Inhibitory effect of cathepsin B inhibitor CA 074 on mouse anti-rat mixed lymphocyte reaction: novel immunosuppressive strategy for indirect xenoantigen recognition.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
K Honda
Publications and source records attributed to K Honda.
Serum and bile individual bile acid changes as a noninvasive marker of small bowel allograft rejection in rats.
Explore the source record for details and available documents.
Animals↗
Effect of tacrolimus in renal transplant recipients with immunoglobulin-A nephropathy.
Explore the source record for details and available documents.
Adult↗
Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: a study of D- and L-derivatives in canine narcolepsy.
Using a canine model of narcolepsy and selective DA and NE uptake inhibitors, we have recently shown that DA uptake inhibition promotes wakefulness, while NE uptake inhibition inhibits rapid eye movement sleep and cataplexy. In order to further delineate the respective roles of the dopaminergic and noradrenergic systems in the pharmacological control of symptoms of narcolepsy, we compared the potency of amphetamine isomers (D- and L-amphetamines) and a derivative (L-methamphetamine) on wakefulness and cataplexy. Their respective effects on these narcolepsy symptoms were then compared with their in vivo effects on extracellular DA levels in the caudate and NE levels in the frontal cortex during local drug perfusion in narcoleptic dogs. Polygraphic recordings demonstrated that D-amphetamine was about twice as potent as L-amphetamine, and was six times more potent than L-methamphetamine in increasing wakefulness and reducing slow-wave sleep. D-Amphetamine and L-amphetamine were equipotent in reducing rapid eye movement sleep and cataplexy, and L-methamphetamine was about half as potent as L- and D-amphetamines. D-Amphetamine was found to be more potent in increasing DA efflux than L-amphetamine, and L-methamphetamine was found to have little effect on DA efflux; there was no significant difference in the potencies of the three derivatives on NE efflux. The potencies of these amphetamines on wakefulness correlated well with DA, but not NE, efflux in the brain of narcoleptic dogs during local drug perfusion. Our current results further exemplify the importance of the DA system for the pharmacological control of electroencephalogram arousal and suggest that increased DA transmission mediates the wake-promoting effects of amphetamine-like stimulants.
Amphetamine↗
Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy.
The effects on cataplexy and daytime sleep of acute and chronic oral administration of CG-3703, a potent TRH analog were assessed in canine narcolepsy. CG-3703 was found to be orally active and to reduce cataplexy (0.25 to 16 mg/kg) and sleep (8 and 16 mg/kg) in a dose-dependent manner. Two-week oral administration of CG-3703 (16 mg/kg) significantly reduced cataplexy and daytime sleep. The anticataplectic effects of CG-3703 were not associated with changes in general behavior, heart rate, blood pressure, rectal temperature, blood chemistry and thyroid function. Although drug tolerance for the effects on cataplexy and sleep were observed during the second week of chronic drug administration, therapeutic efficacy on cataplexy was improved with individual dose adjustment (final dose range: 16 to 28 mg/kg, p.o.). These results suggest that TRH analogs could be a promising new form of treatment for human narcolepsy.
Animals↗
Single-sweep EEG analysis of neural processes underlying perception and production of vowels.
This single-sweep electroencephalographic study using independent component analysis was conducted to determine the neural processes underlying both speech perception and production of vowels. The same neural processes located in auditory and motor areas of the brain that significantly distinguish between a speech production and a control mental rehearsal task were found for both auditory evoked responses and speech planning responses. Thus identifying common task dependent neural processes underlying speech production and perception.
Adult↗
Inflammation, a prototype for organogenesis of the lymphopoietic/hematopoietic system.
Explore the source record for details and available documents.
Bone Marrow↗
Patterns and mechanisms of pedestrian injuries induced by vehicles with flat-front shape.
To clarify the difference between flat-front vehicles and bonnet-front vehicles with regard to the patterns and mechanisms of vehicle-induced pedestrian injuries, we investigated 101 cases of pedestrians who were struck by the front of a vehicle. There were 33 flat-front vehicle collision cases and 68 bonnet-front vehicle collision cases. The frequency of chest injuries in flat-front vehicle collisions (30.3%) was significantly higher than that in bonnet-front vehicle collisions (11.8%). Lower leg fractures were more common in bonnet-front vehicle collisions than in flat-front vehicle collisions. Although head injuries were common in both cases, the mechanisms of these injuries differed. The pedestrians who were struck by flat-front vehicles tended to sustain more severe injuries at lower impact speeds. All of these results stem from the difference in the front shape of the two types of vehicle. Pedestrians who are struck by the front of flat-front vehicles receive the impact force to the trunk, particularly the chest, at the initial impact and are thrown out forward after the impact, because the front of these vehicles is perpendicular to the road.
Journal Article↗
Kinmoonosides A-C, three new cytotoxic saponins from the fruits of Acacia concinna, a medicinal plant collected in myanmar.
Three genuine saponins, named kinmoonosides A-C (1-3), have been isolated, together with a new monoterpenoid (4), from a methanolic extract of the fruits of Acacia concinna. The structures of kinmoonosides A-C were elucidated on the basis of spectral analysis as 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-¿(6R, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinovopyranosyl]-2, 7-octadienoyl¿acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (1); 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-¿(6S, 2E)-2-hydroxymethyl-6-methyl-6-O-[4-O-(2'E)-6'-hydroxyl-2'-hydroxymet hyl-6'-methyl-2',7'-octadienoyl-beta-D-quinobopyranosyl]-2, 7-octadienoyl¿acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (2); and 3-O-¿alpha-L-arabinopyranosyl(1-->6)-[beta-D-glucopyranosyl(1-->2) ]-b eta-D-glucopyranosyl¿-21-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl- 2,7-octadienoyl]acacic acid 28-O-alpha-L-arabinofuranosyl(1-->4)-[beta-D-glucopyranosyl(1-->3)]-a lpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester (3), respectively. The new monoterpenoid 4 was determined as 4-O-[(2E)-6-hydroxyl-2-hydroxymethyl-6-methyl-2, 7-octadienoyl]-D-quinovopyranose. Compounds 1-3 showed significant cytotoxicity against human HT-1080 fibrosarcoma cells.
Antineoplastic Agents, Phytogenic↗
Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation.
The contribution of the thymus-dependent pathway and thymus-independent pathways for T cell regeneration after BMT in children is still unclear. We analyzed the kinetics of T cell regenerative pathways after allogeneic BMT. The number of CD4+CD45RA+ T cells, a thymus-dependent population, was very low until 3 months after BMT. The numbers of CD28- T cells and CD8+ T cells expressing CD8alpha/alpha homodimer (CD8alpha/alpha+ T cells), a thymus-independent population, increased shortly after BMT, beyond the levels of healthy children in some patients. The numbers of Vgamma9+Vdelta2+ and Valpha24+ T cells, which represent populations of extrathymic development, were less than 200/microl during the 6 months after BMT. There was a significant inverse correlation between the percentages of CD4+CD45RA+ and CD28-T cells at 1 month, and a positive correlation between the percentages of CD28- and CD8alpha/alpha+ T cells at 2 and 3 months after BMT. The mean age at BMT was higher in patients with a high level of CD8alpha/alpha+ T cells than in those without an increase in these cells, suggesting the influence of thymic function on the regenerative pathways. These results suggest that the thymus-independent pathway is the dominant source of T cells even in children shortly after allogeneic BMT.
Acute Disease↗
New p53 mutations in hilar cholangiocarcinoma.
BACKGROUND: Inactivation of the tumour suppressor gene, p53, is the commonest genetic abnormality in human cancer. The study of the type of p53 mutation in a given tumour may provide prognostic information, clues to aetiology and become useful for therapeutics. MATERIALS AND METHODS: The molecular characterisation of p53 was performed by restriction analysis, denaturing gradient gel electrophoresis, and gene sequencing for exons 5-9. RESULTS: We report, p53 mutational analysis in exons 5-9 in 29 European patients with hilar cholangiocarcinoma who underwent attempted resection. Four patients (14%) showed somatic single nucleotide substitutions with amino acid changes (146, 163, 175, 158, and 175) with one showing mutations in two different positions involving a loss of two CfoI sites. All the mutations occurred in exon 5. Three patients had a germline polymorphism (10%) with a silent substitution in codon 213 (exon 6). CONCLUSIONS: The systematic screening for p53 mutations in European patients with hilar cholangiocarcinoma has shown that the type of mutation (except 175) is different and its incidence is much lower when compared to the pattern previously reported for intrahepatic cholangiocarcinoma in East Asian patients. A probable explanation is that the presence and type of p53 mutation is dependent on geographic and environmental factors which vary in different populations.
Adult↗
3,4-Dihydrocoumarin hydrolase with haloperoxidase activity from Acinetobacter calcoaceticus F46.
A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of 3,4-dihydrocoumarin, was purified 375-fold to apparent homogeneity, with a 22.7% overall recovery, from Acinetobacter calcoaceticus F46, which was isolated as a fluorene-assimilating micro-organism. The molecular mass of the native enzyme, as estimated by high-performance gel-permeation chromatography, is 56 kDa, and the subunit molecular mass is 30 kDa. The enzyme specifically hydrolyzes 3,4-dihydrocoumarin, and the Km and Vmax for 3,4-dihydrocoumarin are 0.806 mM and 4760 U.mg-1, respectively. The N-terminal and internal amino acid sequences of the enzyme show high similarity to those of bacterial non-heme haloperoxidases. The enzyme exhibits brominating activity with monochlorodimedon in the presence of H2O2 and 3, 4-dihydrocoumarin or an organic acid, such as acetate and n-butyrate.
Acids, Acyclic↗
Serum markers of graft-versus-host disease after bone marrow transplantation.
BACKGROUND: Graft-versus-host disease is one of the major complications after allogenic bone marrow transplantation, but it is not easy to anticipate the onset. OBJECTIVES: The purpose of this study was to determine clinically useful markers of acute graft-versus-host disease. METHODS: We measured the serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble c-kit, soluble Fas, soluble intercellular adhesion molecule-1, growth-related oncogene protein-alpha, thrombomodurin, and interleukin-16 in 13 patients at 1 to 7 weeks after allogenic bone marrow transplantation. RESULTS: The patients with acute graft-versus-host disease showed a significant increase of tumor necrosis factor, soluble tumor necrosis factor receptor 1, soluble Fas, soluble intercellular adhesion molecule-1, and growth-related oncogene protein-alpha, although there was a decrease of soluble c-kit. The increases of serum soluble tumor necrosis factor receptor 1, intercellular adhesion molecule-1, and growth-related oncogene protein-alpha were preceded by the elevation of soluble Fas. CONCLUSION: The patients with acute graft-versus-host disease had increased serum levels of tumor necrosis factor-alpha, soluble tumor necrosis factor receptor 1, soluble Fas, and soluble intercellular adhesion molecule 1 and a decreased soluble c-kit level. Tumor necrosis factor-alpha and soluble c-kit were shown to be sensitive and specific parameters for graft-versus-host disease after bone marrow transplantation, and soluble Fas was shown to be a predictor of acute graft-versus-host disease after bone marrow transplantation.
Adolescent↗
Signaling through the beta2 integrin prolongs eosinophil survival.
BACKGROUND: Recently, adhesion molecules have been suggested to play an important role in allergic inflammatory diseases such as bronchial asthma. It is unclear whether eosinophil activation and paracrine or autocrine synthesis of eosinophilopoietic growth cytokines is mediated through signaling by intercellular adhesion molecule-1 (ICAM-1) and the beta2 integrin family. OBJECTIVE: We examined whether signaling by ICAM-1 and its ligands (beta2 integrins) could prolong eosinophil survival. METHODS: Eosinophils were isolated from patients with hypereosinophilia by modified CD16 negative selection. After culture with or without recombinant soluble ICAM-1, eosinophil viability was measured by trypan blue dye exclusion. RESULTS: Eosinophil survival was prolonged in cultures with recombinant soluble ICAM-1 compared with cultures without it (P <.01 on days 2, 4, and 6); this effect was dose-dependent. Eosinophil survival in cultures with recombinant soluble ICAM-1 was significantly inhibited by antibodies against ICAM-1 (P <.01), complement receptor 3 (P <.01), and lymphocyte function-associated antigen-1beta (P <.01). Anti-IL-3 showed no effect on eosinophil survival, whereas anti-IL-5 caused partial inhibition of survival. Interestingly, anti-granulocyte/macrophage colony-stimulating factor caused the complete inhibition of eosinophil survival in cultures with recombinant soluble ICAM-1. CONCLUSION: These results suggested the importance of the beta2 integrins in eosinophil-mediated allergic inflammation.
Cell Survival↗
The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes.
Excessive mechanical load is thought to be responsible for the onset of osteoarthrosis (OA), but the mechanisms of cartilage destruction caused by mechanical loads remain unknown. In this study we applied a high magnitude cyclic tensile load to cultured chondrocytes using a Flexercell strain unit, which produces a change in cell morphology from a polygonal to spindle-like shape, and examined the protein level of cartilage matrixes and the gene expression of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and proinflammatory cytokines such as IL-1beta and TNF-alpha. Toluidine blue staining, type II collagen immunostaining, and an assay of the incorporation of [35S]sulfate into proteoglycans revealed a decrease in the level of cartilage-specific matrixes in chondrocyte cultures subjected to high magnitude cyclic tensile load. PCR-Southern blot analysis showed that the high magnitude cyclic tensile load increased the mRNA level of MMP-1, MMP-3, MMP-9, IL-1beta, TNF-alpha and TIMP-1 in the cultured chondrocytes, while the mRNA level of MMP-2 and TIMP-2 was unchanged. Moreover, the induction of MMP-1, MMP-3 and MMP-9 mRNA expression was observed in the presence of cycloheximide, an inhibitor of protein synthesis. These findings suggest that excessive mechanical load directly changes the metabolism of cartilage by reducing the matrix components and causing a quantitative imbalance between MMPs and TIMPs.
Animals↗
Mechanisms of antiapoptotic effects of estrogens in nigral dopaminergic neurons.
Parkinson's disease is characterized by the mesencephalic dopaminergic neuronal loss, possibly by apoptosis, and the prevalence is higher in males than in females. The estrogen receptor (ER) subtype in the mesencephalon is exclusively ER beta, a recently cloned novel subtype. Bound with estradiol, it enhances gene transcription through the estrogen response element (ERE) or inhibits it through the activator protein-1 (AP-1) site. We demonstrated that 17beta-estradiol provided protection against nigral neuronal apoptosis caused by exposure to either bleomycin sulfate (BLM) or buthionine sulfoximine (BSO). BLM and BSO-induced nigral apoptosis was blocked by inhibitors for caspase-3 or c-Jun/AP-1. The antiapoptotic effect by estradiol was blocked by ICI 182,780, an antagonist for ER, but not by a synthesized peptide that inhibits binding of the ER to the ERE. Estradiol had no effects on caspase-3 activation and c-Jun NH(2)-terminal kinase (JNK), which were activated by BLM. It also suppressed apoptosis by serum deprivation, which was independent of caspase-3 activation. Therefore, the antiapoptotic neuroprotection by estradiol is mediated by transcription through AP-1 site downstream from JNK and caspase-3 activation. Furthermore, 17alpha-estradiol, a stereoisomer without female hormone activity, also provided an antiapoptotic effect. Therefore, the antiapoptotic effect is independent of female hormone activity.
Animals↗
Antitumor activity of 2-amino-4,4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one against Meth A tumor transplanted into BALB/c mice.
We examined the in vivo effect of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3- one (Phx) on Meth A carcinoma cells transplanted into BALB/c mice, in terms of both antitumor activity and side effects. Phx, which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemolysates, was administered i.p. at doses of 1 and 5 mg/kg to BALB/c mice transplanted with Meth A tumor cells. Phx exerted a strong antitumor activity to Meth A tumor growing in the mice as 5-fluorouracil (5-FU) did. The antitumor activity of Phx at the dose of 5 mg/kg was comparable to that of 5-FU at the dose of 7.8 mg/kg. In contrast, unlike 5-FU, Phx did not cause leukopenia while showing a strong antitumor activity. The compound also produced little changes in body weight and no wasting of mice developed. These results show that Phx has strong anti-tumor activity, but exerts lower side effects and suggest that Phx is available for therapeutic purposes in the future.
Animals↗
Excellent results of postoperative radiotherapy for endometrial stromal sarcoma of low-grade malignancy.
Endometrial stromal sarcoma of low-grade malignancy (ESSL) is a rare neoplasm, and neither preoperative diagnostic procedures nor standard therapy have yet been established. We treated 3 cases of ESSL in the past 27 years, and we report here one of these cases that was classified as stage III (according to the FIGO classification of endometrial carcinoma). Postoperative radiotherapy was used to treat a residual tumor, and the patient showed a complete response.
Adult↗