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Biomedical subjects

A Ueki

Publications and source records attributed to A Ueki.

At least 73 records · Page 4Linked to original sources

Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro.

Silica and related substances such as silicate have been proven to possess "adjuvant effects". We have previously reported a finding of polyclonal human T cell activation induced by silicate as a superantigen in vitro. In this study, we observed activation-induced cell death in human lymphocytes after stimulation with chrysotile, a kind of silicate. Apoptotic cells were detected flow cytometrically using the TUNEL assay, and the maximum appearance of TUNEL positive cells occurred on day 4 of incubation. Simultaneously the manifestation of small-sized cells in the specimens increased implying apoptosis. Fas expression on lymphocytes increased to day 3 of incubation with chrysotile, and then spontaneously decreased on day 4 when remarkable apoptosis could be detected. Based on these results it is conceivable that activation-induced cell death occurred through Fas-Fas ligand interaction in lymphocytes after stimulation with silicate in a concentration with which no acute cytotoxicity has been detected. Whether and how the repeated apoptosis in definite clones of lymphocytes causes the induction of sFas synthesis need clarification.

Asbestos, Serpentine↗

Synapse alteration in hippocampal CA3 field following entorhinal cortex lesion.

To model one aspect of the neurodegeneration observed in Alzheimer's disease and to investigate the synaptic alteration of the hippocampus associated with entorhinal cortex lesion, ibotenic acid was used to produce selective unilateral neuronal loss in rat entorhinal cortex. Immunohistological and microdensitometrical analyses confirmed ibotenic acid lesion of the entorhinal cortex after 3 months and showed a decrease of synaptophysin-immunoreactive substances in the stratum lucidum of the CA3 field. This study demonstrates that entorhinal cortex lesion can lead to synaptic alterations and cause damage to presynaptic terminals with projecting area in the disruption of the entorhinal cortex hippocampus relay passage.

Alzheimer Disease↗

TNF-alpha stimulates the biosynthesis of complement C3 and factor B by human umbilical cord vein endothelial cells.

The human umbilical cord vein (HUVEC) endothelial cells synthesize and secrete complement components. We analyzed the regulation of biosynthesis of the third component of complement (C3) and factor B (Bf) by cytokines in endothelial cells. Production of C3 increased after stimulation with TNF-alpha or IL-1beta and that of Bf with TNF-alpha, TNF-beta and IFN-gamma. TNF-alpha was the most effective in stimulating the secretion of C3 and Bf or the expression of mRNA of C3 or Bf. Preincubation with TNF-alpha for at least 36 or 24 h was needed for the stimulation, respectively. TNF-alpha, together with IFN-gamma had synergistic effects and the release of C3 or Bf increased to about 40- and 26-fold higher than those in control cells after incubation with both cytokines.

Cell Line↗

Determination of isatin in urine and plasma by high-performance liquid chromatography.

A method for the detection and determination of isatin (indole-2,3-dione) in urine and plasma by high-performance liquid chromatography has been developed. It consists of a two-step purification using two different columns with UV detection. With this method, we have reconfirmed that isatin is present in human urine. We have also demonstrated that isatin is present in human plasma and that the isatin levels in spot urine samples reflect the plasma isatin levels. In the present report we describe a rapid and sensitive means of determining urine and plasma isatin for laboratories equipped with a high-performance liquid chromatography system.

Adult↗

High and low activity alleles of catechol-O-methyltransferase gene: ethnic difference and possible association with Parkinson's disease.

Catechol-O-methyltransferase (COMT) is an enzyme that inactivates catecholamines such as adrenaline, noradrenaline, dopamine, and levodopa. Recently an amino acid change (Val-108-Met) of the COMT protein was found to determine high and low activity alleles of the COMT gene. We genotyped 109 Japanese patients with Parkinson's disease (PD) and 153 controls by using polymerase chain reaction (PCR) amplification and digestion by the restriction enzyme NlaIII. The frequency of low activity allele in the controls was 0.29, which was significantly different from that reported in Caucasians (0.50). When comparison was made between patients with PD and controls, homozygosity for the low activity allele was significantly more common among the patients than among the controls (P = 0.017; odds ratio, 2.8, 95% CI 1.2-6.5), suggesting that homozygosity for the low activity allele may increase susceptibility to PD.

Adult↗

Motor neurons in human and rat spinal cord synthesize fibroblast growth factor-9.

Fibroblast growth factor (FGF)-9, initially referred to as a glia-activating factor, is a recently identified member of the FGF family. In the present study we demonstrated that spinal cord motor neurons and dorsal root ganglion neurons were strongly immunostained with specific antibodies to FGF-9 in human and rat tissues. By in situ hybridization using digoxigenin-labeled antisense probe to FGF-9 mRNA, we found specific signals in these neurons in rat. By immunoblotting analysis, we detected a 30/29 kDa doublet band in human spinal cord proteins, which corresponded to the doublet band of originally isolated FGF-9 from culture media. Our results indicate that these neurons synthesize FGF-9.

Animals↗

Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours.

Soluble Fas (sFas) is produced as translation products of alternative mRNA splicing, and antagonizes the membranous Fas molecule in Fas/Fas ligand interactions. We investigated the serum sFas levels in 64 Japanese silicosis patients with no clinical symptoms of autoimmune diseases or malignant tumours, using ELISA for sFas. The serum sFas levels in the silicosis patients were significantly higher than those in healthy volunteers. Elevated serum sFas levels were also detected in patients with systemic lupus erythematosus but, unexpectedly, no difference was observed in sFas levels between progressive systemic sclerosis patients and healthy volunteers. On the other hand, there was no significant difference in the expression of Fas on peripheral blood lymphocytes between the patients with silicosis and age-matched healthy volunteers. These observations provided the first evidence that serum sFas levels are elevated in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. It remains to be clarified whether patients with elevated sFas levels have a tendency to develop autoimmune diseases later, or whether some other distinct factor(s) is necessary to initiate the progression of autoimmune diseases.

Aged↗

[Apolipoprotein E epsilon 4 allel frequencies, plasma alpha 2-macroglobulin and plasminogen activator inhibitor 1 levels in residents of a rural area in Gunma prefecture].

The apolipoprotein E4 (apoE4) epsilon 4 allele is a major riks factor for Alzheimer's disease. However, epsilon 4 is neither a necessary nor a sufficient condition for the development of this disease, and many cognitively healthy elderly people carry the epsilon 4 allele. To look for age-dependent changes in epsilon 4 allele frequencies in the general population, we measured the frequencies in 141 normal healthy residents of a mountainous rural area in north-west Gunma prefecture. Levels of cholesterols in plasma were measured and their relation to apoE genotypes was studied. We also measured the levels of alpha 2-macroglobulin (alpha 2M) and plasminogen activator inhibitor 1 (PAI-1) in blood, and studied their relation to apoE genotypes. Because low-density lipoprotein receptor-related protein (LRP) binds apoE, alpha 2M, and PAI-1, it is of interest to see whether the alpha 2M and PAI-1 concentrations in blood differ between epsilon 4 carriers and non-carriers. ApoE allele frequencies were 0.05, 0.84, and 0.11 for epsilon 2, epsilon 3, and epsilon 4, respectively. In both men and women, the frequency of epsilon 4 was lowest among those in the seventh decade of life. The frequency of epsilon 4 among octagenarians was high (0.17). Serum levels of total cholesterol and low-density lipoprotein cholesterol did not differ significantly between epsilon 4 carriers and non-carriers. The alpha 2M level in serum was higher in women than in men and was higher in older subjects than in younger subjects. Plasma PAI-1 levels were significantly higher in men than in women (Student's t-test, p = 0.0197). Neither alpha 2M levels nor PAI-1 levels differed between epsilon 4 carriers and non-carriers, which suggests that the levels of these two proteins in blood do not reflect the status of LRP in individuals with various apoE genotypes. Studies that include data on life style and diet are necessary before we can conclude that rural life contributes to longevity in epsilon 4 carriers.

Adult↗

[A case of chronic encephalitis due to double infection with herpes simplex and measles viruses].

In a healthy 49-year-old man, a decrease in job efficiency was noticed along with bizarre behavior. On admission, he was euphoric, childish, superficial and had increased libido. Neurological findings were normal. There were no abnormal findings on routine blood tests, hematochemistry or urine analysis. MRI showed no abnormal findings. However, single photon emission CT (SPECT) showed diffuse hypoaccummulation of tracer from the temporal to frontal regions. Lumbar puncture showed clear cerebrospinal fluid (CSF) with pleocytosis and an elevated protein level. Moreover, antibody IgG titers to herpes simplex virus (HSV) and measles virus were elevated, according to EIA [serum HSV -1,202.2x, measles virus 47.1x: CSF HSV-116.1x, measles virus 9.9x]. The ratio of serum to CSF antibody titers of HSV and measles virus were 12.5 and 4.75, respectively. The antibody index values of HSV and measles virus IgG titers were 8.42 and 22.22. The ratio of albumin was 105.7. Chronic, progressive HSV encephalitis is rare, and there have been very few reports of encephalitis due to double infection by HSV and another virus. Our patient was diagnosed as having encephalitis due to double infection with HSV and measles virus, because the ratio of serum to CSF antibody titers was less than 20 and the antibody index values were over 1.91. Moreover, since the IgG index was elevated and the ratio of albumin was not low, it was suggested that the blood-brain-barrier had not been disrupted, and antibodies were being produced chronically in the medullary cavity. Hyperaccummulation of tracer on SPECT studies has been reported in the early stages of HSV encephalitis. In our case, while CT and MRI showed no abnormal findings, SPECT showed diffuse hypoaccummulation. SPECT appears to be a useful tool in the diagnosis of this disorder. In case of chronic, progressive personality change in middle-aged adults, we must be aware of double virus infection of the brain as a possible causal factor.

Antibodies, Viral↗

[A case of rheumatoid pachymeningitis].

Here we present a 53-year-old woman with rheumatoid pachymeningitis. The subject had rheumatoid arthritis (RA) for 15 years. In April, 1996 she began to experience intermittent headaches. In September, her headaches became severe and continuous. In October, she suddenly developed ptosis of the left eye and diplopia. She also started to have dysphagia and she found it increasingly difficult to eat. She was admitted to our hospital on November 1, 1996. Neurological examinations revealed palsies of the left IIIrd, IVth, and VIth, and bilateral IXth, and Xth cranial nerves. Laboratory findings showed leukocytosis, elevated blood sedimentation rate, and positive CRP. Serum RA titer was positive (30x). The cerebrospinal fluid was normal and bacteriological examination was negative. T1-weighted MRI demonstrated hypertrophic cranial dura extending from the falx cerebri to tentorium cerebelli, which was enhanced markedly by Gd-DTPA. The dura adjacent to the cavernous sinus and the clivus were also thickened, which probably caused her cranial polyneuropathies. The dural biopsy showed massive infiltration of the inflammatory cells throughout the dura, proliferation of collagen fibers, and necrotic granuloma with neutrophilic infiltrations. Neither rheumatoid nodules, nor vasculitis were found. Despite the absence of rheumatoid nodules in the dural biopsy, the clinical features, pathologic specimens, and MRI findings of the thickened dura were most consistent with rheumatoid pachymeningitis. Administration of dexamethason ameliorated her headache on the 4th hospital day, and the cranial polyneuropathies completely disappeared on the 35th hospital day. The dural enhancement previously seen on the contrast T1-weighted MRI was diminished. Serum RA titer was also normalized (10x). Rheumatoid pachymeningitis is an extremely rare disease, and only 16 cases were reported in the literatures. Hypertrophic pachymeningitis should be considered as a diagnostic possibility in RA patients who have prolonged headache, and Gd-DTPA MRI is recommended to demonstrate the dural involvement.

Arthritis, Rheumatoid↗

Down regulation of protein kinase C during growth enhancement induced by interleukin-6 on a human myeloma cell line, KMS-11.

Interleukin-6 (IL-6) is one of the most important growth factors for myeloma cells. We examined the effect of recombinant IL-6 on the proliferation of five human myeloma cell lines, which were independently established AT Kawasaki Medical School. Only the KMS-11 cell line among these five lines showed growth enhancement induced by IL-6. Based on the results, a possible contribution of Ca(2+)-phospholipid-dependent protein kinase C (PKC) to the signal transduction in KMS-11 cells during growth enhancement was studied, since PKC may play an important role in malignant transformation or cell proliferation induced by some growth factors, such as IL-6. When exogenous IL-6 was added to KMS-11 culture, we observed (1) reduction of total PKC activity, and (2) translocation of PKC activity from its cytosol fraction to the membrane fraction. These findings may indicate that down regulation of PKC occurred during the myeloma cell proliferation induced by IL-6. However, IL-6 does not appear to be involved in cell proliferation and differentiation in the other cell lines studied.

Cell Division↗

Significantly increased frequency of the apolipoprotein E epsilon 4 allele in elderly non-demented leprosy patients.

Apolipoprotein E (apo E) genotypes in 350 leprosy patients were examined and compared with those of 870 age-matched controls. The allelic frequencies of the apo E gene did not differ between demented patients with leprosy and controls. However, the frequency of apo E epsilon 4 allele was significantly higher in non-demented leprosy patients than in controls (P < 0.001). Of special interest is that the prevalence of E3/4 genotype in non-demented leprosy patients increased significantly with age, being 14.1%, 24.4%, and 28.3% in the 60s, 70s, and 80s, respectively (P < 0.05). These data suggest that apo E epsilon 4 is not a risk factor for senile dementia in elderly leprosy patients, and there exist factors to overcome the risk of apo E4 in leprosy patients.

Age Distribution↗

No association between Parkinson's disease and monoamine oxidase A and B gene polymorphisms.

Parkinson's disease (PD) is thought to be caused by a combination of unknown environmental, genetic and degenerative factors. Among these factors, monoamine oxidase has been considered as a possible factor in the pathophysiology of Parkinson's disease. We have carried out allelic association studies of PD with monoamine oxidase type A (MAOA) and monoamine oxidase type B (MAOB) gene loci using dinucleotide repeat polymorphisms. Distributions of all alleles at MAOA and MAOB gene loci were almost similar in patients and controls. Contrary to previous reports, our findings could not support the hypothesis that susceptibility to PD is associated with MAOA or MAOB polymorphism.

Adult↗

Histological evidence for cholinergic alteration in the hippocampus following entorhinal cortex lesion.

The initial stage of Alzheimer's disease is characterized by neuropathological alteration in the entorhinal cortex. To model one aspect of the neurodegeneration observed and to investigate anatomical changes of the hippocampus associated with unilateral entorhinal cortex lesion, excitotoxin ibotenic acid was used to produce selective unilateral neuronal loss in rat entorhinal cortex. Histological and morphometrical analyses confirmed excitotoxic lesion of the entorhinal cortex after 3 months and showed a decrease of acetylcholineste-rase-stained fibers in the stratum moleculare of the dentate gyrus and the stratum radiatum of the CA3 field. This study demonstrates the importance of the entorhinal cortex in the hippocampal cholinergic function which appears to be important to memory and learning, and raises the possibility that memory deficit in Alzheimer's disease may be associated with partial neuronal loss in the entorhinal cortex.

Acetylcholinesterase↗

Effects of entorhinal cortex lesion on learning behavior and on hippocampus in the rat.

The initial stage of Alzheimer's disease is characterized by a neuropathological change in the entorhinal cortex. In a previous study it was shown that rats with excitotoxic lesion of entorhinal cortex showed an impaired acquisition of passive and active avoidance responses. In this study a rat with excitotoxic lesion of the entorhinal cortex was tested for 'more operant' behavioral learning (i.e., positive reinforcement operant learning). The hippocampus was also examined histologically as acetylcholinesterase-stained sections, and as synaptophysin immunostained sections and examined biochemically by liquid chromatography. Eight weeks after operation, the bilateral entorhinal cortex lesioned rats showed an impaired acquisition of positive reinforcement operant learning. The lesioned side of unilateral entorhinal cortex lesioned rats showed a decrease of acetylcholinesterase-positive fibers in the CA3, the dentate gyrus, and of synaptophysin-positive substances in the CA3. Biochemical study showed a decreased level of acetylcholine in the CA3, and in the dentate gyrus. The histological and biochemical findings are interpreted as indicating that the entorhinal cortex of the rat provides the major extrinsic synaptic input to the hippocampal formation via the circuit which serves as a relay passage through the dentate gyrus and via direct projections into the hippocampus. Behavioral findings confirmed the importance of the entorhinal cortex in memory acquisition and indicated that rats with a partial neuronal loss in the entorhinal cortex may be a useful model for the memory disturbance of Alzheimer's disease.

Acetylcholine↗

Management of psychiatric symptoms of Parkinson's disease.

Depression and hallucination are the two main psychiatric symptoms in parkinsonian patients. Depressive features in Parkinson patients are very close to those of endogenous depression, except for a relative lack of anxiety, irritability, suicidal ideations, delusions and circadian rhythm. Pharmacotherapy with antidepressants is most reliable in the treatment of parkinsonian depressives, although levodopa or other antiparkinsonian drugs may relieve a depression. Hallucinatory complications of long-term antiparkinsonian treatment appear in two types of symptoms: (1) hallucinosis type-vivid visual hallucination and illusion with clear consciousness and well-preserved orientation, and (2) delirium type-less vivid visual hallucination and illusion with disturbed orientation and confusion. Antipsychotic drugs and 'drug holiday' are recommended for the management of hallucinations as side effects of antiparkinsonian drugs.

Adult↗

BMP signaling during bone pattern determination in the developing limb.

To examine the role of BMP signaling during limb pattern formation, we isolated chicken cDNAs encoding type I (BRK-1 and BRK-2) and type II (BRK-3) receptors for bone morphogenetic proteins. BRK-2 and BRK-3, which constitute dual-affinity signaling receptor complexes for BMPs, are co-expressed in condensing precartilaginous cells, while BRK-1 is weakly expressed in the limb mesenchyme. BRK-3 is also expressed in the apical ectodermal ridge and interdigital limb mesenchyme. BRK-2 is intensely expressed in the posterior-distal region of the limb bud. During digit duplication by implanting Sonic hedgehog-producing cells, BRK-2 expression is induced anteriorly in the new digit forming region as observed for BMP-2 and BMP-7 expression in the limb bud. Dominant-negative effects on BMP signaling were obtained by over-expressing kinase domain-deficient forms of the receptors. Chondrogenesis of limb mesenchymal cells is markedly inhibited by dominant-negative BRK-2 and BRK-3, but not by BRK-1. Although the bone pattern was not disturbed by expressing individual dominant-negative BRK independently, preferential distal and posterior limb truncations resulted from co-expressing the dominant-negative forms of BRK-2 and BRK-3 in the whole limb bud, thus providing evidence that BMPs are essential morphogenetic signals for limb bone patterning.

Amino Acid Sequence↗