Search PubMed⌕ Search

Biomedical subjects

A Ueki

Publications and source records attributed to A Ueki.

At least 109 records · Page 6Linked to original sources

Evidence for a preventive action of the vigilance-promoting drug modafinil against striatal ischemic injury induced by endothelin-1 in the rat.

We have studied the ability of the vigilance-promoting drug modafinil to counteract the ischemic lesion produced by a unilateral microinjection of endothelin-1 (ET-1) in the neostriatum of the rat using a combined morphometrical, biochemical, cardiovascular and behavioral analysis. ET-1 was injected unilaterally into the neostriatum. The ET-1-induced lesion volume, which was determined by a computer-assisted morphometrical analysis, was reduced by the 7-day modafinil treatment (10, 30, and 100 mg/kg i.p.) in a dose-related way. Modafinil also produced a dose-related counteraction of the ET-1-induced increase of perfusate lactate levels, as determined by intrastriatal microdialysis without affecting the ET-1 induced reduction of striatal blood flow, as determined by laser-Doppler flowmetry. The ipsilateral rotational behavior induced by apomorphine in the ET-1-lesioned rats was reduced dose-dependently by modafinil treatment. Thus, morphological, neurochemical, and behavioral evidence that the putative ischemic striatal injury induced by microinjection of ET-1 in the rat neostriatum is counteracted in a dose-dependent way by modafinil treatment has been obtained. The mechanism does not appear to involve an increase in striatal blood flow. It is instead speculated that its powerful preventive action in striatal ischemic injury may be related to a reduced anaerobic metabolism.

Amphetamine↗

Nucleic acids induce the formation of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a model system.

Effects of nucleic acids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were studied in a model system. When a mixture of a certain amount of DNA or RNA, creatinine (1 mmol) and phenylalanine (1 mmol) in 10 ml of 50 mM phosphate buffer, pH 7.4, was heated at 60 degrees C for 4 weeks in a screw-capped vial, PhIP was produced, and the yield of PhIP was dependent on the heating time as well as the dose of nucleic acid added to the mixture. However, PhIP was not detectable in the mixtures without the presence of nucleic acids. Both deoxyribonucleotides and ribonucleotides tested induced the formation of PhIP under the presence of phenylalanine and creatinine, although bases of nucleic acids such as adenine and guanine did not induce PhIP formation. Moreover, we confirmed that 2-deoxy-D-ribose as well as D-ribose induced the formation of PhIP in the presence of creatinine and phenylalanine. These results indicate that nucleic acids can induce the formation of PhIP in the presence of creatinine and phenylalanine in the model system. Our data also suggest that pentose in nucleic acids may participate in PhIP forming reactions.

Carcinogens↗

[Effect of shampoo on human hair cystatin extraction].

It is known that cystatins have not only regulatory functions in cellular protein catabolism, but also other physiological functions against viral and/or bacterial infection. Recently we have fond cystatin in the human hair shaft. The activity of human hair cystatin in a water extract of pieces of it reached a plateau after 3-hour incubation. The activity of cystatin was compared among three different lengths of hair. The shorter the hair was cut, the more hair cystatin was extracted. Cystatin was more easily extracted by adding a water-soluble detergent. On the basis of these results, the loss of human hair cystatin from the hair shaft seemed to be affected by the condition of the hair surface and by the detergents in hair shampoo.

Cystatins↗

[Acute progressive polyneuropathy in a patient with Waldenström macroglobulinemia].

A case of Waldenström's macroglobulinemia (WM) (IgM-kappa type) associated with acute-onset demyelinating peripheral neuropathy is reported. A 49-year-old woman was admitted to our hospital because of general fatigue and recurrent syncope attacks. She was treated with vincristine, cyclophosphamide, epirubicin and prednisolone. By 10th hospital day, her clinical condition improved and serum viscosity was reduced. However, on the 21st hospital day, she suffered from rapidly progressive writing and gait disturbance. Neurological examination showed muscular atrophy and weakness in the distal part of four extremities. Deep tendon reflexes were diminished. There was no sensory deficit. Cerebrospinal fluid was normal. Anti-myelin associated glycoprotein activity of her serum was negative. Both motor and sensory nerve conduction velocities were markedly decreased. Biopsy of sural nerve revealed marked demyelination and onion bulb formation. There was IgM deposition on myelin sheath. Minimal axonal changes excluded the possibility of vincristine neuropathy. Plasmapheresis improved her symptoms, but nerve conduction velocities remained unchanged. Polyneuropathy associated with WM is usually gradual onset and sensory dominant. In this case, associated neuropathy was acute onset, progressive and motor dominant. This type of neuropathy in patients with WM is very rare.

Acute Disease↗

[Leptomeningeal abnormality on Gd-DTPA enhanced MRI in a case of SLE presenting diffuse organic brain syndrome].

Involvement of the central nervous system associated with SLE (CNS lupus) is not rare. Two types of CNS lupus are noted clinically; one group manifesting focal neurological symptoms and another group showing mental symptoms. Though it is well known that neurological symptoms are caused by arteritis and thrombus, pathophysiological mechanisms leading to mental symptoms remain obscure and there is no established clinical evidence responsible for these symptoms. A 41-year-old woman was confused and her attention was markedly impaired. Her mental symptoms consisted of disorientation, restlessness, euphoria and emotional incontinence. There were neither focal neurological signs nor meningeal signs. Cerebrospinal fluid (CSF) examination showed increased number of polymorphonuclear cells and permeability of the blood-brain barrier, calculated based on the CSF/plasma protein ratio, was also elevated. Repeated bacteriological examinations revealed to be negative. Gd-DTPA MRI demonstrated diffuse enhancement of the cerebral leptomeninges. Methylprednisolone pulse therapy ameliorated her mental deterioration effectively, and subsequently the leptomeningeal enhancement with Gd-DTPA MRI disappeared in parallel. These radiological and laboratory findings suggest that SLE itself causes inflammation of vessels in the leptomeninges and adjacent cerebral cortex. We consider mental symptoms associated with SLE may be caused, at least in part, by this mechanism. To our knowledge, we could not find similar reports in the literature. Gd-DTPA enhanced MRI seems to be of clinical use for making diagnosis, evaluating clinical activity and understanding of CNS lupus.

Adult↗

Combined action of paraquat and superoxide on the peroxidation of detergent-dispersed linolenic acid.

We investigated the peroxidative effect of paraquat and active oxygens on detergent-dispersed linolenic acid in phosphate buffer (pH 7.5) from the malondialdehyde (MDA) level. Our complete system and further inclusion of catalase were effective in stimulating MDA formation. On the other hand, xanthine oxidase (XOD) or paraquat omission, superoxide dismutase (SOD) inclusion or anaerobic incubation inhibited the formation of MDA. Ferrous ion was weakly associated with phosphate of the buffer, forming a complex, and the release of ferrous ion from the complex intensified the MDA levels with the complete and catalase inclusion systems. The electron paramagnetic resonance (EPR) spectra using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed that superoxide, produced immediately after the addition of XOD, played a crucial role. We could obtain a DMPO-OOH signal at the starting stage whenever MDA stimulation was observed. The omission of paraquat, however, produced no increase in MDA level in spite of an appearance of DMPO-OOH signal, indicating that paraquat also plays an important role. On the other hand, Desferal, a ferric chelator, showed a concentration-dependent inhibition effect. There was an immediate strong intensity of DMPO-OOH and paraquat signals. We did not, however, observe MDA stimulation at 250 microM Desferal, which confirms that ferrous ion plays an essential role in the lipid peroxidation. These results indicate a combined action of paraquat (or its radical) and superoxide on the accessibility of ferrous ion, including its release from the complex with phosphate, which may be an endogenous chelator. The possibility of ternary complex participation is also discussed.

Cyclic N-Oxides↗

Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro.

Chrysotile asbestos stimulates T lymphocyte subsets. Cell surface CD4 or CD45RA expression in peripheral blood mononuclear cells (PBMC) was downregulated after incubation with chrysotile asbestos in vitro temporarily. The percentage of CD4+CD45RA+ cells and mean fluorescence intensity in CD4 or CD45RA decreased after incubation with asbestos and returned to the original level after 24 h of incubation, which suggests that chrysotile asbestos activates CD4+CD45RA+ cells. No change was observed in CD29 expression. An increased percentage of IL-2R positive cells and an elevated intracellular Ca++ level were also indicative of the activation of PBMC by chrysotile asbestos.

Antigens, CD↗

Crocidolite asbestos suppresses the differentiation of HL-60 cells induced by DMSO.

This study was undertaken to determine if the biological function of inducers for cell differentiation is affected by asbestos fibers, which are sometimes deposited in human tissues. Protein kinase C activity, c-myc protein expression and cell surface CR3 expression were used as the markers of cell differentiation. The function of dimethylsulfoxide (DMSO), an inducer of cell differentiation, was suppressed by the co-culturing of crocidolite asbestos, because DMSO reacted with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effect of crocidolite, reacting rapidly with .O2- before the secondary release of .OH. Asbestos fibers deposited in tissues may inhibit the function of inducers which stimulate immature cells to differentiate, because such inducers frequently are also radical scavengers.

Asbestos↗

Purification and characterization of a cystatin-type cysteine proteinase inhibitor in the human hair shaft.

We found a cysteine proteinase inhibitor in human hair shaft extract treated with 0.01 M Tris HCl buffer, pH 8.0. A yield of 0.2 mg of purified cysteine proteinase inhibitor was obtained from 86 g of hair shaft. The cysteine proteinase inhibitor had a molecular mass of 13 kDa as determined by high-performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was more stable to heat and pH than most proteins and had a pI of 4.7. Immunologically, its antigenicity was the same as that of cystatin A, but differed from that of cystatin B and C, and kininogen. The amino-acid sequence of the first 30 residues from the NH terminus of the inhibitor was identical to that of cystatin A from human epidermis. Hair shaft cysteine proteinase inhibitor is thus considered to be identical to epidermal cystatin A.

Cystatins↗

Candida albicans produces a cystatin-type cysteine proteinase inhibitor.

A cysteine proteinase inhibitor was found in culture media of Candida albicans. Purification to homogeneity of the inhibitor was performed by carboxymethyl-papain-Sepharose affinity, DE-52 ion-exchange, and reverse-phase high performance liquid chromatographies. The purified inhibitor had an M(r) of 15 kDa and a pI of 4.9. It was more stable to heat and pH than most proteins. The N-terminal sequence of the first 30 residues demonstrated high similarity with that of human cystatin A. Thus, C. albicans cysteine proteinase inhibitor seems to belong to the cystatin superfamily. The inhibitor activity of the yeast cellular form was 4.0 times higher than that of the hyphal cellular form in 7-day culture media. It is suggested that the inhibitor has regulatory functions similar to those of its counterpart proteinases in the invasion of host cells.

Candida albicans↗

[Effect of crocidolite fibers on the cathepsin B-like enzyme activity in HL-60 cells].

In a previous study, we found that crocidolite (an asbestos fiber) had an inhibitory effect on the differentiation process of HL-60 cells induced by dimethyl sulfoxide (DMSO). Here we describe the cathepsin B-like enzyme HL-60 cells and the changes of its activity during cell differentiation with or without crocidolite treatment. The cathepsin B-like enzyme in HL-60 cell extracts had almost the same characteristics and the already known cathepsin B as for the pH optima and the effects of proteinase inhibitors. The cathepsin B-like enzyme activity increased according to the cell differentiation induced by DMSO, however, its activity was depressed by crocidolite treatment.

Asbestos↗

Characterization of a cathepsin-H-like enzyme from a human melanoma cell line.

A cathepsin-H-like enzyme has been isolated from cultured human melanoma cells (G 361 cell line). The enzyme is similar to cathepsin H(s) of normal tissues in molecular weight, enzymatic characteristics (substrates, inhibitors, pH optima, Km values), and immunoreactivity. The inactive form of the enzyme with a molecular mass of 40 kDa has been found in the culture medium. The inactive enzyme is activated by acid pH, pepsin, and cathepsin-D-like enzyme treatments and converted into a form with a molecular mass of 28 kDa. The activated extracellular cathepsin-H-like enzyme and the active intracellular enzyme exhibit the same characteristics. The melanoma-derived cathepsin-H-like enzyme degrade fibrinogen and fibronectin, but not laminin or type-IV collagen. We conclude that the extracellular cathepsin-H-like enzyme may have important functions, together with other proteinases, in the destruction of extracellular matrix components, thus enabling proliferation, migration, and metastasis to occur.

Blotting, Western↗

Reversal of learning impairment in ventral globus pallidus-lesioned rats by combination of continuous intracerebroventricular choline infusion and oral cholinergic drug administration.

The effects of separate or combined oral administration of THA (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) and NIK-247 (9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b] quinoline monohydrate hydrochloride) and intracerebroventricular choline infusion using an osmotic minipump were investigated by observing locomotor activity, shock sensitivity, passive avoidance response and cerebral choline and acetylcholine contents in the bilateral ventral globus pallidus-lesioned rat. Evaluation of locomotor activity and shock sensitivity revealed no sensorimotor disturbances caused by combined administration. Intracerebroventricular choline infusion (100 mumol/day) and oral THA or NIK-247 administration (0.5 mg/kg) had no effect on the acquisition of the passive avoidance response, while the combination of oral THA or NIK-247 administration (0.5 mg/kg) and intracerebroventricular choline infusion (100 mumol/day) elicited good acquisition of passive avoidance learning and produced a significant increase of choline and acetylcholine in the cerebral cortex of the bilateral ventral globus pallidus-lesioned rat. These findings suggest that continuous intracerebroventricular choline infusion may intensify the ameliorating effect of THA or NIK-247 on learning disturbance.

Acetylcholine↗

[Effects of asbestos on the cell cycle of PHA-stimulated human peripheral blood lymphocytes].

It is well known that persons exposed to asbestos display systemic immunological alterations: impaired lymphocyte response to PHA, the appearance of autoantibodies and elevation of the serum immunoglobulin level. The authors intend in this report to determine whether asbestos fibres (crocidolite, chrysotile and amosite) have any effect on the cell cycle of human lymphocytes after PHA stimulation. Peripheral blood mononuclear (PBM) cells were incubated with 10 micrograms/ml PHA for 2 days. After PHA stimulation, a decrease in the percentage of cells in the G0 phase and an increase in that of cells in the G1A, G1B and S phases was observed. When asbestos fibres or titanium dioxide (TiO2) was added to the culture dish at the beginning of the experiment, the progression of the cell cycle was inhibited only by asbestos fibres, in which case the percentage of cells in the G0 phase was significantly increased, while those of cells in the G1B and S phases were significantly decreased. The experiment for determining the critical period for inhibition of blastogenic response revealed that no inhibition was demonstrable when crocidolite fibre was added at 24 hr after PHA stimulation. Although the mechanisms of asbestos-fibre-mediated suppression remain to be clarified, these results showed that asbestos fibres act at an early stage (G0 phase) of the cell cycle and suppress the PHA stimulation of PBM cells.

Asbestos↗

[The effects of asbestos fibers on the protein kinase C activity in HL-60 cells. The role of free radicals].

It was confirmed that the function of DMSO as an inducer of cell differentiation was suppressed by co-culture of crocidolite asbestos, using the activity of protein kinase C as indicator, because DMSO reacted with .OH radical released by stimulation with crocidolite and wasted itself. SOD inhibited the effect of crocidolite, because SOD reacted with .O2- released by stimulation with crocidolite and inhibited the subsequent development of .OH.

Asbestos↗

[Hyperkinésie volitionnelle following head injury].

A 13-year-old girl was struck by a car while riding her bicycle. She was comatose on her arrival at the hospital. Neurological examination revealed no focal sign except for right oculo-motor palsy. She became alert 15 days after the head injury when she first experienced a coarse tremor-like movement on the right arm. Neurological examination showed persistent oculo-motor palsy on the right side, decreased sensation of pain and touch on the left. There was no pyramidal deficit. Her gait and speech were normal and joint sensation was intact. A coarse tremor of the right arm was induced by volitional movements especially such as maintaining the arm in certain posture. It was not present at rest. Trajectory of finger-to-nose test was fairly well. However, the tremor became worse when the patient kept her finger near the target. Occasionally myoclonic-jerk and movement oppositionniste were mixed. Superficial EMG recordings of the tremor revealed 4 c/s rhythmic reciprocal grouping discharges, alternating flexor and extensor muscles. From these features, the abnormal movement should better be called tremor type of hyperkinésie volitionnelle (HV). The HV subsided spontaneously 4 months later. MRI of T2-weighted image showed high-intensity areas corresponding anatomically to the caudal part of right red nucleus and the right superior cerebellar peduncle just before its decussation. It is widely believed that lesions in cerebellar outflow pathway (i.e. dentate, red nucleus and thalamus) can cause HV.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗