[Anandamide and its related compounds].
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Animals↗
Biomedical subjects
N Ueda
Publications and source records attributed to N Ueda.
[A case of hepatic arterial infusion chemotherapy with docetaxel for liver metastasis from breast cancer].
We experienced a case of hepatic arterial infusion chemotherapy using docetaxel for liver metastasis, which showed no response to CEF therapy, from breast cancer. A 63-year-old woman had undergone modified radical mastectomy for right breast cancer (T2aN1bM0: Stage II) in October, 1995. Six-cycle CMF therapy and toremifene citrate (40 mg/day) were administered as adjuvant therapy, but multiple recurrent tumors in liver, lung, and local site were detected in February 1997. Six-cycle CEF therapy was given for recurrent disease and there was a complete response for lung and local recurrence, but no change in liver metastasis. Chemoendocrine therapies using 5'-DFUR or CMitF in addition to TAM and fadrozole hydrochloride hydrate had developed progressive disease for liver metastasis. A catheter and port kit were operatively inserted and implanted in March 1998. Hepatic arterial infusion of docetaxel (30-40 mg/body/month, one hour administration) was repeated 4 times, once in our clinic. Leukopenia, general fatigue and fever, which were mild and did not require any treatment, appeared as side effects. This treatment reduced multiple liver metastatic sites on abdominal CT finding and was thought to be a partial response. However, the patient had multiple brain metastasis and died on August 2, 1998. While docetaxel, even by systemic administration, has a 36-77% response rate for liver metastasis, arterial infusion might have a good response and mild side effect with a lower dose than by intravenous administration.
Antineoplastic Agents, Phytogenic↗
[Missense mutations of the butyrylcholinesterase gene in six Japanese patients with low cholinesterasemia: genetic analysis using sera stored in a freezer].
Six serum samples with no detectable butyrylcholinesterase (BCHE) activity had been stored at -70 degrees C for more than 10 years. These sera were used for amplification of BCHE gene using polymerase chain reaction (PCR) and for nucleotide sequence analysis. Five of them demonstrated a C-->T transition at codon 100 (CCA-->TCA), resulting in a Pro-->Ser substitution. The other one was a compound heterozygote as revealed a T-->C transition mutation at codon 203 from TCA (Ser) to CCA (Pro) and G-->C transversion at codon 365 from GGA (Gly) to CGA (Arg). These results showed sera stored in a freezer could be used as a starting material for amplification of genomic DNA when it is not possible to obtain fresh blood samples.
Asian People↗
Multimedia unplugged: a workshop on learning designs at the neoMuseum, Japan.
In Japan, we have a growing field called 'Information Education,' but people are paying too much attention to computers and the internet. That's why I am proposing unplugging the computer and thinking about the more essential aspects of learning and information design. 'Unplugged' means that technology and multimedia need not be limited to digital forms. Pencil-and-paper and traditional 'by hand' media also have important roles to play. In the Multimedia Unplugged workshop, participants use different forms of expression and media, including paper and styrofoam cubes, freeform construction kits and a wide variety of everyday objects, like bamboo leaves and post-it papers. Through this workshop, participants can understand that each medium has its own constraints and opportunities, and have a change to rethink the roles of multimedia from new perspectives. They can then replug and thus be able to choose appropriate media--digital or physical or both--to express their ideas.
Art↗
Anxiolytic 5-hydroxytryptamine1A agonists suppress firing activity of dorsal hippocampus CA1 pyramidal neurons through a postsynaptic mechanism: single-unit study in unanesthetized, unrestrained rats.
Recent behavioral studies indicate that conditioned fear response to contextual stimuli is reduced effectively by anxiolytic 5-hydroxytryptame (5-HT)1A agonists. Since the hippocampus seems to play an essential role in associative fear memories evoked by context, it is important to assess the effect of 5-HT1A agonists on pyramidal cell activity in the hippocampus. We examined the effects of 5-HT1A agonists on the spontaneous firing rate of hippocampal CA1 pyramidal neurons in unanesthetized, unrestrained rats. Systemic administration of selective 5-HT1A agonists, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, ipsapirone, and flesinoxan produced a dose-dependent inhibition of neuronal activity. Putative 5-HT1A antagonists NAN-190 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine and (-)-pindolol did not change neuronal activity of CA1 pyramidal neurons. The suppression of neuronal activity by buspirone was antagonized by NAN-190 but not by (-)-pindolol. Lack of antagonistic activity of (-)-pindolol for the suppression of pyramidal neurons via a postsynaptic mechanism is consistent with the results of recent electrophysiological experiments in anesthetized rats. Pretreatment with parachlorphenylalanine did not change the spontaneous firing rates of hippocampal CA1 pyramidal neurons or abolish the suppressant effects of buspirone on these neurons. Taken together, the present results strongly suggest that suppression of the hippocampal CA1 pyramidal neuronal activity by anxiolytic 5-HT1A agonists in awake rats is mediated by postsynaptic 5-HT1A receptors located on pyramidal neurons.
Animals↗
Biosynthesis and degradation of bioactive fatty acid amides in human breast cancer and rat pheochromocytoma cells--implications for cell proliferation and differentiation.
The endogenous cannabinoid, anandamide (arachidonoylethanolamide), and the sleep-inducing factor, oleamide (cis-9-octadecenoamide), represent two classes of long-chain fatty acid amides with several neuronal actions and metabolic pathways in common. Here we report that these two compounds are present in human breast carcinoma EFM-19 cells and rat adrenal pheochromocytoma PC-12 cells, together with the enzyme responsible for their degradation, fatty acid amide hydrolase, and the proposed biosynthetic precursors for arachidonoylethanolamide and related acylethanolamides, the N-acyl-phosphatidylethanolamines. Lipids extracted from cells labelled with [14C]ethanolamine contained radioactive compounds with the same chromatographic behaviour as arachidonoylethanolamide and acyl-PtdEtns. The levels of these compounds were not influenced by either stimulation with ionomycin in EFM-19 cells or two-week treatment with the nerve growth factor in PC-12 cells. The chemical nature of arachidonoylethanolamide, related acylethanolamides and the corresponding acyl-PtdEtns was confirmed by gas chromatographic/mass spectrometric analyses of the purified compounds, which also showed the presence of higher levels of oleamide. The latter compound, which does not activate the central CB1 cannabinoid receptor, exhibited an anti-proliferative action on EFM-19 cells at higher concentrations than arachidonoylethanolamide (IC50 = 11.3 microM for oleamide and 2.1 microM for arachidonoylethanolamide), while at a low, inactive dose it potentiated an arachidonoylethanolamide cytostatic effect. The CB1 receptor selective antagonist SR 141716A (0.5 microM) reversed the effect of both arachidonoylethanolamide and oleamide. EFM-19 cells and PC-12 cells were found to contain a membrane-bound [14C]arachidonoylethanolamide-hydrolysing activity with pH dependency and sensitivity to inhibitors similar to those previously reported for fatty acid amide hydrolase. This enzyme was inhibited by oleamide in both intact cells and cell-free preparations. The presence of transcripts of fatty acid amide hydrolase in these cells was shown by northern blot analyses of their total RNA. The rate of [14C]arachidonoylethanolamide hydrolysis by intact cells, the kinetic parameters of arachidonoylethanolamide enzymatic hydrolysis and the amounts of the fatty acid amide hydrolase transcript, were not significantly influenced by a two-week treatment with nerve growth factor and subsequent transformation of PC-12 cells into neuron-like cells. These data show for the first time that: (a) induction by nerve growth factor of a sympathetic neuronal phenotype in PC-12 cells has no effect on arachidonoylethanolamide/oleamide metabolism, (b) arachidonoylethanolamide and oleamide are autacoid suppressors of human breast cancer cell proliferation. Moreover these data lend conclusive support to the previous hypothesis that oleamide may act as an enhancer of arachidonoylethanolamide actions through competitive inhibition of its degradation.
Amidohydrolases↗
Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand.
Two endogenous ligands for cannabinoid receptors, anandamide (arachidonylethanolamide) and 2-arachidonoylglycerol, lose their biological activities by enzymatic hydrolysis. A cDNA for a rat liver enzyme hydrolyzing anandamide as well as oleamide was overexpressed in COS-7 cells. When the particulate fraction was allowed to react with 2-arachidonoylglycerol, arachidonic acid was produced. In contrast, this hydrolytic reaction did not occur with the control cells. The hydrolysis of 2-arachidonoylglycerol proceeded about 4-fold faster than the anandamide hydrolysis with a Km value as low as 6 microM and an optimal pH of 10. Phenylmethylsulfonyl fluoride and methyl arachidonyl fluorophosphonate inhibited the hydrolysis of both anandamide and 2-arachidonoylglycerol in parallel. Furthermore, the hydrolysis of [14C]2-arachidonoylglycerol was inhibited by anandamide dose-dependently. These results suggest that anandamide and 2-arachidonoylglycerol can be inactivated by the same enzyme.
Amidohydrolases↗
ABO-incompatible living related liver transplantation for fulminant hepatitis: report of a successful pediatric case with long-term follow-up.
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ABO Blood-Group System↗
Deterministic annealing EM algorithm.
This paper presents a deterministic annealing EM (DAEM) algorithm for maximum likelihood estimation problems to overcome a local maxima problem associated with the conventional EM algorithm. In our approach, a new posterior parameterized by `temperature' is derived by using the principle of maximum entropy and is used for controlling the annealing process. In the DAEM algorithm, the EM process is reformulated as the problem of minimizing the thermodynamic free energy by using a statistical mechanics analogy. Since this minimization is deterministically performed at each temperature, the total search is executed far more efficiently than in the simulated annealing. Moreover, the derived DAEM algorithm, unlike the conventional EM algorithm, can obtain better estimates free of the initial parameter values. We also apply the DAEM algorithm to the training of probabilistic neural networks using mixture models to estimate the probability density and demonstrate the performance of the DAEM algorithm.
Journal Article↗
Measurement of hepatocyte growth factor in serum and bronchoalveolar lavage fluid in patients with pulmonary fibrosis.
The present study evaluated the clinical significance of hepatocyte growth factor (HGF) in patients with pulmonary fibrosis. Twenty-one patients with a diagnosis of pulmonary fibrosis [14 with idiopathic pulmonary fibrosis (IPF) and seven with pulmonary fibrosis associated with a collagen vascular disorder (PF-CVD]) and 21 normal subjects as control were studied. HGF levels in sera of patients with pulmonary fibrosis (0.34 +/- 0.02 ng ml-1) were elevated significantly as compared with normal subjects (0.21 +/- 0.01 ng ml-1) (P < 0.0001). HGF/albumin levels in broncho-alveolar lavage fluid (BALF) of patients with pulmonary fibrosis (72 +/- 17 ng g-1 albumin) were also significantly elevated as compared with normal subjects (under the detection limit) (P < 0.01). HGF levels in sera correlated significantly with elastase levels in sera and C-reactive protein, and correlated negatively with PaO2. HGF levels in sera were significantly higher in smokers with pulmonary fibrosis (0.42 +/- 0.03 ng ml-1) as compared with non-smokers with pulmonary fibrosis (0.29 +/- 0.03 ng ml-1) (P < 0.005). HGF/albumin levels in BALF correlated significantly with elastase/albumin levels in BALF, lactate dehydrogenase/albumin in BALF, Immunoglobulin A/albumin in BALF, total cell count/albumin in BALF, total number of alveolar macrophage/albumin in BALF, total number of neutrophil/albumin in BALF, CEA/albumin in BALF, CA19-9/albumin in BALF, and SCC/albumin in BALF. These results suggest that following lung injury, HGF may be a mediator involved in the repair which leads to pulmonary fibrosis.
Adult↗
Role of enhanced ceramide generation in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells.
BACKGROUND: Ceramide has been implicated to be a second messenger in the cell signaling pathway involved in cell growth, proliferation, and apoptotic cell death. However, there is little information of a role of ceramide in DNA damage and cell death in hypoxic injury known to induce necrotic cell death. METHODS: Ceramide generation was measured in LLC-PK1 cells exposed to chemical hypoxia with a mitochondrial electron transport inhibitor, antimycin A and glucose deprivation. The effect of inhibition of ceramide generation on chemical hypoxia-induced DNA damage and cell death and the effect of exogenous ceramide on cellular injury were also determined. RESULTS: Chemical hypoxia resulted in a rapid increase in ceramide production prior to any evidence of DNA damage and cell death in LLC-PK1 cells. The inhibitor of ceramide synthase, fumonisin B1, provided a marked protection against chemical hypoxia-induced DNA strand breaks, DNA fragmentation and cell death. Fumonisin B1 did not affect adenosine triphosphate (ATP) depletion induced by antimycin A, suggesting that fumonisin B1 does not alter cellular uptake of antimycin A. We confirmed the ability of ceramide synthase inhibitor, fumonisin B1, to suppress chemical hypoxia-induced ceramide generation. Exposure of LLC-PK1 cells to synthetic ceramide, C2- and C6-ceramide, but not C2-dihydroceramide, the structural analog of C2-ceramide, resulted in DNA strand breaks, DNA fragmentation and cell death in a dose- and time-dependent manner similar to the effect of chemical hypoxia. CONCLUSIONS: Our data indicate that ceramide is a key modulator for DNA damage and cell death in chemical hypoxia to renal tubular epithelial cells.
Animals↗
Role of cytochrome P-450 as a source of catalytic iron in cisplatin-induced nephrotoxicity.
BACKGROUND: Iron plays a role in free radical-mediated tissue injury, including cisplatin-induced nephrotoxicity. However, the source of iron (catalyzing free radical reactions) is not known. We examined the role of cytochrome P-450 as a source of catalytic iron in cisplatin-induced nephrotoxicity both in vivo and in vitro. METHODS: Cisplatin-induced acute renal failure was produced in rats by intraperitoneal injection of cisplatin (10 mg/kg body wt). Piperonyl butoxide, a cytochrome P-450 inhibitor, was administered intraperitoneally (400 mg/kg body wt twice at 48-hr intervals) prior to cisplatin injection. The effects of cisplatin in the absence or presence of piperonyl butoxide on the belomycin-detectable iron, cytochrome P-450 content in the kidney, and renal functional and histological changes were evaluated. In an in vitro study, the effect of cytochrome P-450 inhibitors, cimetidine or piperonyl butoxide, on cisplatin-induced cytotoxicity and catalytic iron release from LLC-PK1 cells was examined. RESULTS: In cisplatin-treated rats, there was a marked decrease in the cytochrome P-450 content specifically in the kidney, accompanied by increased bleomycin-detectable iron content in the kidney. Piperonyl butoxide prevented cisplatin-induced loss of cytochrome P-450 as well as the increase of bleomycin-detectable iron in the kidney, along with both functional and histological protection. Both cimetidine and piperonyl butoxide prevented cisplatin-induced increase in bleomycin-detectable iron and cytotoxicity in LLC-PK1 cells. Treatment of cimetidine did not affect cellular uptake of cisplatin. CONCLUSION: Cytochrome P-450, a group of heme proteins, may serve as a significant source of catalytic iron in cisplatin-induced nephrotoxicity.
Animals↗
In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity.
Cisplatin is a widely used antineoplastic agent that has nephrotoxicity as a major side effect. The underlying mechanism of this nephrotoxicity is still not well known. Iron has been implicated to play an important role in several models of tissue injury, presumably through the generation of hydroxyl radicals via the Haber-Weiss reaction or other highly toxic free radicals. In the present study we examined the catalytic iron content and the effect of iron chelators in an in vitro model of cisplatin-induced cytotoxicity in LLC-PK1 cells (renal tubular epithelial cells) and in an in vivo model of cisplatin-induced acute renal failure in rats. Exposure of LLC-PK1 cells to cisplatin resulted in a significant increase in bleomycin-detectable iron (iron capable of catalyzing free radical reactions) released into the medium. Concurrent incubation of LLC-PK1 cells with iron chelators including deferoxamine and 1,10-phenanthroline significantly attenuated cisplatin-induced cytotoxicity as measured by lactate dehydrogenase (LDH) release. Bleomycin-detectable iron content was also markedly increased in the kidney of rats treated with cisplatin. Similarly, administration of deferoxamine in rats provided marked functional (as measured by blood urea nitrogen and creatinine) and histological protection against cisplatin-induced acute renal failure. In a separate study, we examined the role of hydroxyl radical in cisplatin-induced nephrotoxicity. Incubation of LLC-PK1 cells with cisplatin caused an increase in hydroxyl radical formation. Hydroxyl radical scavengers, dimethyl sulfoxide, mannitol and benzoic acid, significantly reduced cisplatin-induced cytotoxicity and, treatment with dimethyl sulfoxide or dimethylthiourea provided significant protection against cisplatin-induced acute renal failure. Taken together, our data strongly support a critical role for iron in mediating tissue injury via hydroxyl radical (or a similar oxidant) in this model of nephrotoxicity.
Acute Kidney Injury↗
Clinical evaluation of a portable digital hearing aid with narrow-band loudness compensation.
A new portable digital hearing aid referred to as CLAIDHA (Compensate for Loudness by Analyzing Input-signal Digital Hearing Aid), which employs frequency-dependent amplitude compression based on narrow-band loudness compensation, was clinically evaluated in 159 subjects with hearing loss. The results of speech tests revealed better intelligibility compared with the subject's own hearing aids; the advantage of using CLAIDHA in daily life was also indicated by the results of a questionnaire completed by the subjects. In about 64% of the subjects with a flat, gradually sloping type of hearing loss, CLAIDHA was satisfactorily adopted for daily use. However, in the subjects with a steeply sloping type of hearing loss and subjects with losses mainly at high and low frequencies, with near-normal mid-frequency hearing. this loudness compensation scheme seems to be slightly less effective.
Aged↗
Activin A regulates the production of mature interleukin-1beta and interleukin-1 receptor antagonist in human monocytic cells.
Activin A, a member of the transforming growth factor-beta (TGF-beta) family, is produced by a variety of cells and implicated in the regulation of the reproductive endocrine system, mesoderm induction, and erythropoiesis. In the present study, we showed that activin A inhibited the production of interleukin-1beta (IL-1beta), a potent proinflammatory cytokine, and enhanced the production of IL-1 receptor antagonist (IL-1ra), in activated THP-1 and U-937 human monocytic cells, resulting in the reduction of IL-1 biologic activity. Northern blot analysis revealed that activin A had no effect on mRNA accumulation of IL-1beta and IL-1ra, indicating that activin A regulates IL-1beta and IL-1ra production at a posttranscriptional level. As it is well known that an inactive precursor form of IL-1beta (pro-IL-1beta) is converted to an active mature form (mature IL-1beta), we examined the expression levels of pro-IL-1beta and mature IL-1beta by immunoblot analysis. Although activin A inhibited the production of mature IL-1beta in activated U-937 cells, the relative protein expression of pro-IL-1beta was unaltered by activin A, suggesting that activin A inhibits IL-1beta production by blocking proteolytic conversion of pro-IL-1beta into mature IL-1beta. Taken together, these findings suggest that activin A may function as an anti-inflammatory cytokine by modulating mature IL-1beta and IL-1ra production in inflammatory sites.
Activins↗
Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.
BACKGROUND: Activation and consequent phenotypic modulation of mesangial cells is considered to play a crucial role in the process of glomerular disease progression. Caldesmon, a calmodulin and actin-binding protein, is a molecular marker of the phenotypic change in smooth-muscle cells. SUBJECTS AND METHODS: We studied whether the expression of caldesmon in mesangial cells was enhanced in the process of IgA nephropathy and whether it would be a marker of mesangial activation indicating prognostic significance in specific disease states. We performed immunohistochemical staining with anticaldesmon and alpha-smooth-muscle actin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. RESULTS: The glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We compared caldesmon expression with composite histological scores (cell score and matrix score), clinical parameters and expressions of alpha-SMA. There was a statistically significant correlation between the caldesmon score and the histological scores (cell score and matrix score, P<0.0001, P<0.01 respectively). Patients showing a high intensity of caldesmon expression (defined as caldesmon score > or = 35; H-group) had significantly higher urinary protein excretion than those showing a low intensity of caldesmon expression (defined as caldesmon score < 35; L-group) (1.2 +/- 1.2 g/24 h vs 0.41 +/- 0.53 g/24 h, P<0.05). Caldesmon and alpha-SMA expression had a statistically significant correlation (P<0.000). Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks and re-biopsies were performed. After the therapy, the caldesmon and alpha-SMA scores were significantly lower than those before the therapy (P<0.01). DISCUSSION: These results suggest that the expression of caldesmon in glomeruli is associated with the progression of IgA nephropathy, and that glucocorticoid heparin therapy may reverse the phenotype of mesangial cells during the disease process of glomerulonephritis.
Actins↗
Pulmonary arterial and right ventricular responses to prophylactic albumin administration before aortic unclamping during abdominal aortic aneurysmectomy.
UNLABELLED: During abdominal aortic aneurysmectomy (AAAectomy) and before aortic unclamping (XU), we studied the effects of albumin administration on pulmonary arterial and right ventricular responses in 39 anesthetized patients using a modified thermodilution technique. Group 1 patients (n = 18) were given no extra IV fluids. Group 2 patients (n = 21) were given additional albumin administration (5% albumin at 10 mL/kg) before XU. After XU, mean arterial blood pressure (MAP) decreased significantly in each group, and MAP and stroke volume index (SVI) were not significantly higher in Group 2 than in Group 1. At 5 min after XU, the patients in Group 2 had a higher mean pulmonary arterial pressure and pulmonary vascular resistance index and a lower right ventricular ejection fraction than those in Group 1 (P < 0.05), but their SVIs were well maintained. These results indicate that albumin administration before XU may not always prevent post-XU hypotension. It caused a significant increase in right ventricular afterload and a significant dilation of the right ventricular cavity; however, right ventricular function was almost equally maintained in both groups. However, because SVI did not increase in some patients (Group 2) with the increase in right ventricular end-diastolic volume index after XU, albumin administration should be performed carefully before XU during AAAectomy. IMPLICATIONS: We studied the effects of albumin administration before aortic unclamping on pulmonary arterial and right ventricular responses during abdominal aortic aneurysmectomy using a modified thermodilution technique. Albumin administration before aortic unclamping may not always prevent hypotension, and it may cause a higher pulmonary arterial pressure than in patients without albumin administration.
Aged↗
Mitochondrial DNA deletion is a predisposing cause for sensorineural hearing loss.
Composed of a postmitotic stable tissue, the inner ear is a target organ for mitochondrial DNA (mtDNA) mutation. To determine whether mtDNA mutation is a predisposing factor in patients with sensorineural hearing loss (SNHL), the authors assessed the mtDNA4977 deletion from 60 patients with SNHL and 47 normal control subjects. All cases had no past history of ototoxic or noise exposure, middle ear disease, or other known etiological factors for SNHL. DNA specimens extracted from peripheral blood leukocytes were used for detection of mtDNA4977 deletion by polymerase chain reaction. Patients with SNHL had a significantly higher rate of the mtDNA4977 deletion than did controls (75% vs. 30%, P < 0.0001). The detection rate of mtDNA4977 deletion was significantly increased with the deterioration of the hearing threshold. Aging did not influence the detection rate of mtDNA4977 deletion in either the control or SNHL group. The authors have described high detection rates of the mtDNA4977 deletion in patients with idiopathic bilateral SNHL and propose that at least some of the advanced SNHL cases should be categorized as mitochondrial oxidative phosphorylation diseases. This inference would offer novel possibilities for treatment and prevention of SNHL including presbycusis.
Adult↗