A new method for synthesis of unsymmetrical ureas using electrochemically prepared trifluoroethyl carbamates.
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Amines↗
Biomedical subjects
Y Satoh
Publications and source records attributed to Y Satoh.
Potent and selective non-peptidic inhibitors of endothelin-converting enzyme-1 with sustained duration of action.
Potent and selective non-peptidic inhibitors of human endothelin-converting enzyme-1 (ECE-1) have been designed as potential modulators of endothelin (ET-1) production in vivo. Because of its unique structural characteristics and long duration of action in vivo, the dual ECE-1 and neutral endopeptidase 24.11 (NEP) inhibitor, CGS 26303, was selected as an attractive lead for further optimization of potency and selectivity. Replacement of the P(1)' biphenyl substituent of CGS 26303 by a conformationally restricted 3-dibenzofuranyl group led to more potent and more selective ECE-1 inhibitors, such as the tetrazole 27. The remarkable effect of this P(1)' modification allowed for the first time phosphonomethylcarboxylic acids, such as 29, to display both potent (IC(50) = 22 nM) and selective (104-fold vs NEP) ECE-1 inhibition. Chemoenzymatic syntheses of the new alpha-amino acid (S)-3-dibenzofuran-3-ylalanine intermediate were developed, and improved procedures to generate substituted alpha-aminoalkylphosphonic acids were devised to support the production of various analogues. Although additional gains in intrinsic ECE-1 inhibitory potency could occasionally be achieved by addition of a P(1) side chain, these compounds (e.g. 43a) showed poor functional activity in vivo in the big ET-1 pressor test. Phosphonoalkyl dipeptides featuring 3-dibenzofuranyl groups in both the P(1)' and P(2)' positions were also very potent ECE-1 inhibitors, albeit lacking the desired selectivity against NEP. Functionally, 27and 29 were the two most efficacious compounds from this study, producing sustained inhibition of ECE-1 activity in rats, as measured by their ability to block the hypertensive effects induced by big ET-1. This profile was similar to that of a potent ET(A)/ET(B) dual receptor antagonist, SB 209670. Due to their favorable in vitro and in vivo profiles, 27 (CGS 34043) and 29 (CGS 35066) constitute new pharmacological tools useful in assessing the role of ECE-1 in pathological conditions.
Animals↗
Aryl radical cyclizations of 1-(2'-bromobenzyl)isoquinolines with AIBN-Bu3SnH: formation of aporphines and indolo
[reaction: see text] Radical cyclization of alkoxy-substituted 1-(2'-bromobenzyl)-3,4-dihydroisoquinolines 1 with AIBN-Bu3SnH gave 6a,7-dehydroaporphines 2 preferentially. A steric repulsion between the respective alkoxy groups at the 7- and 3'-positions gave 5,6-dihydroindolo[2,1-a]isoquinolines 3 in a "disfavored" 5-endo cyclization mode. Radical cyclizations of the related substrates, such as 1-(2'-bromobenzoyl)isoquinolines or 1-(2'-bromo-alpha-hydroxybenzyl)isoquinolines, were also found to give the corresponding oxoaporphines or oxyaporphines.
Journal Article↗
Degeneration of the cerebellar dentate nucleus in corticobasal degeneration: neuropathological and morphometric investigations.
To resolve the controversy regarding the involvement of the dentate nucleus in corticobasal degeneration (CBD), an entire profile of the dentate nucleus was exposed in a sagittal plane and divided into four fields, and the number of neurons in each filed was counted separately using a computer-assisted analyzer in five cases of CBD and compared to those from seven age-matched controls. The size of the nucleus and the number of neurons were significantly reduced in all five cases of CBD. The neuronal loss had a definite regional predilection, more severe in the caudolateral neodentatum than in the rostromedial palaeodentatum, and was accompanied by grumose degeneration and astrogliosis which paralleled the severity of the neuronal loss. Thus, the dentate nucleus appears to be a cardinal target in CBD.
Aged↗
Intraductal ultrasonographic assessment of coagulation depth during endoscopic microwave coagulation therapy in a canine model.
In order to examine the feasibility of endoscopic microwave coagulation therapy (MCT) for the treatment of common bile duct cancer in humans, we investigated the safety and effectiveness of endoscopic MCT with the assistance of intraductal ultrasonography (IDUS). We performed MCT in the canine small intestine as a model because of its similarity in size to the obstructed human common bile duct. Multiple coagulation lesions were made in anesthetized dogs, with the endoscope inserted through a jejunostomy. Under condition "A", the tip of the MCT probe was kept in a fixed position in contact with the mucosa of the intestine, and coagulation was performed with an output of 30 or 50 W for 30 or 10 s, respectively. Under condition "B", the tip of the MCT probe was moved along the intestinal mucosa, and coagulation was performed with an output of 50, 40, or 30 W, all for 10 s. After coagulation, a thin-caliber ultrasonic probe was inserted endoscopically for observation of the effects of coagulation. Each coagulation under condition "A" resulted in degeneration of all layers of the intestine. Coagulation under condition "B" resulted in more localized degeneration, extending from the mucosal layer to the proper muscle layer. By comparison with histologic observations, the accuracy of IDUS in assessing depth of degeneration was 87.5%. Endoscopic microwave coagulation was considered safe and effective, and IDUS was able to accurately assess the effects of microwave coagulation.
Animals↗
Limitations of three-dimensional intraductal ultrasonography in the assessment of longitudinal spread of extrahepatic bile duct carcinoma.
We investigated the utility and limitations of three-dimensional intraductal ultrasonography (3D-IDUS), for the assessment of the extent of longitudinal cancer spread to the hepatic side by extrahepatic bile duct carcinoma. In eight patients with extrahepatic bile duct carcinoma. 3D-IDUS was used to assess longitudinal cancer extension to the hepatic side prior to resection. When the linear dimension of 3D-IDUS showed bile duct wall thickening that was connected to the tumor and which became thin at a point, it was determined to be the front formation of longitudinal cancer extension. The findings were examined in relation to histologic information from the resected specimen. Although 3D-IDUS showed front formation of wall thickening in two patients, it accurately reflected the histological margin of the longitudinal cancer extension in only one patient. In the other patient, the wall thickening was longer than the histological margin. When 3D-IDUS showed bile duct wall thickening without front formation (n = 2), the wall thickening was longer than the histological margin of the longitudinal cancer extension. Even when 3D-IDUS did not show wall thickening (n = 4), one of these patients showed cancer spread histologically. As a result, the accuracy in assessing longitudinal cancer extension by 3D-IDUS was only 50%. Even if the linear dimension of 3D-IDUS demonstrated front formation of thickening of the bile duct, it reflected not only cancer extension but also inflammatory wall thickening.
Aged↗
Percutaneous recanalization of the bile duct along an endoscopic naso-biliary catheter.
Percutaneous recanalization of the bile duct is essential for placing biliary stents and carrying out other interventions. This prospective study was performed to establish safe approaches for percutaneous recanalization of the bile duct when it had previously resulted in failure. Between July 1995 and July 1999, percutaneous recanalization of the bile duct was attempted in 58 patients with a malignant biliary stenosis. When recanalization failed, an endoscopic naso-biliary drainage (ENBD) catheter was placed across the stenosis. The procedure was again attempted along the ENBD catheter. In the period of the study, four patients underwent successful recanalization after ENBD, although attempts prior to ENBD had been unsuccessful. As a result, the success rate of recanalization in the period was 100% (58/58). When recanalization fails, the use of an ENBD catheter may provide access to the biliary tree, and the biliary stenosis can be recanalized safely.
Abdominal Neoplasms↗
Placement of endoscopic naso-biliary drainage does not preclude subsequent percutaneous transhepatic biliary drainage.
We prospectively investigated whether the placement of endoscopic naso-biliary drainage (ENBD) precluded percutaneous transhepatic biliary drainage (PTBD). In 40 patients, the caliber of the intrahepatic bile duct was measured prior to ENBD by ultrasonography. When PTBD was required after ENBD, the ENBD catheter was clamped for 1 to 2 h before PTBD, and its caliber was again measured at the time of PTBD. When PTBD was performed within 7 days (mean, 1.8 days) after ENBD (n = 27), the size of the intrahepatic bile duct was 5.0 +/- 2.3 mm before and 4.6 +/- 2.3 mm after ENBD. There was no significant difference between these values (P > 0.5). When PTBD was performed 8 to 40 days (mean, 17.8 days) after ENBD (n = 13), the bile duct diameter was significantly reduced, from 4.2 +/- 1.5 mm (pre-ENBD) to 1.8 +/- 1.7 mm (post-ENBD) (P < 0.05). When PTBD was conducted within 7 days (mean, 1.8 days) after ENBD, previous ENBD did not induce collapse of the bile duct, if the ENBD catheter was clamped for 1 to 2 h before the puncture of the bile duct.
Bile Ducts, Intrahepatic↗
Intraductal US in assessing the effects of radiation therapy and prediction of patency of metallic stents in extrahepatic bile duct carcinoma.
BACKGROUND: We assessed the local effects of radiation therapy using intraductal ultrasonography (US) to predict the subsequent patency of metallic stents in bile duct carcinoma. METHODS: Data from 16 patients with extrahepatic-suprapancreatic bile duct carcinoma were prospectively analyzed. Thin-caliber US probes (2.0 mm diameter/20 MHz frequency and 2.8 mm diameter/10 MHz frequency) were inserted into the bile duct via a percutaneous transhepatic approach pre- and postradiation therapy to evaluate the effects of treatment. When intraductal US showed a reduction in bile duct wall thickness of 30% or greater or showed a lessening of vessel (portal vein or right hepatic artery) invasion, radiation therapy was judged to be effective. Noncovered metallic stents were then inserted, and their patency was evaluated over time. RESULTS: When radiation therapy was effective (n = 7), the metallic stent was patent for 522 +/- 571 days. When radiation was ineffective (n = 9), the metallic stent was patent for only 188 +/- 159 days. When radiation therapy was ineffective, stent obstruction occurred in 6 of 9 (66.7%) patients during this period, significantly more frequently than when radiation therapy was effective (14.3%, p < 0.05). CONCLUSIONS: Assessment of local radiation effects by intraductal US is useful for predicting patency of metallic stents in bile duct cancer.
Aged↗
A comparison and conversion table of 'the House-Brackmann facial nerve grading system' and 'the Yanagihara grading system'.
A comparison between the House-Brackmann facial nerve grading system (the HB-system) and the Yanagihara grading system (the Y-system) was studied with 199 evaluations of 62 cases of postoperative unilateral acoustic neuroma. In the beginning, an original draft of the conversion table was formulated according to the 199 evaluations, in which, 0-6, 8-14, 16-20, 22-28, 30-38, and 40 points in the Y-system were matched with grade VI, V, IV, III, II, and I in the HB-system respectively. The result of the present study for prediction of sequelae showed that it was not necessary to consider the sequelae in a conversion table. And more, the study of an inter-observer variation showed that the lower and upper limits of the scores in the Y-system may shift within about a 2-point range in the draft table. From these aspects, a newly revised conversion table was proposed as a revised conversion table, in which, 0-6, 8-14, 16-22, 24-30, 32-38, and 40 points in the Y-system were matched with grade VI, V, IV, III, II, and I in the HB-system. This revised conversion table is much easier to remember for clinical use, because the score of the lower limit of each grade is simply in multiples of 8, that is, 0, 8, 16, 24, 32 and 40.
Facial Nerve↗
Detection of Epstein-Barr virus in salivas and throat washings in healthy adults and children.
It is well known that Epstein-Barr virus (EBV) is excreted from oral regions in the patients with infectious mononucleosis. We analyzed the prevalence of EBV in saliva and throat washings from healthy people in Japan by the polymerase chain reaction assay. EBV DNA was detected in 43 (90%) of the 48 throat washings from healthy adults (21 to 57 years old) and in 35 (38%) of the 93 salivas from healthy children (0 to 6 years old). The percentages of the EBV DNA-positive ratio in salivas increased in proportion relative to the increase of the children's ages. EBV type 1 was predominant and was detected in 86 and 94% of adults and children, respectively. Umbilical cord lymphocytes were transformed by some throat washings from EBV seropositive donors. EBV DNA was detected in throat washings from two healthy adults whose EBV antibody was not detected. In both cases, higher amounts of EBV DNA were detected in their peripheral blood mononuclear cells than in those of other, EBV antibody-positive donors. These results demonstrated the incidence of EBV excretion in oral regions of healthy individuals in Japan and defined a novel type of EBV infection in healthy adults.
Adult↗
Differential effect of TPA on cell growth and Epstein-Barr virus reactivation in epithelial cell lines derived from gastric tissues and B cell line Raji.
We characterized the cell growth and Epstein-Barr virus (EBV) reactivation for EBV infected epithelial cell lines, GT38, GT39, and GTC-4 using 12-O-tetradecanoylphorbol-13-acetate (TPA). These cell lines grew similarly in liquid medium, and formed colonies in soft agar. The cell growth was inhibited with TPA, dose-dependently in liquid medium. The colony formation was enhanced with low concentrations of TPA, but was inhibited with high concentrations. The latent EBV was reactivated with high concentrations of TPA as shown by the expression of EBV BZLF1 gene product ZEBRA. The effects of TPA on GTC-4 were compared with a Burkitt's lymphoma cell line Raji. The mode of actions of TPA in GTC-4 was different from Raji in terms of cell growth and EBV reactivation. The effective concentrations of TPA for cell growth inhibition and EBV reactivation were higher in Raji than GTC-4. Cell cycle analysis showed that TPA (20 ng/ml) induced cell cycle arrest to Raji but not to GTC-4; however, the rate of trypan blue stained cells increased in the TPA treated GTC-4 but not Raji. These results demonstrated that TPA affects differentially for the stimulation and inhibition of cell growth, and also EBV reactivation depends on TPA concentrations and cell types.
Blotting, Western↗
Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5.
The mature form of Alzheimer's beta-amyloid precursor protein (APP) is phosphorylated specifically at Thr(668) in neurons. In mature neurons, phosphorylated APP is detected in neurites, with dephosphorylated APP being found mostly in the cell body. In vitro, active cyclin-dependent kinase 5 (Cdk5) phosphorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature neurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and significantly diminished the level of phosphorylated APP. The expression of APP was unaffected in antisense-treated neurons. These results indicate that in neurons APP is phosphorylated by Cdk5, and that this may play a role in its localization.
Amyloid beta-Protein Precursor↗
Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder.
A high association between type 2 diabetes mellitus and depressive illness has been reported. Insulin resistance during depressive illness might contribute to the linkage between depression and type 2 diabetes. To determine whether the genetic polymorphisms of the tyrosine hydroxylase ([TH] HUMTH01) and insulin (INS-VNTR) genes contribute to insulin resistance in depressive illness, we analyzed the association between the polymorphisms and insulin resistance in 41 Japanese patients with depressive disorder, 204 normal control subjects, 161 cohort subjects with normal glucose tolerance (NGT) and without depressive symptomatology, and 59 NGT subjects with depressive symptomatology. The depressive patients had a significantly lower insulin sensitivity index (SI) than the control subjects (P= .016). Depressive NGT subjects had a significantly higher homeostasis model assessment (HOMA) insulin resistance index [HOMA(R)] than the nondepressive NGT subjects (P < .0001). The depressive patients and NGT subjects had more HUMTH01 allele 7 (TH7) than the controls and nondepressive NGT subjects. SI was significantly lower in patients with the TH7/7 homozygote versus patients with the other genotypes and the controls. TH7 was associated with higher HOMA(R) as compared with the other alleles in the NGT subjects. Insulin resistance was associated with depressive disorders. The HUMTH01 and INS-VNTR were associated with insulin resistance and depressive symptoms.
Adult↗
Double-catheter method to prevent dislodgement during percutaneous transhepatic cholangioscopy.
BACKGROUND: We evaluated the utility of the double-catheter method to establish the track for percutaneous transhepatic cholangioscopy (PTCS). METHODS: Dilatation of the percutaneous transhepatic track to 16F for PTCS was attempted in 105 patients. The results were prospectively analyzed. Using the single-catheter method (n = 22), a 16F PTCS catheter was replaced without the inner catheter. Using the double-catheter method (n = 83), a 7F catheter with a balloon tip was inserted through a 16F PTCS catheter. The balloon was located distal to the major duodenal papilla. The double-catheter method was further subclassified as follows: Method 2A (n = 62), the tip of the outer catheter (16F) was not advanced through biliary stenoses; Method 2B (n = 21), the catheter was advanced through biliary stenoses. RESULTS: In the patients treated by the double-catheter method, dislodgement of the catheter did not occur, whereas the single-catheter became dislodged in 18% (p < 0.0005). The morbidity of method 2A (0%) was less than that of method 2B (14%) (p < 0.005). CONCLUSION: The double-catheter method prevents dislodgement of the PTCS catheter. The outer catheter should not be advanced to the biliary stenosis.
Adult↗
Access for percutaneous transhepatic cholangioscopy in patients with nondilated bile ducts using nasobiliary catheter cholangiography and oblique fluoroscopy.
BACKGROUND: Percutaneous transhepatic biliary drainage is required for percutaneous transhepatic cholangioscopy. However, puncture of nondilated bile ducts under ultrasonographic guidance is difficult. METHODS: In 10 patients with no ultrasonographic evidence of intrahepatic bile duct dilatation, percutaneous transhepatic biliary drainage was performed under fluoroscopic guidance using cholangiography obtained via a nasobiliary drainage catheter. Direct puncture was performed by means of a left ventral approach using oblique C-arm fluoroscopy. RESULTS: Bile duct puncture was successful in all patients. There were no procedure-related complications. Subsequent cholangioscopy was successful in all patients. CONCLUSIONS: Direct puncture using nasobiliary drainage cholangiography and oblique fluoroscopy is a useful method when cholangioscopy is necessary in patients with nondilated bile ducts.
Adult↗
Cardiovascular responses to epinephrine-containing local anesthetics for dental use: a comparison of hemodynamic responses to infiltration anesthesia and ergometer-stress testing.
OBJECTIVE: Cardiovascular effects of infiltration anesthesia have been documented in numerous studies. However, few studies have been carried out to compare the effects of infiltration anesthesia with the effects of exercise-stress testing. The purpose of this study was to examine this issue. STUDY DESIGN: Eight young and 13 older subjects were given infusions of epinephrine to produce cardiovascular responses comparable with those found in subjects undergoing infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E). Cardiovascular responses to this drug treatment were evaluated with echocardiography and compared with those produced by ergometer exercise. RESULTS: The hemodynamic effects of L-E infiltration anesthesia were less than those produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15 W in the older subjects. The workload of this ergometer-stress testing was about 4 metabolic equivalents (METS), which is approximately equivalent to the workload of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or pushing a power mower), painting, or doing light carpentry. CONCLUSION: With the exception of some specific pathologic conditions, such as serious arrhythmia, infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the patients who have exercise capacity of more than 4 METS.
Adult↗
A novel imprinted gene, KCNQ1DN, within the WT2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms' tumors.
WT2 is defined by a maternal-specific loss of heterozygosity on human chromosome 11p15.5 in Wilms' and other embryonal tumors. Therefore, the imprinted genes in this region are candidates for involvement in Wilms' tumorigenesis. We now report a novel imprinted gene, KCNQ1DN (KCNQ1 downstream neighbor). This gene is located between p57(KIP2) and KvLQT1 (KCNQ1) of 11p15.5 within the WT2 critical region. KCNQ1DN is imprinted and expressed from the maternal allele. We examined the expression of KCNQ1DN in Wilms' tumors. Seven of eighteen (39%) samples showed no expression. In contrast, other maternal imprinted genes in this region, including p57(KIP2), IMPT1, and IPL exhibited almost normal expression in these samples, although some samples expressed IGF2 biallelically. These results suggest that KCNQ1DN existing far from the H19/IGF2 region may play some role in Wilms' tumorigenesis along with IGF2.
Chromosome Mapping↗