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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 307 records · Page 17Linked to original sources

Interleukin-12 augments cytolytic activity of peripheral and decidual lymphocytes against choriocarcinoma cell lines and primary culture human placental trophoblasts.

PROBLEM: Human trophoblasts are tolerant to the maternal immune system, but susceptible to interleukin (IL)-2-activated lymphocytes. IL-12 is also a key cytokine in the induction of cytotoxic responses. We administered IL-12 to peripheral blood lymphocytes (PBLs) and to decidual lymphocytes (DLs) and studied resulting cytotoxicity against trophoblasts. METHOD OF STUDY: PBLs and DLs were stimulated with rIL-2 and/or rIL-12 for 48 hr in vitro. Cytotoxicity against the choriocarcinoma cell line JEG-3, JAR, and primary culture trophoblasts were examined by LDH release assay. The proliferative response was estimated by MTT assay. Expression of cytotoxic factors was studied by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Whereas IL-12 alone produced a modest enhancement in cytotoxicity of PBLs and DLs, the combination of IL-2 and IL-12 was most effective in trophoblast cell lysis. IL-12 enhanced the mRNA expression of T-cell specific serine protease (TSP, granzyme B) and FasL in DLs, but the expression of perforin was unchanged. Expression of these cytotoxic factors in PBLs was up-regulated by IL-12. CONCLUSION: Our findings indicate critical roles of IL-12 in the activation of maternal lymphocytes, which could possibly result in pregnancy failure syndromes.

Adult↗

Prevalence of hepatitis G virus in liver disease.

The prevalence of hepatitis G virus (HGV) in liver disease of non-A, -B, -C viral hepatitis, hepatitis B and hepatitis C was determined. Two of 44 patients (4.5%) with liver injury without any hepatitis A, B or C marker were positive for HGV. One of five cases of hepatocellular carcinoma was positive for HGV. One of three cases with fulminant hepatitis was positive for HGV. This case was negative at the onset of fulminant hepatitis and became positive after plasmapheresis. No patient with acute (n=8) or chronic (n=5) hepatitis or liver cirrhosis (n=8) was positive for HGV in non-A, -B, -C liver disease. One of 30 patients with various HBV-positive liver diseases and nine (17.3) of 52 patients with type C liver disease were positive for HGV. In patients with hepatitis C, four (28.6%) of 14 HGV-co-infected patients were complicated with diabetes mellitus compared with four (10.5%) of 38 single hepatitis C virus (HCV)-infected patients (not significant). In 12 HGV-positive patients, eight of 10 (80%) had a history of blood transfusion. In HCV-positive patients, co-infection with HGV was not a risk factor in patients with diabetes mellitus as a complication. HGV appeared to cause non-A, -B, -C hepatitis rarely, and its main route of infection was blood transfusion.

Adolescent↗

Gene expression in primary, metastatic and recurrent lesions of endometrial cancer.

Seventeen patients with endometrial cancer were studied. Tissues of primary (P) and metastatic (M) lesions were obtained from 8 patients and complete sets of P, M and Recurrent (R) lesions were obtained from 9 patients during a follow-up period of 1-10 years. Expressions of estrogen receptors, progesterone receptors, multidrug resistance protein-1, multidrug resistance-related protein, c-erbB-2, membrane-type metalloproteinase, human telomerase RNA, human telomerase reverse transcriptase RNA, E-cadherin and autocrine motility factor receptor were studied by RT-PCR. Also, telomeric restriction fragment length (TRFL) and microsatellite instability were determined between P, M and R. The results indicate that there are significant differences in the gene expression frequency during tumor progression. The mismatch rate ranged from 0 to 47.1% between P and M and from 14.3% to 66.7% between P and R, respectively. The TRFL analysis showed a marked reduction in P and M (P vs. M: 8.2 +/- 0.9 vs. 5.6 +/- 0.4 kb, mean +/-SEM, n = 9, p = 0.002 by paired Student's t test). The length further decreased in R (P vs. R: 8.2 +/- 0.9 vs. 3.2 +/- 0.7, p = 0.01, M vs. R: 5.6 +/- 0.4 vs. 3.2 +/- 0.7, p = 0.005). The genomic instability/replication error was tested by AluI arbitrary primed polymerase chain reaction (AP-PCR). Five out of 17 patients showed an altered replication error pattern (29.4%). The mean number of abnormal AluI AP-PCR patterns in M and R compared to the P was 1.5 (M) and 4 (R). The difference between the P and R was statistically significant (p < 0.04). The present data indicate that biological behavior of cancer cells in P, M and R may differ significantly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The effect of hyaluronic acid-carboxymethylcellulose in reducing adhesion reformation in rabbits.

The effect of hyaluronic acid-carboxymethylcellulose film (Seprafilm) in reducing postoperative adhesion formation was examined in a rabbit induced-adhesion model. During laparotomy, the ileocaecal region was mechanically and chemically abraded to induce lesions. After a 28-day recovery period, adhesions were lysed by microsurgery and Seprafilm was applied to the lysed lesion in 10 rabbits and six rabbits received physiological saline. A third laparotomy was performed 10-14 days later and the area of adhesion reformation was compared to that found prior to application of test materials. The area of adhesion reformation with Seprafilm decreased to (mean +/- standard deviation) 11.71 +/- 10.97% of the originally lysed lesion and, the area was significantly reduced compared with controls treated with physiological saline. These results suggest that the use of Seprafilm may be a valuable new anti-adhesion material for abdominal or pelvic surgery and may be superior to existing anti-adhesion materials and techniques.

Animals↗

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗

[Determination of sennoside A and sennoside B in formulation using capillary electrophoresis].

The determination of sennoside A (SA) and sennoside B (SB) by capillary zone electrophoresis was developed. The separation of SA and SB was performed in 100 mM of the 3-[cyclohexylamino]-1-propanesulfonic acid (CAPS) buffer (pH 10.0), and the migration time of SA and SB was found to be both less than 7 min. This method was applied to the analyses of seven commercial formulations containing SA and SB without previous treatment. The statistical comparison of the results obtained from both capillary electrophoresis and HPLC methods revealed an absolute correlation.

Anthraquinones↗

Effect of insulin resistance on the endothelial vasomotor function of the coronary artery of nondiabetic patients.

Attention has been paid to the relationship between insulin resistance and coronary artery disease. The present study investigated the relationship between insulin resistance and the endothelial vasomotor function of the coronary artery of nondiabetic patients with chest pain and a positive exercise tolerance test. Twenty-five nondiabetic patients with chest pain were included. Patients with a steady state plasma glucose (SSPG) level of greater than or equal to 135 mg/dl were placed in the insulin resistant (IR) group, and those with a SSPG level less than 135 mg/dl were placed in the noninsulin resistant (NIR) group. The effect of acetylcholine, papaverine, and isosorbide dinitrate on the vasomotor response of the coronary endothelium was studied. The percent change in diameter of the coronary artery after injection of acetylcholine (20 microg ml(-1) min(-1)) was 84+/-17% in the IR group, and 109+/-18% in the NIR group. The difference in the degree of the vasodilative response is statistically significant (p<0.01). The percent change in coronary flow velocity after injection of acetylcholine (20 microg ml(-1) min(-1)) in the IR group was 120+/-67%, whereas that in the NIR group was 256+/-58%; the increase in coronary artery flow velocity of the IR group was significantly smaller than that of the NIR group (p<0.01). Nondiabetic patients with insulin resistance have endothelial vasomotor dysfunction, which raises an important question as to whether nondiabetic patients with insulin resistance should be treated to prevent the development of coronary heart disease.

Acetylcholine↗

Cone-beam CT angiography of the thorax: an experimental study.

The authors recently developed a cone-beam computed tomography (CT) scanner and this report presents their evaluation of its potential for thoracic vascular imaging. An X-ray tube and a video-fluoroscopic system were rotated around the objects and 360 projected images were collected in a 12-s scan. Each image was digitized and a 3 dimensional (D) image (256x256x256 voxel volume with a voxel dimension of 0.9x0.9x0.9 mm) was reconstructed. Two different 3D-CT angiographies were investigated in 2 pigs: right atriography and thoracic aortography. Each pig was anesthetized, mechanically ventilated and positioned within the scanner. Contrast agent was infused through the right atrium or the aortic root at a rate of 3 ml/s during the scan. The right atriography scan clearly delineated the anatomy of the pulmonary artery, heart chambers and thoracic aorta. The thoracic aortography scan also clearly delineated the aortic anatomy including the internal thoracic and intercostal arteries. In conclusion, cone-beam CT angiography is potentially useful for thoracic vascular imaging.

Angiography↗

[Microcirculation in the myocardium].

The coronary artery supplies the arterial blood that contains oxygen and nutrients for the myocardial tissue to produce high-energy phosphates aerobically. The left anterior descending and circumflex coronary arteries run on the epicardial surface of the left ventricle, turn toward the endocardium at a right angle, and nourish the tissues of the subendocardinal layers with the arterial blood. Cessation of coronary blood flow makes the myocardium ischemic. The endocardium is particularly susceptible to ischemia because the arteries that run to the endocardium are pressed due to extravascular compression during every systole. Coronary vasodilators are still used as anti-anginal drugs. However, a potent coronary vasodilator may cause coronary-steal and thereby worsen the ischemia-induced myocardial injury. We will demonstrate changes in the microcirculation of the ischemic myocardium caused by coronary vasodilators and demonstrate that a coronary vasodilator is not always effective on the ischemic myocardium.

Coronary Vessels↗

[Detection of drug-drug interaction by ESR spectroscopy].

Vitamin C (sodium ascorbate), gallic acid and dopamine induced apoptosis (characterized by internucleosomal DNA cleavage, nuclear fragmentation, chromatin condensation near nuclear membrane and loss of cell surface microvilli) in human promyelocytic leukemic HL-60 cells. ESR spectroscopy demonstrated the connection between the radical intensity and apoptosis-inducing activity of derivatives of these compounds. When vitamin C and gallic acid were mixed together, the radical intensity and cytotoxic activity of gallic acid was completely scavenged by one or two orders lower concentrations of vitamin C, suggesting the predominant action of vitamin C over gallic acid. When vitamin C and dopamine were mixed together, their radical intensity and apoptosis-inducing activity counteracted with each other. On the other hand, lignins significantly enhanced both the radical intensity and apoptosis-inducing activity of vitamin C. ESR spectroscopy might be applicable for the detection of drug-drug interaction.

Apoptosis↗

[Are all HMG-CoA reductase inhibitors protective against ischemic heart disease?].

Effects of pravastatin, simvastatin, atorvastatin, fluvastatin and cerivastatin on myocardial contractile dysfunction during reperfusion after brief ischemia were examined in dogs. Pretreatment of the dog with lipophilic HMG-CoA reductase inhibitors for 3 weeks, simvastatin (2 mg/kg/day), atorvastatin (2 mg/kg/day), fluvastatin (4 mg/kg/day), and cerivastatin (40 micrograms/kg/day) worsened recovery of myocardial contraction during reperfusion after brief ischemia in association with reduced myocardial ATP level. A hydrophilic HMG-CoA reductase inhibitor, pravastatin (2 and 4 mg/kg/day), did not affect the recovery of myocardial contractile function and ATP level during reperfusion following ischemia. The lipophilic inhibitors may enter the myocardial cell, inhibit ubiquinone biosynthesis, and depress ATP generation in mitochondria, leading to worsening of the myocardial stunning after reperfusion subsequent to ischemia.

Adenosine Triphosphate↗

Similarity and dissimilarity in mode and mechanism of action between YT-146, a selective adenosine receptor A2 agonist, and adenosine in isolated canine hearts.

To elucidate the differences in mode and mechanism of action between YT-146, a highly selective adenosine A2 receptor agonist, and adenosine, we compared their effects on coronary circulation and myocardium and modifications of these effects by glibenclamide, a blocker of ATP-sensitive potassium (K) channels, in three kinds of isolated, blood-perfused canine heart preparations. YT-146 and adenosine were injected i.a. In all preparations both YT-146 and adenosine increased coronary blood flow and in this respect YT-146 was about 5 times as potent as adenosine. The increase in blood flow caused by adenosine was transient, whereas that produced by YT-146 was biphasic; the transient increase was followed by a sustained one. In isolated, blood-perfused sinoatrial (SA) node preparations, YT-146 failed to affect sinus rate, whereas adenosine reduced sinus rate by about 38% at its maximum effect. In isolated, blood-perfused atrioventricular (AV) node preparations, when injected into the artery supplying the AV node, YT-146 exerted no effect on AV conduction time, whereas adenosine prolonged AV conduction time by about 17% at the maximum effect. In isolated, blood-perfused papillary muscle preparations, the force of contraction was affected by neither YT-146 nor adenosine. In the same preparations the effect of YT-146 in increasing coronary blood flow was antagonized by glibenclamide in such a manner that the maximum increase was suppressed, but that of adenosine was not. Reactive hyperemia induced by ischemia for 30 seconds was not affected by glibenclamide. These results suggest that although both YT-146 and adenosine produce an increase in coronary blood flow via adenosine A2 receptors, the opening of ATP- or glibenclamide-sensitive K channels is involved in the action of the former, but scarcely in the action of the latter. The opening of ATP- or glibenclamide-sensitive K-channels is less likely involved in reactive hyperemia.

Adenosine↗

Clinicopathological study on liver dysfunction in measles.

We analyzed the clinical course of eight patients with liver dysfunction in measles. All of the patients showed an elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH), but no jaundice. These levels returned to normal about 3 weeks after the onset of the rash. A percutaneous liver biopsy was done in two cases. Histological examination showed slight necrosis of liver cells but no significant changes in portal area. On electron microscopy, virus particles were not detected. We detected measles virus RNA in the liver specimen by RT-PCR, which suggests that the measles virus affects liver cells directly in measles.

Adolescent↗

Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia.

OBJECTIVE: In an attempt to investigate the prophylactic effect of a thromboxane A2 (TXA2) synthetase inhibitor on pregnant women with a high risk of preeclampsia, the following clinical study was undertaken. METHODS: Forty pregnant women were randomly allocated to control or treatment groups. Ozagrel Hydrochloride (400 mg/day, orally) and placebo were started at 20 weeks of gestation and continued until delivery. RESULTS: Seventeen of 20 (85%) women in the control group developed preeclampsia, whereas 9 of 20 (45%) in the treatment group developed preeclampsia. Ozagrel Hydrochloride significantly (p < 0.01) reduced the occurrence of preeclampsia, and the incidence of both hypertension (p < 0.05) and proteinuria (p < 0.01) was significantly less in the treatment group compared with the control group. One month after administration, the mean plasma concentration of TXB2, a metabolite of TXA2, was significantly decreased (p < 0.01) to 62.4 +/- 13.6%, whereas that of 6-keto prostaglandin F1 alpha, a metabolite of PGI2, was significantly increased (p < 0.01) to 206.7 +/- 52.8%. There were no maternal or fetal side effects observed. CONCLUSIONS: It seems likely that Ozagrel Hydrochloride could be used for the prevention of preeclampsia in high-risk pregnant women.

Administration, Oral↗

[Superior vena cava reconstruction combined with resection of mediastinal-pulmonary malignant tumors].

From 1988 to 1997, we experienced 5 cases of the superior vena cava (SVC) replacement with expanded polytetrafluoroethylene (ePTFE) grafts combined with resection of mediastinal or pulmonary malignant tumors. Two patients had lung cancer and three had invasive thymoma. Resection and reconstruction of the superior vena cava (SVC) were performed by application of a bypass graft between the innominate vein and the right atrium in two cases and a temporary bypass using a heparin-coated tube in three cases. Except in one patient who died of acute respiratory failure, no complication or occlusive symptom were observed postoperatively. Two patients remain healthy for 5 years 4 months and 2 years 7 months after operation. Three died 9 years, 5 months, and 110 days after operation respectively. In conclusion, ePTFE graft replacement or patch angioplasty of the SVC should be part of planning and execution of radical excision with curative intent of mediastinal or pulmonary malignant tumors.

Adult↗

[Antimicrobial resistance testing of H. pylori epsilometer test and disk diffusion test].

The resistance of Helicobacter pylori to antibiotics leaves great influence on treatment outcome. Routine antimicrobial susceptibility testing of H. pylori should be a simple, inexpensive and standardized method to be adopted. Agar and broth dilution techniques are difficult to perform and not practical. E-test and disk diffusion methods have the advantage of allowing the visualization of resistant subpopulations of bacteria within zones of inhibitions. We studied the susceptibility results of 246 H. pylori isolates against metronidazole and clarithromycin using E-test and disk diffusion test. The results of disk diffusion test were well correlated with these of E-test. Our results showed that disk method is cost effective and simple for the screening for antimicrobial resistance of H. pylori.

Clarithromycin↗

[Changes in the severity of atrophic gastritis after Helicobacter pylori eradication].

There is a diversity of opinions as to whether Helicobacter pylori eradication leads to the improvement or regression of atrophic gastritis and intestinal metaplasia (IM), which are considered precursor lesions of intestinal type gastric cancer. We have made a 1.5-yr follow-up study after H. pylori eradication, but no significant improvement of atrophy or IM has so far been found. Some other factors than H. pylori may also play an important part in the development and progress of atrophic gastritis. The discrepancy between our data and others may be caused in part by the different methods of assessment of the grade of atrophy and sampling of biopsies.

Follow-Up Studies↗

A new CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride in humans.

(+)-Cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) is a newly developed drug as a platelet-activating factor receptor antagonist. The disposition of SM-12502 was investigated in plasma from 28 healthy Japanese volunteers after a single i.v. administration of SM-12502. Three of 28 subjects were phenotyped as poor metabolizers (PMs). Genomic DNAs from three extensive metabolizers or three PMs of SM-12502 were analyzed by Southern blot analysis with CYP2A6 cDNA as a probe. DNAs from three PMs digested with SacI and SphI showed novel restriction fragment length polymorphisms (RFLPs); one type without 4.5- and 2.6-kb fragments and a weak density of a 6.4-kb fragment (E-type), and the other type without 7.1- and 5.5-kb restriction fragments (C'-type) as compared with three extensive metabolizers, respectively. The deletional restriction fragments specific to three PMs in SacI- and SphI-RFLPs were identified as CYP2A6. Using polymerase chain reaction-RFLP analyses of the gene from the three PMs, we found that the exon 1, exon 8, and exon 9 in CYP2A6 were absent. A new RFLP characterized by SacI and SphI was found to be due to the entire gene deletion of the three exons and was associated with the decreased metabolism of SM-12502. This study demonstrates a new deletional allele in the human CYP2A6 gene responsible for the poor metabolic phenotype of SM-12502.

Adult↗