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Biomedical subjects

N Ueda

Publications and source records attributed to N Ueda.

At least 73 records · Page 4Linked to original sources
PubMed2000

The fatty acid amide hydrolase (FAAH).

The topic of this review is fatty acid amide hydrolase (FAAH), one of the best-characterized enzymes involved in the hydrolysis of bioactive lipids such as anandamide, 2-arachidonoylglycerol (2-AG), and oleamide. Herein, we discuss the nomenclature, the various assays that have been developed, the relative activity of the various substrates and the reversibility of the enzyme reactions catalyzed by FAAH. We also describe the cloning of the enzyme from rat and subsequent cDNA isolation from mouse, human, and pig. The proteins and the mRNAs from different species are compared. Cloning the enzyme permitted the purification and characterization of recombinant FAAH. The conserved regions of FAAH are described in terms of sequence and function, including the amidase domain which contains the serine catalytic nucleophile, the hydrophobic domain important for self association, and the proline rich domain region, which may be important for subcellular localization. The distribution of FAAH in the major organs of the body is described as well as regional distribution in the brain and its correlation with cannabinoid receptors. Since FAAH is recognized as a drug target, a large number of inhibitors have been synthesized and tested since 1994 and these are reviewed in terms of reversibility, potency, and specificity for FAAH and cannabinoid receptors.

Amidohydrolases↗
PubMed2000

Anandamide amidohydrolase (fatty acid amide hydrolase).

Anandamide (N-arachidonoylethanolamine) loses its cannabimimetic activity when it is hydrolyzed to arachidonic acid and ethanolamine by the catalysis of an enzyme referred to as anandamide amidohydrolase or fatty acid amide hydrolase. Cravatt's group and our group cloned cDNA of the enzyme from rat, human, mouse and pig, and the primary structures revealed that the enzymes belong to an amidase family characterized by the amidase signature sequence. The recombinant enzyme acted not only as an amidase for anandamide and oleamide, but also as an esterase for 2-arachidonoylglycerol. The reversibility of the enzymatic anandamide hydrolysis and synthesis was also confirmed with a purified recombinant enzyme. Several fatty acid derivatives like methyl arachidonyl fluorophosphonate potently inhibited the enzyme. The enzyme was distributed widely in mammalian organs such as liver, small intestine and brain. However, the anandamide hydrolyzing enzyme found in human megakaryoblastic cells was catalytically distinct from the previously known enzyme.

Amidohydrolases↗
PubMed2000

Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations.

The aim of this paper is to describe two cases of clomipramine-induced delirium. One 61-year-old and one 67-year-old female depressive patients became delirious after beginning intravenous clomipramine injections in addition to their oral clomipramine administrations. Their plasma levels of both clomipramine and its metabolite, desmethylclomipramine, were acutely increased about twofold during delirium. The intravenous clomipramine administrations were discontinued. Their delirious state was gradually improved after stopping the intravenous clomipramine administrations. These findings suggest that acute increases of plasma levels of clomipramine and desmethylclomipramine after intravenous clomipramine injections might be related to the appearance of the delirious episodes.

Aged↗
PubMed2000

Gene transfer targeting interstitial fibroblasts by the artificial viral envelope-type hemagglutinating virus of Japan liposome method.

BACKGROUND: Tubulointerstitial inflammation and fibrosis are commonly associated with most human glomerular diseases. The degree of tubulointerstitial damage, rather than the glomerular injury, could correlate with the degree of renal functional impairment and accurately predict long-term prognosis. In an effort to understand the pathogenesis of the progressive interstitial fibrosis, we developed a new strategy of gene transfer to the interstitial fibroblasts. METHODS: Either fluorescein isothiocyanate (FITC)-labeled oligodeoxynucleotides (ODNs) or pEBAct-NlacF expression vector was introduced into the kidney of normal rats retrogradely via ureter by using the artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome method. RESULTS: FITC-labeled ODNs were accumulated diffusely in the nuclei of the interstitial cells in the transfected kidney 10 minutes after transfection, and the interstitial cells were identified as interstitial fibroblasts by immunostaining with ER-TR7. To examine the gene expression in the interstitium, pEBAct-NlacF gene-conjugated HVJ liposome was injected retrogradely through the ureter, and in consequence, nuclear beta-galactosidase activity was continuously observed in interstitial cells at least two weeks after transfection. CONCLUSION: This new strategy of gene transfer to the interstitial fibroblasts is useful for the investigation of the pathophysiology of tubulointerstitial lesion, and furthermore, it may be a promising new therapeutic method for the progression of interstitial fibrosis.

Animals↗
PubMed2000

Kinesin is involved in regulation of rat pancreatic amylase secretion.

BACKGROUND & AIMS: Kinesin has recently been localized to zymogen granules of pancreatic acini and is suggested to participate in exocytosis of exocrine pancreas. We examined the function of kinesin in regulated exocytosis of pancreatic acini in this study. METHODS: Kinesin function in exocytosis was examined by introducing hexahistidine-tagged recombinant kinesin protein and antikinesin monoclonal antibody into streptolysin-O-permeabilized acini. Intracellular localization of introduced recombinant kinesin was investigated by immunohistochemistry. Interaction between recombinant kinesin and the microtubule network was confirmed by nocodazole pretreatment of acini. Kinesin regulation by secretagogues was investigated by examining their effect on adenosine triphosphatase (ATPase) activity of endogenous kinesin. RESULTS: Recombinant kinesin enhanced calcium-stimulated amylase release from streptolysin-O-permeabilized acini. Introduced recombinant kinesin was localized to both the microtubule network and zymogen granule. Nocodazole pretreatment of acini abolished the enhancing effect of recombinant kinesin on calcium-stimulated amylase release. Antikinesin antibody inhibited amylase release stimulated by the combination of calcium and cyclic adenosine monophosphate (cAMP) but not that stimulated by calcium alone. Secretin and 8-bromo-cAMP increased ATPase activity of endogenous kinesin. CONCLUSIONS: Kinesin plays a stimulatory role in regulated exocytosis of pancreatic acini and is involved in stimulus-secretion coupling through a cAMP-dependent pathway.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2000

Morphology and dynamics of the ulnar nerve in the cubital tunnel. Observation by ultrasonography.

We examined 200 normal elbows to assess the usefulness of ultrasonography in examining the ulnar nerve in the cubital tunnel. On longitudinal images in elbow extension, the nerve changed its course at the fibrous band region 11.5 (SD 2.8) mm distal to the medial epicondyle. On axial images, the diameter of the major axis of the nerve was 3.1 (0.5) mm and that of the minor axis was 1.9 (0.4) mm in men. The respective values were 2.7 (0.4) mm and 1.8 (0.4) mm in women. Dynamic studies showed that in 53 elbows (27%), the nerve moved on to the tip of the epicondyle with the elbow flexed and in 39 elbows (20%), the nerve dislocated anteriorly. The diameters of the hypermobile nerves were significantly larger than nerves that did not displace.

Adult↗
PubMed2000

Diagnostic ultrasonography of the ulnar nerve in cubital tunnel syndrome.

Thirty-two elbows in 31 patients diagnosed as having cubital tunnel syndrome underwent ultrasonographic examination to assess morphological changes in the ulnar nerve and its surrounding tissues. On longitudinal images, the site of constriction due to the fibrous band and proximal swelling of the nerve were observed by ultrasonography and were confirmed intraoperatively. On axial images, the lengths of the major axis [7.2 (SD 1.6) mm] and the minor axis [3.7 (0.9) mm] of the nerve at the medial epicondyle were greater than those in normal subjects. There was a correlation between the stage of ulnar nerve palsy and the diameter of the major axis. Preoperatively, ganglia were detected by ultrasonography in the cubital tunnel in three cases and an anconeus epitrochlearis muscle in two.

Cubital Tunnel Syndrome↗
PubMed2000

In vivo and in vitro study of radio-frequency application with a new long linear probe: implication for the maze operation.

BACKGROUND: The maze operation for atrial fibrillation is effective but highly invasive. We tested, both in vitro and in vivo, a new technique for creating long linear atrial lesions with a custom-made, 25-mm long, stainless-steel, linear probe and a corresponding 500-kHz generator for assistance in the maze operation. METHODS: In the in vitro study with the isolated canine atria, the power of the delivered radio-frequency energy and the saline irrigating flow rate were changed independently, and the sizes of the lesions were measured. In the in vivo study radio-frequency energy was delivered to 4 portions (ie, the smooth and trabeculated portions of the right and left atria). The sizes of the lesions were measured, and the histologic features of the lesions were examined. Electrical isolation of the right atrial appendage from the remaining right atrium was attempted by using this linear probe. RESULTS: In the in vitro study the size of the lesion became larger as the delivered power was increased, although the lesion was limited when the flow rate was high. In the in vivo study the size of the lesion was equal at the 4 different sites. Histologic examinations demonstrated linear and transmural lesions, and electrophysiologic examinations revealed conduction block between the right atrial appendage and the remaining right atrium. CONCLUSIONS: The new original long linear probe was effective for creating transmural linear atrial lesions with the irrigation method, presenting the possibility of an intraoperative technique that mimics the maze procedure.

Animals↗
PubMed2000

Effect of risperidone on plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels in schizophrenic patients: relationship among plasma concentrations of risperidone and 9-hydroxyrisperidone, pMHPG levels, and clinical improvement.

We examined the relationships among the clinical efficacies of risperidone, plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone, and changes in plasma free MHPG (pMHPG) in 14 schizophrenic patients. Clinical improvement in negative symptoms of schizophrenia treated with risperidone has been associated with increased pMHPG and, in the present study, there were positive correlations between plasma 9-hydroxyrisperidone concentrations and increased pMHPG levels. These results suggest that risperidone might improve negative symptoms in schizophrenia by influencing noradrenergic neurons.

Adolescent↗
PubMed2000

Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine.

The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and found that the low dosage of levomepromazine was effective in counteracting the fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels. These results suggest that the inhibition of CYP2D6 by levomepromazine has little effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine, used as a hypnotic agent, appears to be effective and safe when coadministered with fluvoxamine. Since this was a pilot study without a placebo control, a double-blind placebo-controlled study is needed to confirm our preliminary findings.

Adult↗
PubMed2000

Radiofrequency catheter ablation of upper septal idiopathic left ventricular tachycardia exhibiting left bundle branch block morphology.

Idiopathic left ventricular (LV) tachycardia usually exhibits right bundle branch block morphology. There are only a few sporadic cases that exhibit left bundle branch block (LBBB) morphology. We report a patient whose QRS complex during ventricular tachycardia (VT) was relatively narrow (100 msec) and exhibited LBBB (precordial R wave transition between V3 and V4) and a normal frontal plane axis. This VT was ablated successfully by radiofrequency current applied to the LV upper septum, where the earliest endocardial activation was recorded.

Adolescent↗
PubMed2000

SMEM algorithm for mixture models.

We present a split-and-merge expectation-maximization (SMEM) algorithm to overcome the local maxima problem in parameter estimation of finite mixture models. In the case of mixture models, local maxima often involve having too many components of a mixture model in one part of the space and too few in another, widely separated part of the space. To escape from such configurations, we repeatedly perform simultaneous split-and-merge operations using a new criterion for efficiently selecting the split-and-merge candidates. We apply the proposed algorithm to the training of gaussian mixtures and mixtures of factor analyzers using synthetic and real data and show the effectiveness of using the split-and-merge operations to improve the likelihood of both the training data and of held-out test data. We also show the practical usefulness of the proposed algorithm by applying it to image compression and pattern recognition problems.

Algorithms↗
PubMed2000

In vitro absorption and metabolism of a citrus chemopreventive agent, auraptene, and its modifying effects on xenobiotic enzyme activities in mouse livers.

We previously reported that auraptene (7-geranyloxycoumarin, AUR), widely occurring in citrus fruit, is a structurally novel type of effective cancer-preventive agent, as manifested in several rodent models. However, its bio-availability and metabolism in biological systems have yet to be investigated. In the present study, we examined the chemical stability of AUR at pH 1.57 and 37 degrees C (as a stomach digestion model) and observed its stoichiometric conversion to umbelliferone [7-hydroxycoumarin, UMB; half-life (t1/2) = 15 h; 7-ethoxycoumarin (ETC) was stable for 24 h]. Differentiated Caco-2 cells, a human colorectal adenocarcinoma cell line, were used as a small intestine model. ETC permeated the basolateral (portal vein) side of Caco-2 cells in a time-dependent manner; AUR slightly permeated the cells, but with an intracellular accumulation. Epoxyauraptene and UMB were detected when AUR was treated with the rat liver S-9 mixture. ETC was also converted to UMB, but its t1/2 of two hours was much shorter than that of AUR (> 24 h). This suggests that AUR, bearing a geranyloxyl side chain, is a relatively metabolism-resistant substrate for cytochrome P-450 enzymes and, thus, is stable in the liver compared with ETC. Oral administration of AUR by gavage at 50-200 mg/kg body wt dose dependently induced glutathione S-transferase (GST) activity in mouse livers without affecting cytochrome P-450 activity. Using 10 coumarin-related compounds, we found that only those coumarins having a 7-alkyloxyl group induced GST, but not cytochrome P-450, activity. The present study presumes that AUR accumulates in the epithelial cells of the small intestine and then gradually permeates into the portal vein. Stable localizability of AUR in the colon and liver may be associated with the induction of GST activity, which is important as the action mechanism for suppression of rodent chemical carcinogenesis.

Absorption↗
PubMed2000

Influence of right atrial structure on outcome of radio-frequency catheter ablation for common atrial flutter.

Radiofrequency catheter ablation (RFCA) targeting the cavotricuspid isthmus is usually an effective treatment for common atrial flutter (AFL), except in a small subset of patients and the reason for this has yet to be elucidated. The present study investigated the relationship between the outcome of RFCA for common AFL and the anatomy of the right atrium as seen on angiography. Twenty consecutive patients who underwent RFCA for common AFL were divided into 2 groups according to the results of RFCA. Group A comprised 13 patients whose AFL was abolished, fulfilling the criteria of success by the conventional catheter approach, and group B comprised 7 patients whose AFL could not be abolished according to the criteria for success (n=4) or was abolished following an additional superior vena cava approach (n=3). On angiography, the cavotricuspid isthmus was longer (3.5+/-0.5 vs 2.2+/-0.6 cm) and deeper (0.94+/-0.35 vs 0.49+/-0.19 cm) in group B than in group A (both p<0.01). The height of the eustachian valve was also greater in group B than in group A (1.4+/-1.1 vs 0.48+/-0.48 cm, p<0.02). These results suggest that the anatomical structure of the cavotricuspid isthmus affects the outcome of RFCA for common AFL.

Adolescent↗
PubMed2000

Effects of pH variation and NaCl on in vitro digestibility of cow's milk proteins in commercially available infant formulas.

Allergenicity and antigenicity of food proteins are generally dependent on their heat-stability and resistance to digestive enzymes. Using the methods of SDS-PAGE and immunoblots, we assessed peptic-digestibility of major milk proteins (casein, beta-lactoglobulin and alpha-lactalbumin) in commercially available infant formulas in acidic pH range (pH 1.5 to 4.0), and we also investigated the effect of NaCl on peptic-digestibility of cow's milk proteins at pH 2.0. The profile of peptic-digestion of casein was similar at pH range from 1.5 to 3.5 where the intact protein of casein rapidly disappeared, whereas slow digestibility of the protein was found at pH 4.0. Beta-lactoglobulin and alpha-lactalbumin were digested at pH range from 1.5 to 2.5 and were almost entirely resistant to peptic digestion at over pH 3.0. In the presence of NaCl at pH 2.0, casein showed a good digestibility by pepsin similar to that in the absence of NaCl, in contrast to beta-lactoglobulin and alpha-lactalbumin both having their peptic-digestibility decreased in the presence of 0.2 M NaCl. As the state of the stomach in new born infants shows low amounts of secretary pepsin and out of optimum pH of peptic activity, low digestibility of beta-lactoglobulin and alpha-lactalbumin in cow's milk based infant formulas at over pH 3.0 is supposed to be responsible for their allergenicity.

Animals↗
PubMed2000

Clinical usefulness of telomerase assay for the detection of lymph node metastasis in patients with oral malignancy.

OBJECTIVE: Telomerase is considered a diagnostic marker of malignancy. We investigated the usefulness of telomerase assay for the detection of lymph node micrometastasis. METHODS: Sixteen cervical lymph nodes with metastasis of oral cancer and 20 benign lymph nodes were studied. The oral cancer cell line was used to estimate the sensitivity for telomerase assay. Telomerase activity was measured by semiquantitative telomeric repeat amplification protocol. RESULTS: There was a significant difference between malignant and benign lymph nodes. The telomerase activity of 50 mg of lymph nodes with 103 or more cancer cells differed from that of control lymph nodes. Lymph nodes with 102 or fewer tumor cells expressed similar levels as benign lymph nodes. CONCLUSIONS: In addition to routine histologic examination, telomerase assay is considered a useful tool for the detection of lymph node metastasis in patients with oral malignancy.

Biomarkers, Tumor↗