Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 87
Filter
1.
Phys Rev E ; 109(1-1): 014903, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38366452

ABSTRACT

We experimentally investigate the dynamics of a sphere rolling up a granular slope. During the rolling-up motion, the sphere experiences slipping and penetration (groove formation) on the surface of the granular layer. The former relates to the stuck motion of the rolling sphere, and the latter causes energy dissipation due to the deformation of the granular surface. To characterize these phenomena, we measured the motion of a sphere rolling up a granular slope of angle α. The initial velocity v_{0}, initial angular velocity ω_{0}, angle of slope α, and density of the sphere ρ_{s} were varied. As a result, the penetration depth can be scaled solely by the density ratio between the sphere and granular layer. By considering the rotational equation of motion, we estimate the friction due to the slips. Besides, by considering energy conservation, we define and estimate the friction due to groove formation. Moreover, the translational friction is proportional to the penetration depth. Using these results, we can quantitatively predict the sphere's motion including stuck behavior.

2.
J Chem Phys ; 158(21)2023 Jun 07.
Article in English | MEDLINE | ID: mdl-37260007

ABSTRACT

In various types of many-particle systems, bidispersity is frequently used to avoid spontaneous ordering in particle configurations. In this study, the relation between bidispersity and disorder degree of particle configurations is investigated. By using magnetic dipole-dipole interaction, magnet particles are dispersed in a two-dimensional cell without any physical contact between them. In this magnetic system, bidispersity is introduced by mixing large and small magnets. Then, the particle system is compressed to produce a uniform particle configuration. The compressed particle configuration is analyzed by using Voronoi tessellation for evaluating the disorder degree, which strongly depends on bidispersity. Specifically, the standard deviation and skewness of the Voronoi cell area distribution are measured. As a result, we find that the peak of standard deviation is observed when the numbers of large and small particles are almost identical. Although the skewness shows a non-monotonic behavior, a zero skewness state (symmetric distribution) can be achieved when the numbers of large and small particles are identical. In this ideally random (disordered) state, the ratio between pentagonal, hexagonal, and heptagonal Voronoi cells becomes roughly identical, while hexagons are dominant under monodisperse (ordered) conditions. The relation between Voronoi cell analysis and the global bond orientational order parameter is also discussed.

3.
Neurotoxicology ; 45: 56-66, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25284465

ABSTRACT

Ziram is a dimethyldithiocarbamate fungicide which can cause intraneuronal calcium (Ca(2+)) dysregulation and subsequently neuronal death. The signaling mechanisms underlying ziram-induced Ca(2+) dyshomeostasis and neurotoxicity are not fully understood. NCX3 is the third isoform of the sodium-calcium exchanger (NCX) family and plays an important role in regulating Ca(2+) homeostasis in excitable cells. We previously generated a mouse model deficient for the sodium-calcium exchanger 3 and showed that NCX3 is protective against ischemic damage. In the present study, we aim to examine whether NCX3 exerts a similar role against toxicological injury caused by the pesticide ziram. Our data show baby hamster kidney (BHK) cells stably transfected with NCX3 (BHK-NCX3) are more susceptible to ziram toxicity than cells transfected with the empty vector (BHK-WT). Increased toxicity in BHK-NCX3 was associated with a rapid rise in cytosolic Ca(2+) concentration [Ca(2+)]i induced by ziram. Profound mitochondrial dysfunction and ATP depletion were also observed in BHK-NCX3 cells following treatment with ziram. Lastly, primary dopaminergic neurons lacking NCX3 (NCX3(-/-)) were less sensitive to ziram neurotoxicity than wildtype control dopaminergic neurons. These results demonstrate that NCX3 genetic deletion protects against ziram-induced neurotoxicity and suggest NCX3 and its downstream molecular pathways as key factors involved in ziram toxicity. Our study identifies new molecular events through which pesticides (e.g. ziram) can lead to pathological features of degenerative diseases such as Parkinson's disease and indicates new targets to slow down neuronal degeneration.


Subject(s)
Calcium/metabolism , Fungicides, Industrial/toxicity , Sodium-Calcium Exchanger/metabolism , Ziram/toxicity , Adenosine Triphosphate/analysis , Animals , Cell Death/drug effects , Cell Line , Cricetinae , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/drug effects , Sodium-Calcium Exchanger/genetics
4.
Transl Psychiatry ; 2: e178, 2012 Oct 23.
Article in English | MEDLINE | ID: mdl-23092982

ABSTRACT

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy ((1)H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=-0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher's r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=-3.23, P=0.001), which indicated that the age-NAA relationship was significantly specific to people with TD. The current (1)H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.


Subject(s)
Aging/metabolism , Aspartic Acid/analogs & derivatives , Asperger Syndrome/metabolism , Autistic Disorder/metabolism , Prefrontal Cortex/metabolism , Adult , Age Factors , Aspartic Acid/metabolism , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Multivariate Analysis
5.
AJNR Am J Neuroradiol ; 32(8): E150-2, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20864523

ABSTRACT

IgG4-related IPTs have been reported in various sites and may form part of the spectrum of systemic IgG4-related sclerosing disease. Some pseudotumors are clinically and radiologically indistinguishable from malignant tumors. We present the first case of an IgG4-related IPT of the trigeminal nerve diagnosed histopathologically without involvement of any of the common sites. The trigeminal nerve pseudotumor may represent a component of IgG4-related sclerosing disease.


Subject(s)
Granuloma, Plasma Cell/diagnosis , Immunoglobulin G , Scleroderma, Systemic/diagnosis , Trigeminal Nerve Diseases/diagnosis , Female , Granuloma, Plasma Cell/immunology , Humans , Middle Aged , Scleroderma, Systemic/immunology , Trigeminal Nerve Diseases/immunology
6.
Brain Res Mol Brain Res ; 97(2): 194-8, 2001 Dec 30.
Article in English | MEDLINE | ID: mdl-11750077

ABSTRACT

Changes in diazepam binding inhibitor (DBI) mRNA expression after withdrawal from nicotine were examined. Withdrawal from nicotine Increased DBI mRNA expression in cerebral cortices derived from nicotine-dependent mice and in the neurons continuously exposed to nicotine (0.1 microM). These results indicate that withdrawal from nicotine after its long-term exposure induces steep increase of DBI mRNA expression as reported previously in ethanol- and morphine-dependent animals.


Subject(s)
Cerebral Cortex/physiology , Diazepam Binding Inhibitor/metabolism , Substance Withdrawal Syndrome/physiopathology , Tobacco Use Disorder/physiopathology , Animals , Anxiety/physiopathology , Gene Expression/drug effects , Mice , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , RNA, Messenger/metabolism , Receptors, Nicotinic/genetics
7.
J Synchrotron Radiat ; 8(Pt 2): 740-2, 2001 Mar 01.
Article in English | MEDLINE | ID: mdl-11512915

ABSTRACT

X-ray absorption spectra near Ce and Gd K-edges of binary oxide of Ce(x)Gd(1-x)O(3+x)/2 (0 < or = x < or = 0.5) in C-type structure solid solution were measured by use of the beamline BL01B1 at SPring-8. Interatomic distances between rare-earth and oxygen atoms. R(Gd-O) and R(Ce-O), were evaluated with the extended x-ray absorption fine structure analysis and found to increase with x. R(Gd-O) was larger than R(Ce-O) by about 0.1 A. Metal-oxygen distances estimated as their linear combinations, xR(Ce-O) + (1-x)R(Gd-O), well agreed with those determined by X-ray diffraction.

8.
J Biomed Mater Res ; 57(3): 366-73, 2001 Dec 05.
Article in English | MEDLINE | ID: mdl-11523031

ABSTRACT

Adherence of cells to a surface, such as a biomaterial surface, can be significantly influenced by the surface charge on that material. The applicability of electrically charged hydroxyapatite ceramics to selective cell adhesion was examined, and we show that polarized hydroxyapatite has significant effects on cell growth and adhesion. The surface charge applied to polarized hydroxyapatite promotes (i) enhanced colony formation of osteoblast-like cells, (ii) activation of gap junctions, and (iii) specific orienting of neuroblastoma cells. These findings will be of great utility and have significance in applications of tissue engineering, for example, in potential treatments for osteoporosis.


Subject(s)
Durapatite/chemistry , Cell Adhesion , Cell Division , Ceramics , Cytological Techniques , Electrochemistry , Fibroblasts , Humans , Microscopy, Electron, Scanning , Microscopy, Phase-Contrast , Neuroblastoma , Osteoblasts , Surface Properties , Tumor Cells, Cultured
9.
Brain Res Mol Brain Res ; 92(1-2): 12-8, 2001 Aug 15.
Article in English | MEDLINE | ID: mdl-11483237

ABSTRACT

In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.


Subject(s)
Calcium Channel Blockers/pharmacology , Calcium Channels, L-Type/drug effects , Calcium Signaling/drug effects , Calcium/metabolism , Cerebral Cortex/cytology , Hydroxyl Radical/pharmacology , Nerve Tissue Proteins/drug effects , Neurons/drug effects , Thiourea/analogs & derivatives , 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Animals , Calcium Channels/classification , Calcium Channels/drug effects , Calcium Channels, L-Type/metabolism , Cells, Cultured/drug effects , Cerebral Cortex/metabolism , Deferoxamine/pharmacology , Ferrous Compounds/pharmacology , Free Radical Scavengers/pharmacology , Hydrogen Peroxide/pharmacology , Ion Channel Gating , Ion Transport/drug effects , Iron Chelating Agents/pharmacology , Mannitol/pharmacology , Mice , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Nifedipine/pharmacology , Potassium Chloride/pharmacology , Thiourea/pharmacology , omega-Agatoxin IVA/pharmacology , omega-Conotoxin GVIA/pharmacology
10.
Int J Pharm ; 224(1-2): 105-14, 2001 Aug 14.
Article in English | MEDLINE | ID: mdl-11472819

ABSTRACT

The bioavailability of elcatonin (ECT) via the nasal route was investigated with a powder dosage form utilizing water-insoluble calcium carbonate (CaCO(3)) in comparison with the liquid dosage form. Total radioactivity and the radioactivity of intact [3H]ECT were measured to evaluate the nasal absorption in vivo and the nasal mucosal transport in vitro. The systemic bioavailability of both total radioactivity and intact [3H]ECT following intranasal administration of the powder formulation in rats was significantly greater than in the case of the liquid formulation. In contrast, similar permeability of ECT across excised rabbit nasal mucosa was seen for both formulations, and was close to that of [14C]inulin, suggesting that the ECT transport is predominantly paracellular in each case. However, the powder formulation significantly prolonged the residence time of [3H]ECT in the rat nasal cavity, compared with the liquid formulation. We conclude that the powder formulation utilizing CaCO(3) improves the nasal bioavailability by increasing the residence time of ECT in the nasal cavity and is likely to be effective in increasing systemic drug delivery.


Subject(s)
Administration, Intranasal , Calcitonin/analogs & derivatives , Calcitonin/pharmacokinetics , Animals , Area Under Curve , Biological Availability , Calcitonin/administration & dosage , Calcium/blood , Calcium Carbonate/administration & dosage , Calcium Carbonate/pharmacokinetics , Female , Humans , In Vitro Techniques , Male , Nasal Mucosa/metabolism , Permeability , Powders , Rabbits , Rats , Rats, Wistar , Tritium/chemistry
11.
Alcohol Clin Exp Res ; 25(5 Suppl ISBRA): 189S-196S, 2001 May.
Article in English | MEDLINE | ID: mdl-11391070

ABSTRACT

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hiroshi Suwaki and Harold Kalant. The presentations were (1) Influence of ADH genotypes on acute alcohol withdrawal syndrome in Japanese, by Susumu Higuchi; (2) Use of genetic analyses to refine phenotypes related to alcohol tolerance and dependence, by John C. Crabbe; (3) Neurochemical basis for alcohol dependence, by Seitaro Ohkuma and Masashi Katsura; (4) Adenylyl cyclase and development of tolerance to addictive drugs, by Masami Yoshimura; (5) Tolerance in rat lines selectively bred for alcohol preference, by Robert C. Stewart and Ting-Kai Li; and (6) Ethanol reinforcement, dependence, and vulnerability to relapse: Interactions between neuroadaptive and conditioning factors, by Friedbert Weiss.


Subject(s)
Alcoholism/genetics , Aldehyde Dehydrogenase/genetics , Drug Tolerance/genetics , Reinforcement, Psychology , Substance Withdrawal Syndrome/genetics , Alcohol Dehydrogenase/genetics , Aldehyde Dehydrogenase, Mitochondrial , Animals , Conditioning, Psychological/physiology , Genotype , Humans , Mice , Phenotype , Research , Risk Factors , Secondary Prevention
12.
Nihon Yakurigaku Zasshi ; 117(3): 159-68, 2001 Mar.
Article in Japanese | MEDLINE | ID: mdl-11288485

ABSTRACT

Mechanisms for formation of drug dependence and emergence of withdrawal syndrome are not yet fully understood despite of a huge accumulation of experimental and clinical data. Several clinical features of withdrawal syndrome are considered to be common (i.e., anxiety) among patients with drug dependence induced by different drugs of abuse. In this review, we have discussed the possibility of the functional involvement of diazepam binding inhibitor (DBI), an endogenous neuropeptide for benzodiazepine receptors with endogenously anxiogenic potential, in the development of drug dependence and emergence of its withdrawal symptom. The levels of DBI protein and its mRNA significantly increased in the brain derived from mice dependent on alcohol (ethanol), nicotine and morphine, and abrupt cessation of these drugs facilitated further increase in DBI expression. In the cases of nicotine- and morphine-dependent mice, concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase in DBI expression. Therefore, these alterations in DBI expression have a close relationship with formation of drug dependence and/or emergence of withdrawal syndrome and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse.


Subject(s)
Brain/metabolism , Carrier Proteins , Substance-Related Disorders , Animals , Carrier Proteins/metabolism , Carrier Proteins/physiology , Diazepam Binding Inhibitor , Ethanol , Humans , Morphine , Nicotine , Substance Withdrawal Syndrome/etiology , Substance-Related Disorders/etiology
13.
Brain Res Mol Brain Res ; 88(1-2): 161-5, 2001 Mar 31.
Article in English | MEDLINE | ID: mdl-11295242

ABSTRACT

Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and its mRNA expression in mouse cerebral cortical neurons were examined. A significant increase in DBI mRNA expression was observed 1 day after the exposure to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure, whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no changes in the expression. Similarly, no changes in the expression were found by the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover, neuronal DBI content significantly increased by treatment with NMDA, which was completely abolished by MK-801. These results indicate that continuous activation of NMDA receptors is an essential factor for increasing DBI expression in the neurons.


Subject(s)
Carrier Proteins/genetics , Carrier Proteins/metabolism , Cerebral Cortex/cytology , Neurons/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Diazepam Binding Inhibitor , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Gene Expression/drug effects , Gene Expression/physiology , Mice , N-Methylaspartate/pharmacology , Neurons/drug effects , RNA, Messenger/analysis
14.
Life Sci ; 68(11): 1215-22, 2001 Feb 02.
Article in English | MEDLINE | ID: mdl-11233989

ABSTRACT

Mechanisms for formation of drug dependence and expression of withdrawal syndrome have not fully clarified despite of huge accumulation of experimental and clinical data at present. Several clinical features of withdrawal syndrome are considered to be common among patients with drug dependence induced by different drugs of abuse. One of them is anxiety. Recent investigations have revealed that diazepam binding inhibitor (DBI), a peptide consisting of 87 amino acids with molecular weight of about 10 kDa, serves as an inverse agonist for benzodiazepine (BZD) receptors with endogenously anxiogenic potential. These lines of data suggest that cerebral DBI expression in brain may participates in formation of drug dependence and/or emergence of withdrawal syndrome. Based on this working hypothesis, we have examined DBI expression in the brain derived from mice depended on alcohol (ethanol), nicotine, and morphine to investigate functional relationship between cerebral DBI expression and drug dependence. Cerebral DBI expression significantly increases in animals with drug dependence induced by these drugs, and in the cases of nicotine- and morphine-dependent mice concomitant administration of antagonists for nicotinic acetylcholine and opioid receptors, respectively, abolished the increase. Abrupt cessation of administration of drugs facilitated further increase in DBI expression. Therefore, these alterations in DBI expression have close relationship with formation of drug dependence and/or emergence of withdrawal syndrome, and are considered to be a common biochemical process in drug dependence induced by different drugs of abuse. Finding and elucidation of mechanisms for common biochemical alterations among drug dependence may provide a clue to clarify mechanisms for formation of drug dependence and/or emergence of withdrawal syndrome.


Subject(s)
Brain/metabolism , Carrier Proteins/metabolism , Substance-Related Disorders/metabolism , Alcoholism/metabolism , Animals , Brain Chemistry , Carrier Proteins/analysis , Diazepam Binding Inhibitor , Ethanol/administration & dosage , Humans , Mice , Morphine/administration & dosage , Morphine Dependence/metabolism , Nicotine/administration & dosage , Substance Withdrawal Syndrome/metabolism , Tobacco Use Disorder/metabolism
15.
Prog Neurobiol ; 64(1): 97-108, 2001 May.
Article in English | MEDLINE | ID: mdl-11250064

ABSTRACT

This review summarizes the stimulatory potentials of NO and peroxynitrite (OONO-) on neurotransmitter release in the central nervous system. Exogenous and endogenous NO stimulates to release neurotransmitter. NO synthesized intracellularly diffuses out through neuronal membrane and acts on the outer side of membrane to depolarize neuronal membrane, which triggers neurotransmitter release. NO-induced release of neurotransmitters is mediated by Ca2+-dependent and -independent processes. The latter process is operated by reverse process of the Na+-dependent carrier-mediated neurotransmitter uptake system or by unknown mechanisms. Ca2+-dependent release of neurotransmitter occurs in part subsequent to increase in Ca2+ influx via VDCCs, although N-type VDCCs may not involve in this action of NO because of suppression of Ca2+ influx through N-type VDCCs by NO. Participation of cGMP formation by NO on neurotransmitter release is controversial. A superoxide scavenger, Ca2+, Zn(2+)-superoxide dismutase, abolishes NO-induced neurotransmitter release and synthesized OONO- induces neurotransmitter release, indicating that OONO- participates in NO-evoked neurotransmitter release.


Subject(s)
Central Nervous System/metabolism , Neurotransmitter Agents/metabolism , Nitrates/metabolism , Nitric Oxide/metabolism , Synapses/metabolism , Synaptic Transmission/physiology , Animals , Humans
16.
J Neurochem ; 76(2): 341-50, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11208897

ABSTRACT

The effect of peroxynitrite (OONO-) on voltage-dependent Ca2+ channels (VDCCs) was examined by measuring [45Ca2+] influx into mouse cerebral cortical neurones. OONO- time- and dose-dependently increased [45Ca2+] influx and this increase was abolished by manganese (III) tetrakis (4-benzoic acid) porphyrin, a scavenger for OONO-. Inhibition of cyclic GMP (cGMP) formation did not alter the OONO(-)-induced [45Ca2+] influx. OONO-, as well as 30 mm KCl, significantly increased fluorescence intensity of cell-associated bis-(1,3-dibutylbarbituric acid) trimethine oxonol (bis-oxonol). Tetrodotoxin and membrane stabilizers such as lidocaine dose-dependently suppressed OONO(-)-induced [45Ca2+] influx. Although each of 1 microM nifedipine and 1 microM omega-agatoxin VIA (omega-ATX) significantly inhibited the OONO(-)-induced [45Ca2+] influx and the concomitant presence of these agents completely abolished the influx, 1 microM omega-conotoxin GVIA (omega-CTX) showed no effect on the influx. On the other hand, OONO- itself reduced 30 mM KCl-induced [45Ca2+] influx to the level of [45Ca2+] influx induced by OONO- alone, and the magnitude of this reduction was as same as that of KCl-induced [45Ca2+] influx by omega-CTX. These results indicate that OONO- increases [45Ca2+] influx into the neurones through opening P/Q- and L-type VDCCs subsequent to depolarization, and inhibits the influx through N-type VDCCs.


Subject(s)
Calcium Channels/metabolism , Calcium/metabolism , Ion Transport/drug effects , Neurons/metabolism , Peroxynitrous Acid/pharmacology , Anesthetics, Local/pharmacology , Animals , Calcium Channel Blockers/pharmacology , Calcium Radioisotopes , Cells, Cultured , Cyclic GMP/biosynthesis , Dose-Response Relationship, Drug , Fluorescent Dyes , Free Radical Scavengers/pharmacology , Ion Transport/physiology , Mice , Mice, Inbred Strains , Neurons/cytology , Neurons/drug effects , Potassium Chloride/pharmacology , Tetrodotoxin/pharmacology , Thiobarbiturates
17.
Brain Res Mol Brain Res ; 80(2): 132-41, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-11038246

ABSTRACT

We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.


Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Calcium Channels, L-Type/metabolism , Carrier Proteins/genetics , Neurons/enzymology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Anesthetics, Local/pharmacology , Animals , Binding, Competitive/physiology , Calcium Channel Blockers/pharmacology , Calcium Radioisotopes/pharmacokinetics , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cells, Cultured , Cerebral Cortex/cytology , Diazepam Binding Inhibitor , Dibucaine/pharmacology , Enzyme Inhibitors/pharmacology , Gene Expression/drug effects , Gene Expression/physiology , Hexamethonium/pharmacology , Lidocaine/pharmacology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Neurons/chemistry , Neurons/cytology , Nicotine/metabolism , Nicotinic Agonists/metabolism , Nicotinic Antagonists/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Procainamide/pharmacology , RNA, Messenger/metabolism , Sulfonamides/pharmacology , Tetrodotoxin/pharmacology , Tritium , omega-Agatoxin IVA/pharmacology , omega-Conotoxin GVIA/pharmacology
18.
Curr Eye Res ; 20(3): 166-72, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10694890

ABSTRACT

PURPOSE: Transforming growth factor -beta2 (TGF-beta2) is a predominant isoform of TGF-betas in the eye and plasmin is a peptidase with many functions. To better understand the pathogenesis of retinal microcirculation disorders, the effects of TGF-beta2 and plasmin on cultured bovine retinal pericytes were investigated. METHODS: Exogenous TGF-beta2 or plasmin was added to some cultures, DNA synthesis during cell cycle progression was investigated using [(3)H]thymidine incorporation. Anti-TGF-beta2 antibody was added to neutralize the effects of TGF-beta2. TGF-beta2 in the culture medium was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Exogenous TGF-beta2 (10 pg to 100 ng/mL) suppressed DNA synthesis. Pericytes produced TGF-beta2. Anti-TGF-beta2 antibody neutralized TGF-beta2 and accelerated DNA synthesis, which shows that pericytes regulate their own cell cycle by action of the autocrine and/or paracrine system of TGF-beta2. Plasmin (0.2 to 0.5 U/mL) accelerated DNA synthesis in a dose-dependent manner, while addition of aprotinin, a protease inhibitor, counteracted this effect of plasmin. The concentration of TGF-beta2 in the culture medium decreased with the addition of plasmin. Simultaneous addition of both plasmin and anti-TGF-beta2 antibody accelerated DNA synthesis. High and low glucose concentrations of the culture medium did not affect DNA synthesis. CONCLUSIONS: Our results suggest that TGF-beta2 and plasmin respectively decrease and increase DNA synthesis. In a retinal microcirculation disorder, they may play competitive roles in the cell cycle of pericytes.


Subject(s)
Cell Division/drug effects , Fibrinolysin/pharmacology , Pericytes/drug effects , Retina/drug effects , Transforming Growth Factor beta/pharmacology , Animals , Cattle , Cells, Cultured , Culture Media/pharmacology , Culture Media, Conditioned/chemistry , Dose-Response Relationship, Drug , Drug Interactions , Glucose/pharmacology , Pericytes/cytology , Retina/cytology , Thymidine/pharmacokinetics , Time Factors , Transforming Growth Factor beta/metabolism , Tritium
19.
Hum Mutat ; 15(1): 118, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10612840

ABSTRACT

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder of fatty acid oxidation caused by defective cellular carnitine transport. The disease is characterized by metabolic derangement simulating Reye's syndrome, hypoglcaemia, progressive cardiomyopathy and skeletal myopathy. Recently, it was shown that SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5). We report two novel mutations, W283R and V446F, which are both missense mutations in an affected infant. In vitro expression studies demonstrated that both are actually function-loss mutations with virtually no uptake activity. This is the first report of compound heterozygosity for two missense mutations in a patient with SCD. Hum Mutat 15:118, 2000.


Subject(s)
Carnitine/deficiency , Carrier Proteins/genetics , Membrane Proteins/genetics , Organic Cation Transport Proteins , Carnitine/metabolism , Carrier Proteins/metabolism , Cell Line , Heterozygote , Humans , Infant , Male , Membrane Proteins/metabolism , Mutagenesis, Site-Directed , Mutation, Missense , Solute Carrier Family 22 Member 5
20.
Hepatogastroenterology ; 46(26): 1199-201, 1999.
Article in English | MEDLINE | ID: mdl-10370691

ABSTRACT

Patients with von Hippel-Lindau disease (VHLD) may develop pancreatic lesions, including cysts, serous cystadenomas and islet cell tumors. However, only a few cases of pancreatic metastasis have been reported. We present a case of VHLD with multiple pancreatic metastases from renal cell carcinoma. One of the metastases invaded the duodenum, causing massive bleeding.


Subject(s)
Carcinoma, Renal Cell/secondary , Gastrointestinal Hemorrhage/etiology , Kidney Neoplasms/complications , Pancreatic Neoplasms/secondary , von Hippel-Lindau Disease/complications , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Duodenum/pathology , Duodenum/surgery , Female , Gastrointestinal Hemorrhage/pathology , Gastrointestinal Hemorrhage/surgery , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Middle Aged , Neoplasm Invasiveness , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy , von Hippel-Lindau Disease/pathology , von Hippel-Lindau Disease/surgery
SELECTION OF CITATIONS
SEARCH DETAIL
...