A novel missense mutation Thr316Ala in lysosomal acid lipase gene in Japanese population.
Explore the source record for details and available documents.
Alanine↗
Biomedical subjects
T Egashira
Publications and source records attributed to T Egashira.
Mutation analysis of iduronate-2-sulphatase gene in 24 patients with Hunter syndrome: characterisation of 6 novel mutations. Mutation in brief no. 249. Online.
Hunter syndrome is a rare, X-linked, recessively inherited disease affecting approximately 1 in 132,000 males. The disease is caused by the inability to degrade dermatan sulphate and heparan sulphate due to mutations in the iduronate-2-sulphatase gene (IDS). The mutations causing the disorder are heterogeneous, ranging from small micro-lesions to gross deletions and inversions. We have screened DNA samples from a panel of 24 unrelated Hunter syndrome patients and have identified mutations in 16 individuals. Six mutations represent novel changes in the gene and these include two single base deletions (1264DC and 1632/3DT); two single base insertions (776/8insC and 1082insT); and two missense mutations--Y264N (914T-->G) and Q465P (1518A-->C). An additional two missense mutations and one splice site alteration identified in this study have been described previously. Southern analysis revealed complete or partial gene deletions in a further 7 patients.
DNA Mutational Analysis↗
Changes in monoamine metabolites concentrations in rat cerebrospinal fluid after acute and long-term administration of a selective serotonin reuptake inhibitor, trazodone.
In order to clarify the mechanism of the antidepressive effects of trazodone, a selective serotonin reuptake inhibitor, we investigated the dynamics of monoamine metabolites in cerebrospinal fluid (CSF) of free-moving conscious rats by acute and long-term treatment with trazodone. When 100 mg kg-1 p.o. of trazodone were administered, a significant increase of 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration was soon observed in the light period of the light/dark cycle, and a significant decrease of dihydroxy phenyl acetic acid (DOPAC) concentration was observed during the 2 days after administration of trazodone; in contrast, the homovanilic acid (HVA) level was increased. However, we detected no significant changes in the 5-hydroxy indole-3-acetic acid (5-HIAA) concentration during the 3 days. In the case of long-term treatment with 50 mg kg-1, p.o. of trazodone, the levels of MHPG, DOPAC and HVA exhibited no difference when compared with values obtained during saline treatment in either the light or dark period, whereas the levels of 5-HIAA showed a significant increase during the light period. These findings suggest that a long-term treatment with trazodone enhances the serotonergic neurons.
3,4-Dihydroxyphenylacetic Acid↗
Age-related changes in alpha-tocopherol dynamics with relation to lipid hydroperoxide content and fluidity of rat erythrocyte membrane.
Age-related changes in alpha-tocopherol dynamics in plasma and erythrocyte membranes of 10- to 120-week-old rats were investigated by high-performance liquid chromatography (HPLC) with redox detection mode. Furthermore, changes in lipid hydroperoxide content and fluidity of erythrocyte membrane with age were assessed using chemiluminescence-HPLC and Fourier transform infrared spectrophotometer, respectively. A slight increase in the alpha-tocopherolquinone/alpha-tocopherol ratio in erythrocyte membrane and a decrease in the alpha-tocopherol in erythrocyte membrane/alpha-tocopherol in plasma ratio were observed. A significant increase in lipid hydroperoxide content and a marked decrease in the fluidity of erythrocyte membrane were seen with age. These findings suggest that alpha-tocopherol uptake in erythrocyte membrane declines, and utilization rate of alpha-tocopherol in erythrocyte membrane increases age-dependently. These changes, which enhanced lipid peroxidation and consequently reduced membrane fluidity, may be caused by the impairment of this transfer mechanism.
Aging↗
Monitoring of radical scavenging activity of peroral administration of the Kampo medicine Sho-saiko-to in rats.
The Kampo medicine Sho-saiko-to scavenged superoxide anion radicals (O2-), hydroxyl radicals (*OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals in a dose-dependent fashion. We attempted to investigate the transition of free radical scavenging activity in plasma after oral administration of Sho-saiko-to in rats. From the response-time profile, kinetic parameters including values for Ka (absorption rate constant), Tmax (peak concentration time), T1/2 (half life) and MRT (mean residence time) of radical scavenging activity in plasma could be calculated for the O2-, *OH and DPPH radicals. These parameters calculated from the dynamics of antioxidation are considered a very meaningful procedure to examine the effects of Sho-saiko-to.
Animals↗
The inhibition of monoamine oxidase activity by various antidepressants: differences found in various mammalian species.
The effects of the antidepressant drugs zimeldine, imipramine, maprotiline or nomifensine on mitochondrial monoamine oxidase (MAO) activity in mouse, rat, dog and monkey brains were compared in vitro. Mouse, rat, dog and monkey brain MAO-B activities were inhibited by zimeldine more potently than MAO-A activity. Imipramine inhibited MAO-B more potently than MAO-A activity in mouse and rat brains. When dog and monkey brains were investigated, MAO-A activity was inhibited more potently than MAO-B activity at high concentrations of imipramine, while at low concentrations, MAO-B activity was more potently inhibited. Maprotiline and nomifensine inhibited mouse and rat brain MAO-B activity more potently than MAO-A activity, while the inverse was true for dog and monkey brains. All four drugs are competitive inhibitors of MAO-A, but noncompetitive inhibitors of MAO-B in all animal brains. The respective Ki values of these reagents for monkey brain MAO-A and MAO-B were low compared to those of mouse, rat and dog. These results indicate that monkey brain MAOs are more sensitive to antidepressant drugs than those in rodent brain.
Animals↗
NO contribution to lipopolysaccharide-induced hepatic damage in galactosamine-sensitized mice.
To investigate the role of nitric oxide (NO) in hepatitis-induced endotoxemia, we injected mice intraperitoneally with 250 mg/kg galactosamine (GalN) and 1 mg/kg lipopolysaccharide (LPS) separately and in combination. NO synthesis increased in a dose-dependent manner with LPS. NO generation at 5 hr after administration of LPS was greater than that at 24 hr. Enhancement of NO generation was demonstrated in mice administered GalN and LPS in combination. A nitrosyl-heme signal in 10,000 g supernatant of liver homogenate, due to cytochrome P450 (P450) combining with NO, NO-P450, was detected at more than ten hr and even more after administration of LPS by electron spin resonance (ESR) measurements at 77 degrees K. The strongest NO-P450 signal and most extreme elevation of aspartate oxoglutarate aminotransferase (AST), alanine oxoglutarate aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum and of lysosomal enzyme activity in plasma were observed in the GalN + LPS group. Their potency was greater than in the 10 mg/kg LPS group, which was even greater than in the LPS 1 mg/kg group. The aniline hydroxylase activity was inversely proportional to NO-P450 signal intensity. It appears that NO might contribute to LPS-induced hepatic damage in GalN-sensitized mice through degeneration and inactivation of liver microsomal enzymes by binding P450 active sites.
Aniline Hydroxylase↗
[Alterations in neurotransmitter, amino acid and free radical related substances in cerebrospinal fluid in patients with cerebrovascular diseases].
Acetylcholinesterase (AChE), choline, monoamine and its metabolite, amino acid and superoxide dismutase (SOD) levels were measured in cerebrospinal fluid (CSF) in patients with cerebrovascular diseases. Patients were classified into the following four groups; controls: normal subjects without neurological disease, group A: cerebral hemorrhage, group B: cerebral infarction, group C: patients with mental impairment, including those in groups A and B, and a low score on Hasegawa's Dementia Rating Scale. CSF AChE level of groups A, B and C was decreased significantly, while choline concentration from patients showed a increase compared with that of control cases. CSF alanine concentration showed a tendency to increase, while glycine and glutamate tended to decrease. CSF epinephrine, norepinephrine or 3-methoxy-4-hydroxyphenylethylen glycol concentrations of groups A, B and C did not exhibit a significant difference from that in control cases. Some cases with cerebrovascular diseases showed low concentrations of both CSF 5-hydroxyindole acetic acid and homovanillic acid. However, dihydroxyphenyl acetic acid concentration was higher than in control cases. The CSF SOD level was not significantly from that in control cases. The changes in neurochemical substances in the CSF support their use as markers of cerebrovascular disease-related change.
Acetylcholinesterase↗
Phospholipid transfer protein (PLTP) causes proteolytic cleavage of apolipoprotein A-I.
Plasma phospholipid transfer protein (PLTP) is a factor that plays an important role in HDL metabolism. In this study we present data suggesting that PLTP has an inherent protease activity. After incubation of HDL3 in the presence of purified plasma PLTP, the d < 1.25 g/ml particles (fusion particles) contained intact 28.2 kDa apoA-I while the d > 1.25 g/ml fraction (apoA-I-PL complexes) contained, in addition to intact apoA-I, a cleaved 23 kDa form of apoA-I. Purified apoA-I was also cleaved by PLTP and produced a similar 23 kDa apoA-I fragment. The cleavage of apoA-I increased as a function of incubation time and the amount of PLTP added. The process displayed typically an 8-10 h lag or induction period, after which the cleavage proceeded in a time-dependent manner. This lag-phase was necessary for the development of the cleavage activity during incubation at 37 degrees C. The specific apoA-I cleavage activity of different PLTP preparations varied between 0.4-0.8 microg apoA-I degraded/h per 1000 nmol per h of PLTP activity. The 23 kDa apoA-I fragment reacted with monoclonal antibodies specific for the N-terminal part of apoA-I, indicating that the apoA-I cleavage occurred in the C-terminal portion. The apoA-I cleavage products were further characterized by mass spectrometry. The 23 kDa fragment yielded a mass of 22.924 kDa, demonstrating that the cleavage occurs in the C-terminal portion of apoA-I between amino acid residues 196 (alanine) and 197 (threonine). The intact apoA-I and the 23 kDa fragment revealed identical N-terminal amino acid sequences. The cleavage of apoA-I could be inhibited with APMSF and chymostatin, suggesting that it is due to a serine esterase-type of proteolytic activity. Recombinant PLTP produced in CHO cells or using the baculovirus-insect cell system caused an apoA-I cleavage pattern identical to that obtained with plasma PLTP. The present results raise the question of whether PLTP-mediated proteolytic cleavage of apoA-I might affect plasma HDL metabolism by generating a novel kinetic compartment of apoA-I with an increased turnover rate.
Amino Acid Sequence↗
Cloning of a Sphingomonas paucimobilis SYK-6 gene encoding a novel oxygenase that cleaves lignin-related biphenyl and characterization of the enzyme.
Sphingomonas paucimobilis SYK-6 transforms 2,2'-dihydroxy-3,3'-dimethoxy-5,5'-dicarboxybiphenyl (DDVA), a lignin-related biphenyl compound, to 5-carboxyvanillic acid via 2,2',3-trihydroxy-3'-methoxy-5,5'-dicarboxybiphenyl (OH-DDVA) as an intermediate (15). The ring fission of OH-DDVA is an essential step in the DDVA degradative pathway. A 15-kb EcoRI fragment isolated from the cosmid library complemented the growth deficiency of a mutant on OH-DDVA. Subcloning and deletion analysis showed that a 1.4-kb DNA fragment included the gene responsible for the ring fission of OH-DDVA. An open reading frame encoding 334 amino acids was identified and designated ligZ. The deduced amino acid sequence of LigZ had 18 to 21% identity with the class III extradiol dioxygenase family, including the beta subunit (LigB) of protocatechuate 4,5-dioxygenase of SYK-6 (Y. Noda, S. Nishikawa, K.-I. Shiozuka, H. Kadokura, H. Nakajima, K. Yano, Y. Katayama, N. Morohoshi, T. Haraguchi, and M. Yamasaki, J. Bacteriol. 172:2704-2709, 1990), catechol 2,3-dioxygenase I (MpcI) of Alcaligenes eutrophus JMP222 (M. Kabisch and P. Fortnagel, Nucleic Acids Res. 18:3405-3406, 1990), the catalytic subunit of the meta-cleavage enzyme (CarBb) for 2'-aminobiphenyl-2,3-diol from Pseudomonas sp. strain CA10 (S. I. Sato, N. Ouchiyama, T. Kimura, H. Nojiri, H. Yamane, and T. Omori, J. Bacteriol. 179:4841-4849, 1997), and 2,3-dihydroxyphenylpropionate 1,2-dioxygenase (MhpB) of Escherichia coli (E. L. Spence, M. Kawamukai, J. Sanvoisin, H. Braven, and T. D. H. Bugg, J. Bacteriol. 178:5249-5256, 1996). The ring fission product formed from OH-DDVA by LigZ developed a yellow color with an absorption maximum at 455 nm, suggesting meta cleavage. Thus, LigZ was concluded to be a ring cleavage extradiol dioxygenase. LigZ activity was detected only for OH-DDVA and 2,2',3,3'-tetrahydroxy-5,5'-dicarboxybiphenyl and was dependent on the ferrous ion.
Amino Acid Sequence↗
Role of superoxide dismutase in otitis media with effusion.
The concentration of superoxide dismutase (SOD) in middle ear effusion (MEE) was measured by the electron spin resonance trapping method in order to clarify the role of SOD in otitis media with effusion (OME) in children. The SOD levels in mucoid MEEs were significantly higher than those in serous and purulent MEEs. There was no significant difference in the levels of SOD between neutrophil-dominant MEEs and mononuclear cell-dominant MEEs, and the levels were negatively correlated with the number of neutrophils in the MEEs. Moreover, the levels were significantly increased in patients having recurrence of MEE within 3 months compared with patients without recurrence of MEE. Although it is known that SOD plays an important role in protecting the host from oxygen radicals, the findings in this study suggest that SOD might be related to the chronicity of OME.
Adolescent↗
[Assay for oxidative stress injury by detection of luminol-enhanced chemiluminescence in a freshly obtained blood sample: a study to follow the time course of oxidative injury].
To evaluate occurrence of oxidative stress in circulating blood, we developed standard methods to assess (1) granulocytes status as a source of reactive oxygen species (ROS) and (2) lipid peroxidation (LPO). A simplified and highly sensitive assay was developed by utilizing the chemiluminescence (CL) from luminol oxidized by ROS. 1. The CL, from 300 microliters medium containing 1% blood, 10 micrograms/ml luminol and 0.025 microgram/ml phorbol myristate acetate, well reflected the primed granulocyte status induced by in vitro contact with lipopolysaccharide (LPS). This CL was weakened slightly by superoxide dismutase and catalase, but markedly decreased by sodium azide. 2. We determined the optimal conditions for the t-butyl hydroperoxide (t-BuOOH)-stimulated CL method to evaluate plasma LPO in experiments on rat plasma added with phosphatidylethanolamine hydroperoxide (PEOOH). The CL from 300 microliters medium containing 6.67% plasma. 10 micrograms/ml luminol and 5 mumol/ml t-BuOOH was proportional to the added PEOOH amount. The integrated CL of the plasma with 0-60 nmol of PEOOH gave values of 8.280-14.213 x 10(6) counts/60 min/tube. 3. Only 100 microliters of freshly drawn blood was enough for the two CL methods to detect the generation of ROS and the occurrence of LPO. These CL methods enabled the determination of the time course of oxidative stress occurrence in circulating blood of rats treated with 5 mg/kg LPS, i.p.
Animals↗
Variation of monoamines and their metabolite contents in the cerebrospinal fluid of conscious rats.
To study the circadian rhythm of the monoamine and metabolite contents, cerebrospinal fluid was taken from the cisterna magna through a polyethylene catheter tube every 4 hr in the conscious rat. Norepinephrine and 3-methoxy-4-hydroxy-phenylglycol were found to describe a rhythm with the maximal content occurring during the dark phase and the minimal content occurring during the light phase. Dopamine levels increased significantly during the light phase compared with the dark phase. These results, given that cerebrospinal fluid can be taken chronically from conscious rats, indicate that our present method may be suitable for estimating changes in brain monoamine and metabolite contents.
3,4-Dihydroxyphenylacetic Acid↗
[Detection and characterization of free radicals, radical scavenging activity, and lipid peroxides in cerebral ischemia-reperfusion injury by electron spin resonance and chemiluminescence high-performance liquid chromatography].
During the ischemia-reperfusion period, the hypoxanthine-xanthine oxidase system simultaneously generates superoxide (O2-). O2- has an extremely short half-life, as it rapidly undergoes Fenton-type reactions in the presence of iron and yields highly cytotoxic hydroxyl radicals (.OH). Oxygen-derived free radicals are induced as a contributing cause of cellular injury in several neurological disorders, including cerebral infarction and aging. Cerebral injury by ischemia-reperfusion following middle cerebral artery occlusion could be useful experimental model for studying cerebral injury induced by free radicals. Thiobarbituric acid reactants generally indicate lipid peroxidation associated with cellular damage caused by free radicals. Phosphatidylethanolamine hydroperoxide (PEOOH) is the primary peroxidative product of phosphatidylethanolamine, which is the most important functional lipid in the membrane. Plasma PEOOH levels appear to be a reliable indicator of cerebral damage caused by ischemia-reperfusion and other oxidative stress. Recently, an electron spin resonance (ESR) spectrometer was used in the detection of free radicals, in vivo and in vitro using 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) as the radical-trapping reagent. Moreover, there are reports the electron spin resonance-computed tomography (ESR-CT) images of the cephalic region of rats for locating regions of pathological change are related to free radicals in the brain.
Animals↗
Effects of long-term treatment with dicyclic, tricyclic, tetracyclic, and noncyclic antidepressant drugs on monoamine oxidase activity in mouse brain.
1. The individual long-term effects of the antidepressant drugs zimeldine, viloxazine, imipramine, amitriptyline, nortriptyline, maprotiline, or nomifensine, on brain mitochondrial monoamine oxidase (MAO) activity, were studied in mice that were given daily intraperitoneal injections (30 mg/kg) of these reagents for 4 weeks. 2. Both the A-form (MAO-A) and B-form (MAO-B) of MAO were inhibited after long-term administration of all the drugs except nortriptyline (MAO-A was not affected) and maprotiline (neither MAO-A nor MAO-B were affected). 3. Kinetic analysis showed a significant decrease in Vmax values, and an increase in K(m) values for MAO-B during treatment. 4. All seven drugs are competitive inhibitors of MAO-A, noncompetitive inhibitors of MAO-B, and were more potent in vitro for MAO-B. 5. MAO-A was inhibited by the following drugs (in ascending order of potency) : nortriptyline, amitriptyline, imipramine, maprotiline, zimeldine, nomifensine, and viloxazine. 6. MAO-B was inhibited by the following drugs (in ascending order of potency): nortriptyline, imipramine, maprotiline, amitriptyline, zimeldine, nomifensine, and viloxazine.
Animals↗
Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres, protects injury of the liver caused by warm ischemia reperfusion.
Effects of Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres on liver injury caused by ischemia reperfusion were investigated. Lipo-PGE1 (10 micrograms/kg or 3 micrograms/kg) or vehicle was gradually injected twice via portal vein 5 min prior to induction of ischemia and reperfusion. Rats died within 2 d after liver ischemia of 90 min from the group receiving injection of vehicle alone. Lipo-PGE1 had its most profound effect on the survival of animals subjected to liver ischemia followed by reperfusion when given in two doses, one prior to ischemia, and another prior to reperfusion. Lipo-PGE1 markedly suppressed both the increases in plasma PCOOH (phosphatidyl-choline hydroperoxide) levels and the leakage of GOT, GPT, and LDH from the liver during the ischemia reperfusion. These findings suggest that Lipo-PGE1 may have therapeutic applications in treatment of hepatic injury.
Alanine Transaminase↗
Effect of fluvoxamine on 5-hydroxytryptamine uptake, paroxetine binding sites and ketanserin binding sites in the Japanese monkey brain and platelets, in vivo and in vitro.
We investigated the in vitro effects of fluvoxamine on 3H-paroxetine binding and 3H-monoamine uptake in monkey cerebral cortex in comparison with those of other antidepressants. Fluvoxamine selectively inhibited 3H-5-hydroxytryptamine (5-HT) uptake and 3H-paroxetine binding. However, it did not alter 3H-norepinephrine or 3H-dopamine uptake. In addition, we examined the effects of chronic treatment with fluvoxamine (5 mg/kg per day, p.o.) on 5-HT uptake sites that bind 3H-paroxetine and 5-HT2 receptors that bind 3H-ketanserin, in monkey brains and platelets. Chronic treatment with fluvoxamine affected neither the paroxetine binding sites nor the kentanserin binding sites of the brains and platelets. These results suggest that long-term treatment with fluvoxamine does not affect either the 5-HT uptake sites or 5-HT2-receptors of 5-HT neurons in monkey brain in spite of its strong inhibitory effect on 5-HT uptake in vitro.
Animals↗
Effects of bifemelane on muscarinic receptors and choline acetyltransferase in the brains of aged rats following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries.
Cerebral hypoperfusion was chronically induced in aged rats via permanent bilateral occlusion of common carotid arteries (2VO). Marked reduction of the Bmax value of the muscarinic receptors (mAChR) in both the cortex and striatum and the Vmax value of choline acetyltransferase (ChAT) activity in the cortex, hippocampus and striatum were observed as compared with those of control aged rats. No significant changes in mAChR and ChAT activity were observed between young control rats and young 2VO rats. One month post-surgery in aged rats, daily doses of bifemelane (10 mg/kg) or aniracetam (50 mg/kg) were administered orally over a 4-week period. Administration of bifemelane significantly increased Bmax values and decreased apparent Kd values for 3H-quinuclidinyl benzilate (QNB) in mAChR in the striatum. Chronic administration of bifemelane or aniracetam also enhanced ChAT activity in the cortex, hippocampus and striatum. In particular, administration of bifemelane resulted in a significant increase in Vmax values of ChAT in all three brain regions, while no significant change in K(m) values for ChAT was observed. These results suggest that bifemelane is responsible for this activity, thereby enhancing the functioning system of CNS cholinergic neurons of cerebral hypoperfused aged rats.
Age Factors↗