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Biomedical subjects

M Mogi

Publications and source records attributed to M Mogi.

At least 37 records · Page 2Linked to original sources

Cytokines in Parkinson's disease.

We found that in Parkinson's disease (PD) the levels of various cytokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-2, IL-4, IL-6, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, TGF-beta1] were significantly increased in the striatum (caudate and putamen) of the postmortem brain and in ventricular or spinal cerebrospinal fluid (VCSF, LCSF). Furthermore, the levels of the apoptosis-related proteins such as bcl-2 and soluble Fas (sFas) in the striatum were also elevated in PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated parkinsonism mice, the levels of IL-1beta in the striatum were significantly increased, but those of nerve growth factor (NGF) were significantly decreased, compared with control mice. In hemiparkinsonism rats produced by injection of 6-hydroxydopamine (6-OHDA) into one side of the median forebrain bundle, the levels of TNF-alpha in the 6-OHDA-treated side were increased in the striatum and substantia nigra, but not in the cerebral cortex, compared with those in the control side. Repeated administration of L-DOPA in the 6-OHDA-treated rats did not change the TNF-alpha levels in the control side and in the 6-OHDA-treated side in the substantia nigra, striatum, and cerebral cortex. Our results suggest that the changes in the levels of cytokines, neurotrophins, and apoptosis-related proteins in the nigrostriatal regions of PD may be involved in apoptosis and degeneration of the nigrostriatal DA neurons.

Animals↗

Involvement of nitric oxide and biopterin in proinflammatory cytokine-induced apoptotic cell death in mouse osteoblastic cell line MC3T3-E1.

We previously demonstrated that the addition of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma) caused induction of mRNAs for inducible nitric oxide (NO) synthase and GTP cyclohydrolase I, a rate-limiting enzyme for 5,6,7,8-tetrahydrobiopterin (BH4) biosynthesis, and produced their end-products, NO and BH4, in osteoblastic cells. In the present study, we examined whether NO and BH4, biologically active substances produced in response to proinflammatory cytokines, are involved in the effect of these cytokines on cell viability and apoptotic cell death involving DNA fragmentation. Cytokines as well as S-nitroso-N-acetyl-d,l-penicillamine, an NO generator, decreased cell viability, whereas sepiapterin, which was converted intracellularly to BH4, increased it. The examination of cytotoxicity measured in terms of lactate dehydrogenase release and apoptotic cell death assessed by flow cytometric analysis showed that cytokine-induced reduction of cell viability may be based upon cell death by apoptosis, but not lytic death as in necrosis. In the presence of sepiapterin, cytokine treatment resulted in a statistically pronounced reduction in the amount of DNA fragmentation. Furthermore, this fragmentation could be blocked by 2-(4-carboxy-phenyl)-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide, an NO scavenger. These results suggest that cytokine-induced apoptotic cell death is attributed to NO and is protected by BH4, and that osteoblastic cells in response to proinflammatory cytokines operate both a stimulatory process resulting in NO production and an inhibitory one resulting in BH4 production for apoptotic cell death. Cytokine-induced apoptotic cell death may be a consequence of the predominance of the stimulatory process over the inhibitory process.

3T3 Cells↗

Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson's disease.

Using highly sensitive sandwich enzyme-linked immunosorbent assays (ELISA), we measured for the first time the concentrations of brain-derived growth factor (BDNF) in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients. BDNF in the human brain (the order of ng/mg protein) was significantly lower specifically in the nigrostriatal dopamine (DA) regions from parkinsonian patients than in those from control patients. The concentration of nerve growth factor (NGF) was also significantly decreased in the substantia nigra of parkinsonian patients in comparison with that in the controls. Since BDNF and NGF may play important roles in survival and differentiation of neuronal cells, the present data indicate that the lack of neurotrophins, especially BDNF, may be involved in the pathogenesis of PD during progress of neurodegeneration of the nigrostriatal DA neurons.

Adult↗

Increase in level of tumor necrosis factor (TNF)-alpha in 6-hydroxydopamine-lesioned striatum in rats without influence of systemic L-DOPA on the TNF-alpha induction.

We previously reported that the levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha are increased in the striatum and cerebrospinal fluid from patients with Parkinson's disease (PD) and in the striatum from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, a murine model of PD. Presently we examined the changes in cytokine levels in the nigrostriatal dopaminergic regions in rats treated with an intrastriatal injection of 6-hydroxydopamine (6-OHDA) as a model of slowly progressive neurodegeneration similar to that seen in PD. We compared the content of TNF-alpha in the nigrostriatal dopaminergic regions of the control side with that of the 6-OHDA-injected experimental side, and also explored the effects of 6-OHDA injection combined with the L-DOPA treatment on the TNF-alpha level in the dopaminergic regions of rats. TNF-alpha was measured by a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of TNF-alpha in the dopaminergic regions (striatum and substantia nigra) on the 6-OHDA injection side (right side: R) were significantly higher than those in the regions on the control side (left side: L) (Wilcoxon's test, P < 0.05). The ratio of the concentration of TNF-alpha on the injection side to that on the control side (TNF-alpha (R/L)) of each rat was not significantly different in the striatum and substantia nigra between the control group and the group treated with 25 or 50 mg/kg L-DOPA (Mann-Whitney Utests). These results show that TNF-alpha is increased in the striatum and substantia nigra in 6-OHDA-injected dopaminergic regions in rats, which finding is similar to the increase in the striatal dopaminergic regions in patients with PD. The results also indicate that L-DOPA alone or together with 6-OHDA does not increase the level of TNF-alpha in the brain in vivo.

Animals↗

Interleukin 1 beta, interleukin 6, beta 2-microglobulin, and transforming growth factor-alpha in gingival crevicular fluid from human periodontal disease.

Inflammatory mediators are central to the pathogenesis of periodontal diseases and may be used as markers in diagnosis. The aim of this study was to identify and quantify the various growth factors, apoptosis-related modifiers [soluble form of Fas (sFas) and bcl-2] and cytokines in the gingival crevicular fluid (GCF) of patients with different severities of periodontitis as compared with those of controls. GCF samples were taken from patients with periodontal disease and from controls. The concentrations of epidermal growth factor, transforming growth factor (TGF)-alpha, interleukin (IL)-1 beta, IL-6, interferon-gamma, beta 2-microglobulin (beta 2-MG), and apoptosis-related modifiers sFas and bcl-2 in the samples were determined by enzyme-linked immunosorbent assay. TGF-alpha was significantly lower in patients with periodontal disease than in the controls. In contrast, the concentrations of IL-1 beta, IL-6; and beta 2-MG were significantly higher in the group with severe periodontal disease than in the controls. The amount of total protein in the GCF was considerably higher in the disease group than the controls (p < 0.05). TGF-alpha, IL-1 beta, and beta 2-MG concentrations were associated (Spearman rank correlation, r < 0.05 for all) with clinical measures of disease severity (pocket depth) and inflammation (bleeding when probed). Apoptosis-related modifiers (sFas and bcl-2) could not be detected in any samples. These results suggest that the growth factor TGF-alpha and certain cytokines are associated with the presence of periodontal disease.

Adult↗

Differences in energy metabolism and adult desiccation resistance among three Aedes (Stegomyia) species (Diptera: Culicidae) from South Sulawesi, Indonesia.

To determine the mechanisms of adult desiccation resistance of Aedes (Stegomyia) species, we estimated the carbohydrate and lipid contents of newly emerged adult mosquitoes from South Sulawesi, Indonesia. Inter- and intraspecific differences in glycogen and free fatty acid accumulation were found in Aedes aegypti (L.), Ae. albopictus (Skuse), and Ae. paullusi (Stone & Farmer). High glycogen content was determined for both sexes in all Ae. aegypti strains and in the Ujung Pandang strain of Ae. albopictus. There were no differences among species in either trehalose or sorbitol content. A trend similar to glycogen was seen for lipid content, especially the free fatty acids of neutral lipids. These energy reserves of adult mosquitoes correlated with adult desiccation survival time at 90% RH calculated by Mogi et al. (1996). In both sexes, survival time was longer in strains with high glycogen and free fatty acid content, and low trehalose content. Ae aegypti, Ae. albopictus, and Ae. paullusi are species with high, intermediate, and low levels of glycogen and free fatty acids, respectively. However, longevity of these species under desiccation conditions is associated strongly with glycogen-trehalose conversion, and free fatty acid accumulation.

Aedes↗

Culex (Acallyntrum) miyagii (Diptera: Culicidae): new species from Seram Island, Indonesia, with keys to the species of the subgenus.

Culex (Acallyntrum) miyagii is described as a new species from Seram Island, Indonesia. The adult male, female, pupa, and larva are described in detail, and illustrations of the male genitalia, pupa, and larva are provided. Cx. miyagii is a forest species breeding in inflorescences of Costus sp. (Costaceae). Keys are provided for identifying the females and 4th-instar larvae of the species of Acallyntrum.

Animals↗

Anti-proliferative capsular-like polysaccharide antigen from Actinobacillus actinomycetemcomitans induces apoptotic cell death in mouse osteoblastic MC3T3-E1 cells.

Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) has been implicated in the etiology of localized juvenile periodontitis (LJP), and produces a multiplicity of tissue-damaging products. Among those products, the capsular-like polysaccharide antigen (CPA) from A. actinomycetemcomitans is a potent mediator of bone resorption. In fact, this CPA (serotype b) is known to promote osteoclast-like cell formation via interleukin (IL)-1alpha production in mouse marrow cultures. Although osteoblasts complete bone formation, there are few reports focusing on the effect of CPA in bone-forming activity of osteoblasts in inflammatory disease sites. We hypothesized that CPA plays a mediating role in osteoblastic cells. Therefore, the purpose of this study was to examine the effect of CPA from A. actinomycetemcomitans on the mouse osteoblastic cell line MC3T3-E1 and human osteosarcoma SaOS-2 cells. A. actinomycetemcomitans serotype c resulted in a potent dose-dependent inhibition of cell proliferation of both cell lines. Characterization of the antiproliferative activity in the CPA demonstrated that it was not cytotoxic for MC3T3-E1. A 20-hour incubation with CPA-c resulted in a significant increase in apoptotic cell death in the cells, as evaluated by both cellular DNA fragmentation ELISA and FACS analysis. In contrast to the results obtained with a cytokine mixture (tumor necrosis factor-alpha, IL-1beta, and interferon-gamma), no inducible nitric oxide (NO) synthase gene expression or NO release could be detected in MC3T3-E1 after incubation with CPA-c. Further, both CPA-b and -c caused potent induction of apoptosis-related modifiers, e.g., Fas mRNA, whereas bcl-2 mRNA levels were unchanged. Therefore, this study has shown that CPA from A. actinomycetemcomitans contains a potent antiproliferative polysaccharide whose activity is associated with apoptotic cell death in MC3T3-E1, and that CPA per se is an inducer of apoptosis mediated by the Fas system but not by NO.

Aggregatibacter actinomycetemcomitans↗

Mosquito and aquatic predator communities in ground pools on lands deforested for rice field development in central Sulawesi, Indonesia.

Aquatic habitats, mosquitoes, and larvivorous predators were studied on deforested lands in Central Sulawesi, Indonesia. Open ground pools, mainly in depressions made by the treads of bulldozers and other heavy equipment, were numerous but because of their small size, comprised ca. 1% or less of the total area of the deforested lands studied. The dominant mosquitoes in these pools were Anopheles vagus, Culex vishnui, Culex tritaeniorhynchus, and Culex gelidus. The 1st 2 species were dominant in clear pools, whereas the latter 2 species were dominant in turbid pools. The dominant metazoans other than mosquitoes were Crustacea, Ephemeroptera, and Chironomidae. Both aquatic and surface predators were abundant. Dominant among aquatic predators were Anisoptera and Zygoptera nymphs, Dytiscidae, and Notonectidae. These results are discussed in relation to mosquito control on deforested lands that transitionally but inevitably appear during the course of rice field development projects in Indonesia.

Agriculture↗

Mosquito immatures in drought-prone and drought-resistant bamboo stumps in Flores, Indonesia.

Mosquito species in water-filled bamboo stumps were compared with those emerged from dormant eggs in dry stumps. Tripteroides spp. was more abundant than Aedes (Stegomyia) spp. (mainly annandalei and albopictus) in water-filled stumps, whereas the latter was more abundant than the former in dry stumps. During 5 days after inundation, Aedes (Stegomyia) spp. developed faster than Tripteroides spp. Density of Tripteroides spp. was high in narrow and deep stumps. Both taxa of mosquitoes were at low densities in water-filled stumps with large detritivores (Tipulidae and Oligochaeta).

Aedes↗

Questionnaire survey and prevalence of intestinal helminthic infections in Barru, Sulawesi, Indonesia.

A questionnaire survey with parasitological study was carried out on the inhabitants of 4 villages in Barru district, Sulawesi, Indonesia from 1994 to 1995. The questionnaire dealt with life style and sanitary conditions. In 482 houses in the 4 villages, interviews for the items of the questionnaire were conducted with the owner, housekeeper and children of the same family. In Pancana and Lalolang, 37.7% and 50% respectively of man inhabitants surveyed were fishermen, while in Lompo Riaja and Pattappa, 38.6% and 65.5% respectively were farmers. The highest proportion of official workers was 33.7% in Lompo Riaja. Educational level was low; 88.4% in Pancana, 90.4% in Lalolang, 62.1% in Lompo Riaja and 91.2% in Pattappa had elementary or below elementary school education. In Lompo Riaja, 30.8% of the inhabitants graduated from senior high school or university. The percentage of families having their own latrine was 30.3% in Pancana, 13.2% in Lalolang, 31.9% in Pattapa and 60% in Lompo Riaja. The people without latrines usually defecated in rice fields, seaside or riverside. A total of 654 fecal samples was examined by the modified Kato-Katz thick smear method. Five nematode species, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, Strongyloides stercoralis and unidentified Rhabditoids of free-living nature were detected. Cestode, Hymenolepis nana infection was confirmed. All the hookworms examined by the modified Harada-Mori culture technic were Necator americanus. Trichuris infection was most common, followed by hookworm and Ascaris infections, both in young (aged 4-14) and older (aged over 15) age groups. The prevalence of hookworm infection was significantly higher in males than in females of older age. Among the older age group, the prevalence of Trichuris infection was significantly lower in Lompo Riaja, while hookworm infection was the highest in Pattappa. Among all the inhabitants examined for parasite infection, 17.4% had 3 kinds of nematode, Ascaris, Trichuris and hookworm. However, egg counts revealed that most of the inhabitants with Trichuris or hookworm had light infections. The inhabitants with higher education background had significantly lower infection rates of Ascaris and Trichuris. The prevalence of hookworm infection was not significantly different between the inhabitants owning latrine and without it, but the prevalence of Ascaris and Trichuris, differed significantly.

Adolescent↗

Effects of repeated systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mice on interleukin-1beta and nerve growth factor in the striatum.

Interleukin (IL)-1beta and nerve growth factor (NGF) were measured for the first time in the brain (caudate nucleus and putamen, and frontal cortex) from control mice and mice treated with a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), by highly-sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) The concentrations of interleukin (IL)-1beta in the striatal regions were significantly higher in MPTP-treated mice than those in control mice treated with saline (P < 0.005), whereas those in the frontal cortex did not show significant differences between MPTP-treated and control mice. The present results agreed with our previous data on increased IL-1beta in the postmortem striatum from patients with Parkinson's disease (PD). In contrast, the concentrations of nerve growth factor (NGF) in the striatal regions were significantly lower in MPTP-treated mice, down to a 54% level of control mice (P < 0.05), but those in the frontal cortex did not show significant differences between MPTP-treated and control mice. Since NGF may play important roles as neurotrophic factors in the brain, the present results suggest that both the elevation of pro-inflammatory cytokine IL-1beta and the decrease of NGF in the dopaminergic striatal region of MPTP- treated mice may be related to neuronal cell death.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Coexpression of GTP cyclohydrolase I and inducible nitric oxide synthase mRNAs in mouse osteoblastic cells activated by proinflammatory cytokines.

Proinflammatory cytokines, a combination of IL-1beta, TNF-alpha, and IFN-gamma, caused mRNA expression of GTP cyclohydrolase I (GTP-CH), the rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, and of inducible nitric oxide synthase (iNOS) in a well-characterized osteoblastic clone MC3T3-E1 cell line. We found the expression of the GTP-CH gene in osteoblasts for the first time. The expression of GTP-CH and iNOS mRNAs was found to be maximal at 3 and 9 h, respectively. The expression of both genes elicited increases in BH4 and NO levels. Pharmacological studies using 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP-CH activity, showed that BH4 is involved in the activity of iNOS, but not in the induction of iNOS mRNA. The results using an inhibitor of nuclear factor (NF)-kappaB and activating protein-1 (AP-1) activation suggested that coinduction of the two genes in response to cytokines occurred via activation of NF-kappaB and AP-1. In MC3T3-E1 cells BH4 and sepiapterin, producing BH4, could protect against apoptosis, i.e. the degradation of nuclear DNA in the cells, induced by NO derived from S-nitroso-N-acetyl-D-L-penicillamine. These results suggest that the induction of BH4 together with NO by proinflammatory cytokines could protect against NO-induced apoptosis in MC3T3-E1 cells.

3T3 Cells↗

[High-performance liquid chromatographic method for the determination of fenofibric acid and reduced fenofibric acid in human blood, plasma and urine].

In this study, a very reliable HPLC method was developed for the determination of fenofibric acid and reduced fenofibric acid in the biological samples described as follows. After addition of the internal standard solution and 0.5 M HCl to the biological sample, fenofibric acid, reduced fenofibric acid and the internal standard were extracted with a mixed solvent of n-hexane and ethyl acetate (90:10) from the mixture. The acids were back-extracted from the organic phase with 0.1 M Na2HPO4 and then re-extracted from the aqueous phase with a mixed solution of n-hexane and ethyl acetate (95:5) after addition of 0.5 M HCl. The organic phase was evaporated to dryness under the vacuum. The residue was dissolved in MeOH and diluted with distilled water. An aliquot of the resulting solution was injected on the HPLC. High reproducibility was observed in this HPLC method (C.V.% less than 4%). Moreover it was confirmed that the conjugates in the urine could be hydrolyzed by incubation at 37 degrees C for 18 h after addition of 400 IU of beta-glucuronidase.

Administration, Oral↗

The soluble form of Fas molecule is elevated in parkinsonian brain tissues.

Fas is an apoptosis-signaling receptor molecule on the surface of a number of cell types. The soluble form of Fas (sFas) was measured for the first time in brain (caudate nucleus, putamen and cerebral cortex), ventricular cerebrospinal fluid (VCSF), and lumbar CSF (LCSF) from control and parkinsonian patients by a highly sensitive two-site sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of sFas in nigro-striatal dopaminergic regions were significantly higher in parkinsonian patients than those in controls, whereas this product in cerebral cortex showed no significant difference between parkinsonian and control subjects. Neither VCSF nor LCSF contained the sFas molecule in the detectable amounts (< 16 pg/ml). These results suggest that the presence of sFas possibly leads to cell death/neurodegeneration in parkinsonian brain.

Aged↗

bcl-2 protein is increased in the brain from parkinsonian patients.

The proto-oncogene bcl-2 is involved in the regulation of cell death and may be able to block apoptosis in neurons through reduced generation of reactive oxygen species (ROS). The bcl-2 product was measured for the first time in brain (caudate nucleus, putamen and cerebral cortex), ventricular cerebrospinal fluid (VCSF), and lumber CSF (LCSF) from control and parkinsonian patients by highly sensitive two-site sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of bcl-2 in the nigrostriatal dopaminergic regions were significantly higher in parkinsonian patients than those in controls, whereas this product in cerebral cortex showed no significant difference between parkinsonian and control subjects. Neither VCSF nor LCSF from control or parkinsonian subjects contained the bcl-2 product in the detectable amount (< 5 U/ml). Since oxidative stress may be involved in neurogenerative disorders, accumulation of bcl-2 may reflect a mechanism for counterbalancing ROS-mediated damage, or it might represent the impairment of bcl-2-dependent protection from ROS in parkinsonian brain.

Aged↗

Selective removal of human serum amyloid P component from rat blood by use of an immunoaffinity membrane in an extracorporeal circulation system.

We examined the suitability of an immunoaffinity membrane (IAM) bearing specific antibody as a ligand for removing human serum amyloid P component (hSAP) from blood passed through a simple extracorporeal circulation system established in rats. The specific antibody was the most effective of the various ligands tested for removing hSAP from human blood. To determine the value of the hSAP in human or rat plasma, we also developed a simple ELISA. In the rat extracorporeal circulation system, the hSAP level in the inlet blood to the IAM module decreased to 49% of the initial concentration within 60 min. In contrast, the hSAP remained at the initial concentration throughout the study in the module without the IAM. The use of this extracorporeal circulation system in this case allows preclinical evaluation of the ex vivo removal of a human plasma component in an animal model. Biocompatibility of the IAM was also examined. No change in blood cell counts or activation of the coagulation system occurred after contact with the IAM. Non-specific adsorption was not observed, since there was no statistically significant difference in IgG, complement C3, or albumin level between the pre- and post-treatment with this module. The immunological effects of the IAM were also examined using this system. Four weeks after the termination of the extracorporeal circulation, the rats examined showed no detectable antibody titer to the ligand.

Adsorption↗