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Biomedical subjects

T Koga

Publications and source records attributed to T Koga.

At least 271 records · Page 15Linked to original sources

Actinobacillus actinomycetemcomitans serotype b-specific polysaccharide antigen stimulates production of chemotactic factors and inflammatory cytokines by human monocytes.

Serotype b-specific polysaccharide antigen (SPA) was extracted from whole cells of Actinobacillus actinomycetemcomitans Y4 by autoclaving and purified by chromatography on DEAE-Sephadex A-25 and Sephacryl S-300. SPA induced the release of monocyte and leukocyte chemotactic factors by human monocytes. Polymyxin B had almost no effect on the release of monocyte chemotactic factor, but a monoclonal antibody against SPA markedly inhibited it. Human monocytes stimulated with SPA exhibited the increased mRNA expression of monocyte chemoattractant protein 1 (MCP-1) and a neutrophil chemotactic factor, interleukin-8 (IL-8). On the other hand, SPA induced the release of IL-1, IL-6, and tumor necrosis factor (TNF) and enhanced the expression of IL-1alpha, IL-1beta, IL-6, and TNF alpha (TNF-alpha) mRNAs. Human monocytes expressed MCP-1 and IL-8 mRNAs when stimulated by human recombinant IL-1alpha, I1-1beta, IL-6, and TNF-alpha, suggesting that these inflammatory cytokines induced by SPA might participate in the production of chemotactic factors in human monocytes.

Aggregatibacter actinomycetemcomitans↗

Antioxidant behaviors of vitamin E analogues in unilamellar vesicles.

The antioxidant behaviors of vitamin E and its analogues, 2,2,5,7,8-pentamethyl-6-hydroxychroman and 1,2-diacyl-sn-glycero3-phospho-2'-(hydroxyethyl)-2'- 5',7',8'-tetramethyl-6'-hydroxychroman, were studied in unilamellar vesicles. The two analogues scavenged aqueous radicals generated from azo compounds more efficiently than vitamin E. On the other hand, vitamin E scavenged the lipid peroxyl radicals preferentially. It is concluded that the superior antioxidant activity of vitamin E is attributed to its location suitable for breaking the chain propagation reaction.

Antioxidants↗

Epi-cochlioquinone A, a novel acyl-CoA : cholesterol acyltransferase inhibitor produced by Stachybotrys bisbyi.

A novel acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, designated epi-cochlioquinone A has been isolated from the fermentation broth of Stachybotrys bisbyi SANK 17777. The molecular formula, physicochemical properties, NMR spectroscopic analysis and X-ray crystallographic analysis revealed that this compound was a stereoisomer of cochlioquinone A, which has been previously reported as a nematocidal agent. It inhibited ACAT activity in an enzyme assay using rat liver microsomes with an IC50 value of 1.7 microM. However, it showed about 10-fold less potent inhibitory effect on plasma lecithin cholesterol acyltransferase (LCAT) than on ACAT. In addition, it inhibited in vivo cholesterol absorption in rats by 50% at 75 mg/kg.

Animals↗

Osteoclasts in normal and adjuvant arthritis bone tissues express the mRNA for both type I and II interleukin-1 receptors.

Osteoclasts are known to play a crucial role in both physiologic and pathologic bone resorption. Moreover, it is generally agreed that IL-1 has powerful effects on osteoclastic bone resorption, although the precise cellular sites and mechanisms by which IL-1 mediates osteoclastic bone resorption remain unclear. In particular, it is still controversial whether osteoclasts can respond to IL-1 directly. The expression of mRNA for type I IL-1 receptor (IL-1RI) and type II IL-1 receptor (IL-1RII) in osteoclasts was investigated in normal and inflammatory bone tissues by in situ hybridization to determine whether osteoclasts are the target cells for IL-1 and to elucidate the mechanism by which IL-1 induces osteoclastic bone resorption. For this study, normal tibiae were obtained from newborn, young, and adult mice and rats, and inflammatory bone tissues with bone destruction were obtained from adjuvant arthritis rat models. The results showed that (a) both IL-1 receptors (IL-1RI and -II) mRNA were expressed by osteoclasts in all tissue sections of normal tibiae; (b) at the stage of the adjuvant arthritis studied, the IL-1RI mRNA was the most predominant message in osteoclasts present in the area with serious cartilage and bone destruction, whereas the expression level of IL-1RII mRNA in these osteoclasts was weak; and (c) both IL-1RI and -II mRNA were expressed by osteoblasts, as well as by osteocytes localized in the osteoid. In addition, these messages were also expressed by chondrocytes, but the signals were not detected in the chondrocytes in the zones of hypertrophy and provisional calcification. Our present study demonstrates for the first time that mouse and rat osteoclasts express IL-1RI and -II mRNA, which suggest that a primary effect of IL-1 on osteoclasts may be one of the mechanisms by which IL-1 mediates normal bone remodeling and pathologic bone resorption in chronic inflammatory diseases.

Animals↗

Light microscopic histochemical and immunohistochemical localisation of sulphated glycosaminoglycans in the rooster comb and wattle tissues.

Comb and wattle tissues, which consist of layers of epidermis, dermis and central connective tissue, are known to contain sulphated glycosaminoglycans (GAGs) including dermatan sulphate and chondroitin sulphate-dermatan sulphate copolymers. Little is known about distribution of these CAGs in each tissue. The objective of this study was to localise sulphated GAGS in the comb and wattle tissues from mature roosters. Monoclonal antibodies 6D6, CS-56 and AH12 specific to dermatan sulphate proteoglycan (decorin), chondroitin sulphate and keratan sulphate, respectively, were used. In both tissues, 6D6 epitope was found to be more concentrated in the superficial layer of dermis and the central connective tissue than in the intermediate layer of dermis containing fibromucoid tissue. The staining pattern for 6D6 epitope was similar to that for collagen fibres. In contrast, CS-56 epitope was uniformly distributed in most parts of the dermis and the central connective tissue. The stratum germinativum in the epidermis was the major tissue showing positive staining with AH12, haematoxylin and safranin-O.

Animals↗

Suppression of age-related changes in mouse hippocampal CA3 nerve cells by a free radical scavenger.

This study was designed to evaluate the relationship between oxygen free radicals and age-related morphological changes in hippocampal nerve cells using K-7259 (N,N' bis[4-(3,4,5-trimethoxyphenyl)butyl] homopiperazine dihydrochloride), a known neuro-protective agent. A chemiluminescence assay has shown that this agent is a potent free radical scavenger with an IC50 of 1.6 x 10(-5)M. Mice fed diets containing 10, 20, 40 mg/kg/day of K-7259, for periods ranging from 25 to 40 or 50 weeks of age were used as test groups, and 10-, 20-, 30-, 40-, and 50-week-old mice fed a standard diet were used as controls. We measured the number and area of pyramidal nerve cells within a defined frame in the hippocampal CA3 field using an image analyzer and the density of nerve cells by the disector method. These values decreased gradually in controls as expected, and the number and area yielded a significant difference between control mice at the ages of 10 and 30 weeks. As compared with the corresponding controls, all test groups had greater cell numbers (statistical significance at 40 weeks in the 40 mg/kg/day group) and density, while cell areas were greater in all but a 10 mg/kg/day group (statistical significance at 50 weeks). In summary, the free radical scavenger K-7259 forestalled an age-related decrease in the number and size of hippocampal CA3 nerve cells, thus suggesting that free radicals play an important role in the cellular morphological changes which appear with age.

Aging↗

Construction of a series of pACYC-derived plasmid vectors.

A series of cloning vectors has been constructed from pACYC177 and pACYC184. These vectors contain a MCS, the lacZ alpha reporter gene, and P15A ori. Plasmids pMBL18, pMBL19 and pMBLcos express the bla gene encoding ampicillin resistance, while pMCL200 and pMCL210 contain the cat gene encoding chloramphenicol resistance. In addition, the cosmid pMBLcos was constructed with the P15A ori. These vectors are useful for cloning or subcloning genes which are unstable and/or toxic in high-copy-number vectors.

Aggregatibacter actinomycetemcomitans↗

Tyrosine protein phosphorylation in murine B lymphocytes by stimulation with lipopolysaccharide from Porphyromonas gingivalis.

The molecular effect of lipopolysaccharides (LPS) from porphyromonas gingivalis as well as Escherichia coli on the tyrosine protein phosphorylation in the splenic B lymphocytes from LPS-responsive C3H/HeN and LPS-hyporesponsive C3H/HeJ mice was examined. P. gingivalis LPS induced tyrosine phosphorylation of selected membrane proteins that included the phosphoproteins with apparent molecular masses of 24.8 kDa and 26.0 kDa (p24.8 and p26.) in the B lymphocytes from both strains of mice, while E. coli LPS induced p24.8 and p26.0 in C3H/HeN B Lymphocytes only. These findings suggest that through the same tyrosine phosphorylation pathway as observed in C3H/HeN B lymphocytes, P. gingivalis LPS induced the activation of C3H/HeJ B lymphocytes in which a trigger signal by E. coli LPS could not be transduced to initiate tyrosine protein phosphorylation.

Animals↗

Stimulation of glossopharyngeal and laryngeal nerve afferents induces expulsion only when it is applied during retching in paralyzed decerebrate dogs.

Stimulation of the oropharyngeal mucosa induces vomiting in humans, however, it has not been seen in animals. Thus, we attempted to induce fictive vomiting by stimulation of lingual and pharyngeal branch afferents of the glossopharyngeal nerve, and afferents of the superior and recurrent laryngeal nerves in paralyzed decerebrate dogs. The stimulation did not induce fictive vomiting when it was applied during eupnea, but induced fictive expulsion when it was applied during fictive retching. Threshold intensity for the induction decreased with the progress of retching.

Afferent Pathways↗

D-myo-inositol 1,4,5-trisphosphate analogues substituted at the 3-hydroxyl group.

D-myo-Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) analogues derived at 3-OH with a bulky substituent were chemically synthesized and structural features of vicinity surrounding the 3-OH of Ins(1,4,5)P3, recognized by metabolic enzymes and by the receptor were explored. 3-Benzoyl-, 3-methylbenzoyl- and 3-para-aminobenzoyl-Ins(1,4,5)P3 inhibited the dephosphorylation of [3H]Ins(1,4,5)P3 by the 5-phosphatase present in erythrocyte ghosts, but the potency varied. The inhibitory potency for the former two compounds was slightly lower than that for Ins(1,4,5)P3, while that for the latter compound was higher. Transfer of the amino group to the meta-position of the benzoyl group led to a less potent analogue. In an assay of [3H]Ins(1,4,5)P3 3-kinase at a low Ca2+ concentration, catalyzed by rat brain cytosol, 3-meta-aminobenzoyl-Ins(1,4,5)P3 was the most potent among compounds examined, including Ins(1,4,5)P3 in inhibiting the phosphorylation, whereas both 3-benzoyl- and 3-methylbenzoyl-Ins(1,4,5)P3 at concentrations up to 30 microM, were without effect. All analogues examined were effective in inhibiting [3H]Ins(1,4,5)P3 binding to purified Ins(1,4,5)P3 receptor, but all 3-derived analogues were less potent and 3-benzoyl-Ins(1,4,5)P3 was the least potent. It would thus appear that the space in the vicinity surrounding the 3-hydroxyl group of Ins(1,4,5)P3 is sterically restrictive with regard to recognition by metabolic enzymes and the receptor, whereas the amino group providing arms for either the electrostatic interaction or the hydrogen bond, makes the analogues more potent.

Calcium Channels↗

Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits.

The generation of secretory IgA Abs for specific immune protection of mucosal surfaces depends on stimulation of the mucosal immune system, but this is not effectively achieved by parenteral or even oral administration of most soluble Ags. To harness the exceptional mucosal immunogenicity of cholera toxin (CT), which is largely attributed to the cell-binding property of its B subunit, for the generation of other oral vaccines, we have genetically replaced the toxic A1 subunit of CT with a 42-kDa segment of a streptococcal protein adhesin. This construct was expressed in Escherichia coli as a chimeric protein that retained the GM1 ganglioside-binding activity of CT subunit B and the antigenicity of the streptococcal adhesin, as shown by GM1-ELISA developed with Abs to the steptococcal segment. The protein composition of chromatographically purified chimeric protein was verified by SDS-PAGE and Western blotting with Abs to both antigenic components of the construct. Peroral administration of this chimeric immunogen in mice elicited high levels of mucosal IgA and serum IgG Abs to the streptococcal adhesin, which persisted for at least 6 mo. This strategy allows the development of similar constructs from other candidate Ags for oral immunization against a variety of mucosally acquired infections.

Adhesins, Bacterial↗

Effects of randomization of partially hydrogenated corn oil on fatty acid and cholesterol absorption, and tissue lipid levels in rats.

Randomization of partially hydrogenated corn oil containing approximately 45% of trans octadecenoic acid only slightly, but not significantly, increased the lymphatic fatty acid absorption in rats. No effect of randomization was observed on cholesterol absorption. When rats were fed these fats at the 8.8% level (with 1.2% safflower oil) for three weeks, the concentrations of serum cholesterol, and serum and liver phospholipid were significantly higher in randomized fat than in control fat, which was composed of 9% high-oleic safflower oil and 1% palm oil. Liver cholesterol tended to be higher in randomized fat. In contrast, nonrandomized fat was not hyperlipidemic compared to control fat. Although the fatty acid composition of liver phospholipids suggested a possible interference of trans fatty acid with the metabolism of linoleic acid to arachidonic acid, there was no effect of randomization. In the two hydrogenated fat groups, trans octadecenoic acid was incorporated and distributed similarly in adipose tissue triacylglycerol. These observations indicated that randomization of partially hydrogenated fat is not beneficial to various lipid parameters in rats.

Absorption↗

Tissue-selective inhibition of sterol synthesis in mice by pravastatin sodium after a single or repeated oral administrations.

Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, exhibits liver-selectivity in inhibiting sterol synthesis, when administered as a single oral dose to mice or rats, whereas lovastatin and simvastatin do not. This may be due to the fact that pravastatin is distributed intracellularly, to a large extent, in the liver and extracellularly in nonhepatic tissues. In the present study, we examined whether the difference in liver-selectivity among these three HMG-CoA reductase inhibitors observed in single-dose studies was preserved after repeated oral administrations of drugs to mice. De novo sterol synthesis in different tissues of mice was examined in vivo three hours after the last dose of drug by measuring incorporation of intraperitoneally injected [14C]acetate into total sterols. Pravastatin administered orally for 11 consecutive days at 5 and 10 mg/kg exhibited a greater liver-selectivity than lovastatin and simvastatin: sterol synthesis was inhibited more than 60% in the liver by all three drugs, whereas that in nonhepatic tissues was inhibited less than 10% by pravastatin and more than 30% by lovastatin and simvastatinin in most of the nonhepatic tissues examined. Pravastatin administered orally for 11 consecutive days at 10 mg/kg caused more selective inhibition of sterol synthesis in liver ex vivo than two other inhibitors at the same dose. Pravastatin inhibited de novo sterol synthesis from [14C]acetate into sterol fraction in the liver slices in vitro, but minimally in those of the spleen and testis, whereas lovastatin and simvastatin inhibited in those of all three tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Activation of peripheral and/or central chemoreceptors changes retching activities of Bötzinger complex neurons and induces expulsion in decerebrate dogs.

Fictive expulsion can be induced by electrical stimulation of the carotid sinus nerve during fictive retching or by discontinuing artificial ventilation in decerebrate paralyzed dogs. Both the phrenic and abdominal muscle nerves discharge during the early phase of fictive expulsion, but only the abdominal muscle nerve continues to discharge during the late phase. To determine whether Bötzinger complex (BOT) neurons participate in expulsion, responses to sinus nerve stimulation were examined in 47 non-respiratory (N-RES), 15 inspiratory (INS) and 12 expiratory (EXP) BOT neurons during eupnea. About 80% of the neurons produced excitatory or inhibitory responses. FIring patterns were observed in 61 N-RES, 39 INS and 56 EXP BOT neurons during expulsion induced by sinus nerve stimulation or by discontinuation of artificial ventilation. An activity pattern similar to that of the phrenic nerve was exhibited during fictive retching and expulsions by 13 N-RES< 3 INS and 8 EXP neurons, and a firing pattern like that of the abdominal muscle nerve was produced by 11 N-RES, 6 INS and 5 EXP neurons. Bursts were limited to the late phase of expulsion and to the period just after expulsion in 5 N-RES, 3 INS and 3 EXP neurons, and in 8 N-RES and 21 EXP neurons, respectively. Firings of the two latter groups of neurons decreased concomitantly with each retch or during retching. These results suggest that neurons of the two latter groups play crucial roles in the central patterning of neuronal expulsion activities.

Animals↗

Case report: cheilitis granulomatosa with periodontitis.

We report a case of cheilitis granulomatosa with periodontitis in a 39-year-old Japanese man. Biopsy specimens from both areas showed noncaseating epithelioid cell granuloma. Dental examination revealed that the lower left first molar had periodontitis. The lower left first molar was removed, and antibiotics and anti-inflammatory drugs were administered. After 2 months of periodontitis therapy, the lips returned to normal size without recurrence and the swelling of the buccal mucosa regressed.

Adult↗