[Cholinesterase inhibitor].
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Biomedical subjects
Publications and source records attributed to A Ueki.
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We reported two families each propositus of which exhibited extrapyramidal signs and dementia with bilateral basal ganglia calcifications (BGC), while some of the other non-symptomatic family members showed BCG on brain CT by further examinations. Family 1) A 49-year-old woman was normal until her mid 40s when her memory began to fail. At age 40, dementia, finger-tremor and rigidity were observed and with brain CT and Magnetic Resonance Imaging, BCG and dentate calcifications were found. Her two daughters (20 years old and 26 years old) were free of any neuropsychiatric symptoms, but with CT examinations disclosed BCG. Family 2) A 40-year-old man. His symptoms started at 33 years old. He noticed gradually increasing finger-tremor, rigidity and dysarthria. At 40 years he showed mild dementia and BCG on Brain CT. His mother (64 years old) was non-symptomatic but CT showed that she had BCG. In the two families the calcium, phosphorous and parathyroid hormone levels, and Ellsworth-Howard test were normal. Other specific etiology including infections and somatic abnormalities was not discovered. Familial idiopathic basal ganglia calcification was considered to be rare. But the main purpose of this report is to point out that we must pay attention to the possibility of BCG of non-symptomatic family members if one showed dementia and extrapyramidal signs, and BCG on Brain CT in middle age.
We have found that interleukin 3 (IL-3), a growth factor for hematopoietic cells, is a novel trophic factor for mouse and rat central cholinergic neurons. It enhanced neurite outgrowth and elevated choline acetyltransferase activity. The effect seems to be specific for cholinergic neurons, since somatostatin release and glutamic acid decarboxylase and 2',3'-cyclic nucleotide 3'-phosphodiesterase activities were not significantly influenced by IL-3. In vivo, IL-3 was infused into the lateral ventricles of rats after unilateral axotomy of the septohippocampal pathways. Two weeks later, the IL-3-treated animals showed significant numbers of acetylcholinesterase-positive neurons remaining in the septal region.
Asbestos fibres are known to depress the mitogenic stimuli of phytohaemagglutinin (PHA) to lymphocytes. We examined effects of asbestos (chrysotile) fibre on the proliferation of PHA-stimulated lymphocytes and the PHA binding activity of lymphocytes in vitro. The incorporation of 3H-thymidine and the expression of interleukin-2 receptor were depressed when the cells were exposed to 50 micrograms/ml of chrysotile fibre. The PHA binding activity of lymphocytes was significantly enhanced after chrysotile fibre exposure, as compared with non-exposed group. These results indicate that the depression of PHA stimuli with chrysotile fibre was not due to blocking of PHA binding to lymphocytes. The enhancement of PHA binding activity by chrysotile fibre was observed on CD8+ but not on CD4+ cells. It is possible, therefore, that treatment of peripheral blood mononuclear cells with chrysotile fibre induces increased reactivity of CD8+ cells with PHA, and that intensely activated CD8+ cells suppress proliferation of lymphocytes.
HL-60 cells were derived from a patient with myelocytic leukemia, and are known to be in the promyelocytic stage and to differentiate into myelocytes or granulocytes after induction with several materials, e.g., DMSO, retinoic acid, and interferons. The authors intended in this report to determine whether asbestos fibers have any effect on the differentiation processes of HL-60 cells induced with DMSO. The cells were induced to differentiate by incubation with 1.25% DMSO for 4 days. A decrease in the percentage of c-myc-protein-positive cells and an increase in the number of C3bi receptor (CD11b) positive cells were observed after differentiation. When crocidolite (50 micrograms/ml) was added to the culture dishes at the beginning of the experiments, the differentiation was inhibited. An increase in the percentage of c-myc-protein-positive cells and a decrease in that of C3bi-receptor-positive cells were observed compared with the cells induced with DMSO alone. It has been reported that DMSO activates phospholipid- and Ca2(+)-dependent protein kinase and induces the differentiation of HL-60 cells. The mechanisms of inhibition by crocidolite fibers of the effects of DMSO remain to be clarified, but the strength of activation of phospholipid- and Ca2(+)-dependent protein kinase may play an important role in the following induction of cell differentiation.
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In this study, urinary output of both neutral (tribulin) and basic monoamine oxidase inhibitory activity was measured in parkinsonian patients, other neurological patients and controls. No significant differences in output were found between these different groups. In general, tribulin output rose with age, in parallel with known changes in monoamine oxidase B activity.
The excitotoxin kainic acid (10 nmol/microliter) was used to produce bilateral lesions in the nucleus basalis magnocellularis (NBM) of rats which provides extensive cholinergic innervation to the cerebral cortex. The behavioral effects of physostigmine, 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) were investigated by observing locomotor activity, shock sensitivity and passive avoidance response in the NBM-lesioned rats. Evaluation of locomotor activity and shock sensitivity in the experimental animals did not reveal any sensorimotor disturbances caused by the lesions. Oral administration of 1 and 2 mg/kg physostigmine reduced the locomotor activity in the NBM-lesioned rats, while physostigmine (0.5 mg/kg), THA (1 or 3 mg/kg) and NIK-247 (1 or 3 mg/kg) had no effect on locomotor activity. Compared with the sham-operated controls, the NBM-lesioned rats exhibited a significantly lesser deficit in the retention of the passive avoidance response. THA (1 or 3 mg/kg) and NIK-247 (1 or 3 mg/kg) elicited good retention of the passive avoidance response. Rats with NBM lesions showed impaired acquisition of a passive avoidance response when trained repeatedly at 24-h intervals. Also, when post-training NBM lesions were induced, there was rapid extinction of the acquired passive avoidance response. THA or NIK-247 administered at doses of 3 mg/kg significantly increased response latencies of post-trained NBM-lesioned rats. THA or NIK-247 administered once a day in doses of 1 or 3 mg/kg p.o. produced a very significant increase of acetylcholine in the cerebral cortex of NBM-lesioned rats after the 21st administration. These finding suggest that THA and NIK-247 exert an ameliorating effect on memory disturbance induced by NBM lesions in rats.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), or 0.9% saline, was administered to a group of common marmosets initially treated with the toxin 12-18 months previously. Initial treatment had consisted of a cumulative dose of 6-22 mg/kg (i.p.) which caused marked parkinsonism. Subsequently, the animals gradually recovered normal motor function. Further treatment consisted of a cumulative dose of MPTP of 78-83 mg/kg (i.p.) but this produced only modest akinesia. At 12-18 months after the initial treatment with MPTP, the content of dopamine, HVA and DOPAC in the caudate and putamen was markedly reduced. However, levels of dopamine, HVA and DOPAC in the nucleus accumbens were normal. Three months after the second treatment with MPTP there was no further decrease in the content of dopamine in the caudate-putamen. However, in the nucleus accumbens the content of dopamine, HVA and DOPAC was now reduced. The initial treatment with MPTP substantially decreased the binding of [3H]mazindol in the caudate-putamen but less so in the nucleus accumbens. Only a small additional decrease occurred upon further treatment with MPTP. The density of tyrosine hydroxylase (TH) immunoreactive cells in substantia nigra was reduced after the initial treatment with MPTP. However, the cell loss was far less marked than the decrease in terminal density, assessed by the binding of [3H]mazindol. Subsequent treatment with MPTP caused a small further loss of tyrosine hydroxylase-positive cells. Initial treatment with MPTP may kill the majority of MPTP-sensitive dopamine cells in the nigra. Compensation by the remaining nigrostriatal neurones may account for the behavioural recovery observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Destruction of the anterior one-third of the right saccule in the guinea pig resulted in a marked eye deviation simultaneously towards the ear and downward on the operated side and a marked upward eye deviation on the non-operated side in the standard head position. During head inclination towards the operated side, both eyes showed a disturbed ocular counter-rolling (OCR). The disturbance of OCR was more severe in the eye on the operated side than in the eye on the non-operated side. Brief interpretation about eye position in the standard head position in the regional destructive group showed that the eye ball on the operated side showed a marked deviation simultaneously upward and towards the ear, while the eye ball on the non-operated side showed an upward deviation on the 1st and 3rd days after the operation. OCR after regional destruction was seen as follows: During head inclination towards the operated side, both eyes showed disturbed OCR. The disturbance of OCR was more severe in the eye on the operated side. Most animals in our experiment showed this disturbed OCR which was compensated and normalized by the third postoperative week; relatively shorter (faster) than the total destruction. These results suggest that when the head is inclined around its longer axis, the saccule on the side of head inclination plays a principal role in the otolith-ocular reflex.
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Choline acetyltransferase (CAT) and glutamate decarboxylase (GAD) activities and [3H] quinuclidinyl benzilate ([3H]QNB) binding were determined in the rat frontal cortex following damage to the basal forebrain cholinergic system. Pre- and postsynaptic changes in the cholinergic system with the passage of time were also studied. After a unilateral injection of kainic acid into the right ventral globus pallidus, the GAD levels remained unaffected, but the CAT levels decreased to 63.4% after 7 days. After 12 weeks, the CAT levels had returned to 87% of the control value. The Bmax of [3H]QNB binding for the muscarinic receptor was higher in the ipsilateral cortex up to 4 weeks. On the other hand, the KD value at 12 weeks was higher without a change in the Bmax of the [3H]QNB binding. These findings might indicate an ongoing compensatory receptor mechanism of denervation supersensitivity as a response to early changes in presynaptic cholinergic activity and the production of postsynaptic effect with presynaptic cholinergic damage over a long period of time.
The third component of complement (C3) is synthesized and released by cultured human capillary endothelial cells. After the incubation of cells in a methionine-free medium containing 35S-methionine for 48 hr, culture supernatants were immunoprecipitated with anti-human C3 serum. SDS solubilization and 2-ME reduction of the immunoprecipitates, followed by separation with SDS-polyacrylamide gel electrophoresis and autoradiography, revealed two major bands comparable to those of the alpha and beta chains of human C3. The content of C3 in the culture medium harvested at different time-intervals was determined by ELISA. The C3 secretion rate was about 250 ng/10(6) cells/5 days in the primary culture medium and 75 ng/10(6) cells/5 days after seven passages. The capillary endothelial cells described here have factor VIIIRAg specific for endothelial cells, and exhibit ring formation resembling capillary lumina, but they lack Weibel-Palade bodies.
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Asbestos fibres of chrysotile, crocidolite and amosite were incubated with eight types of human cell lines in vitro. These asbestos fibre were cytotoxic to fibroblasts and monocyte like cells, as is already known. On the other hand, immature B lymphocyte lines (B1 2) were stimulated significantly by chrysotile and crocidolite, while a mature B cell line (B3) was not affected. Cell proliferation of a T cell line and an erythromyeloid cell line also was not affected by asbestos. For the stimulation of lymphocytes, the binding of the mitogen to the reactive sites on the lymphocyte surface is thought to be indispensable. It seems that chrysotile and crocidolite asbestos can bind to immature B lymphocytes, but not to mature B cells.
Postsynaptic potentials evoked by stimulating the substantia nigra (SN) were recorded intracellularly from ipsilateral ventral medial (VM), ventral lateral (VL), and ventral anterior (VA) nuclei of the thalamus in cats anesthetized with sodium pentobarbital. SN stimulation evoked inhibitory postsynaptic potentials (IPSP) at a short latency in VM neurons (mean 1.68 ms, SD 0.23, n = 59). The IPSP were produced monosynaptically because linear regression analysis of latency vs. conduction distance between stimulating and recording sites indicated a synaptic delay of less than 0.6 ms. Conduction velocity for these fibers was calculated to be 4.48 m/s. The spots from which IPSP were produced with the lowest threshold were determined for each of 38 VM neurons. IPSP origins thus determined were distributed in the pars reticulata of the SN (SNr) and in the area where nigro-thalamic fibers run. Neurons which received IPSP from the SNr were distributed in the VM nucleus, ventromedial to the VL nucleus, where fibers from the contralateral brachium conjunctivum terminate. Convergence of nigral and cerebellar impulses was not observed in thalamic neurons sampled in this study. Stimulation of the entopeduncular nucleus (ENT) also produced monosynaptic IPSP in VL-VA neurons. The SNr-related cell group was located ventromedially and caudally to the ENT-related cell group. No convergence of nigral and pallidal influences was observed within thalamic neurons.