue.

Cytotoxic action of leukocytes may be involved in the pathogenesis of inflammatory heart muscle disorders. We investigated the expression of rat leukocyte chemotactic cytokines--cytokine induced neutrophil chemoattractant (CINC) and JE--in cultured neonatal rat cardiac myocytes; CINC belongs to the interleukin 8 (IL-8) family and JE is a homologue of human monocyte chemoattractant protein 1 (MCP-1). In Northern blot analysis, CINC and JE transcripts were not clearly observed in unstimulated rat cardiac myocytes. However, their expression was clearly observed after exposure to tumour necrosis factor-alpha (TNF-alpha; 100 U/ml) for 2-6 h. We then evaluated IL-8 and MCP-1 mRNA expression in human endomyocardial biopsy specimens from seven patients with idiopathic dilated cardiomyopathy by polymerase chain reaction analysis. Both IL-8 and MCP-1 mRNA transcripts were recognized in all patients studied. These results show for the first time that leukocyte chemotactic cytokines, IL-8 and MCP-1, are expressed in myocardial tissue, which might contribute to the pathogenesis of inflammatory heart muscle disorders.

Animals↗

Use of the double-stapling technique in esophageal surgery.

This study was conducted to examine the effectiveness of the double-stapling technique (DST) for performing esophageal anastomoses. A total of 17 patients, 10 with esophageal cancer and 7 with gastric cancer, underwent esophageal anastomosis employing this technique. Of the ten patients who underwent esophageal operations, eight received esophageal-gastric tube anastomosis, one esophageal-colon and colon-residual stomach anastomosis, and one pharyngeal-gastric tube anastomosis, while all seven of the patients who underwent operations for gastric cancer received esophagojejunostomy. Thus, a total of 18 anastomoses were performed. No problems were encountered during the anastomoses, and no leakage occurred in any of the patients. Thus, we conclude that DST is a safe and easy technique for performing esophageal anastomosis, especially intrathoracic or intramediastinal anastomoses.

Anastomosis, Surgical↗

Coagulation activity is increased in the left atrium of patients with mitral stenosis.

OBJECTIVES: This study investigated the hemostatic status of the right and left atria in patients with mitral stenosis. BACKGROUND: Systemic thromboembolism is a serious major complication in patients with mitral stenosis. However, the pathogenesis of thromboembolism in mitral stenosis is not fully understood. METHODS: We determined the plasma levels of biochemical markers for platelet activity (platelet factor 4 and beta-thromboglobulin) and status of thrombin generation (fibrinopeptide A and thrombin-antithrombin III complex) and fibrinolysis (D-dimer and plasmin-alpha 2-plasmin inhibitor complex) in specimens of blood obtained from the peripheral vein and right and left atria of 12 consecutive patients with mitral stenosis who were undergoing percutaneous mitral valvuloplasty. RESULTS: Plasma levels of platelet factor 4, beta-thromboglobulin, D-dimer and plasmin-alpha 2-plasmin inhibitor complex in the patients did not differ significantly between the right and left atria, whereas levels of fibrinopeptide A and thrombin-antithrombin III complex in the left atrium were significantly higher than those in the right atrium (fibrinopeptide A in the left and right atria 19.35 +/- 4.64 and 6.31 +/- 0.75 ng/ml [mean +/- SE], respectively, p < 0.02; thrombin-antithrombin III complex in the left and right atria 11.45 +/- 2.29 and 3.98 +/- 0.60 ng/ml, respectively, p < 0.01). Levels of fibrinopeptide A and thrombin-antithrombin III complex in the left atrium did not correlate with mean transmitral gradient, dimension of the left atrium or reciprocal of the mitral valve area. Peripheral blood plasma levels of von Willebrand factor antigen were significantly higher in the patients than in an age-matched control group of normal subjects (168 +/- 25% and 99 +/- 7%, respectively, p < 0.05) but showed no difference in the peripheral blood and right and left atria of the patients. CONCLUSIONS: The coagulation system is activated in the left atrium of patients with mitral stenosis even during anticoagulation.

Adult↗

Multiple saccular aneurysm formation in a patient with bilateral coronary artery fistula: a case report and review of the literature.

We describe a case of bilateral coronary artery fistula originating from the left anterior descending and right coronary arteries which showed multiple saccular aneurysm formation. Although saccular aneurysm formation in patients with bilateral coronary artery fistula is extremely rare, only 3 similar cases having been reported before, it shows two distinctive features upon coronary angiography: multiplicity and origin in the left fistulous coronary artery.

Adult↗