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Biomedical subjects

K Tai

Publications and source records attributed to K Tai.

At least 19 recordsLinked to original sources
PubMed2004

Nucleotide sequence analysis of the recA gene and discrimination of the three isolates of urease-positive thermophilic Campylobacter (UPTC) isolated from seagulls (Larus spp.) in Northern Ireland.

Nucleotide sequencing after TA cloning of the amplicon of the almost-full length recA gene from three strains of UPTC (A1, A2, and A3) isolated from seagulls in Northern Ireland, the phenotypical and genotypical characteristics of which have been demonstrated to be indistinguishable, clarified nucleotide differences at three nucleotide positions among the three strains. In conclusion, the nucleotide sequences of the recA gene were found to discriminate among the three strains of UPTC, A1, A2, and A3, which are indistinguishable phenotypically and genotypically. Thus, the present study strongly suggests that nucleotide sequence data of the amplicon of a suitable gene or region could aid in discriminating among isolates of the UPTC group, which are indistinguishable phenotypically and genotypically.

Animals↗
PubMed2001

Cross-talk between IL-1 and IL-6 signaling pathways in rheumatoid arthritis synovial fibroblasts.

The balance between pro- and anti-inflammatory cytokines plays an important role in determining the severity of inflammation in rheumatoid arthritis (RA). Antagonism between opposing cytokines at the level of signal transduction plays an important role in many other systems. We have begun to explore the possible contribution of signal transduction cross-talk to cytokine balance in RA by examining the effects of IL-1, a proinflammatory cytokine, on the signaling and action of IL-6, a pleiotropic cytokine that has both pro- and anti-inflammatory actions, in RA synovial fibroblasts. Pretreatment with IL-1 suppressed Janus kinase-STAT signaling by IL-6, modified patterns of gene activation, and blocked IL-6 induction of tissue inhibitor of metalloproteases 1 expression. These results suggest that proinflammatory cytokines may contribute to pathogenesis by modulating or blocking signal transduction by pleiotropic or anti-inflammatory cytokines. The mechanism of inhibition did not require de novo gene activation and did not depend upon tyrosine phosphatase activity, but, instead, was dependent on the p38 stress kinase. These results identify a molecular basis for IL-1 and IL-6 cross-talk in RA synoviocytes and suggest that, in addition to levels of cytokine expression, modulation of signal transduction also plays a role in regulating cytokine balance in RA.

Arthritis, Rheumatoid↗
PubMed2001

Statistical analysis of the fractal gating motions of the enzyme acetylcholinesterase.

The enzyme acetylcholinesterase has an active site that is accessible only by a "gorge" or main channel from the surface, and perhaps by secondary channels such as the "back door." Molecular-dynamics simulations show that these channels are too narrow most of the time to admit substrate or other small molecules. Binding of substrates is therefore "gated" by structural fluctuations of the enzyme. Here, we analyze the fluctuations of these possible channels, as observed in the 10.8-ns trajectory of the simulation. The probability density function of the gorge proper radius (defined in the text) was calculated. A double-peak feature of the function was discovered and therefore two states with a threshold were identified. The relaxation (transition probability) functions of these two states were also calculated. The results revealed a power-law decay trend and an oscillation around it, which show properties of fractal dynamics with a "complex exponent." The cross correlation of potential energy versus proper radius was also investigated. We discuss possible physical models behind the fractal protein dynamics; the dynamic hierarchical model for glassy systems is evaluated in detail.

Acetylcholinesterase↗
PubMed2001

Analysis of a 10-ns molecular dynamics simulation of mouse acetylcholinesterase.

A 10-ns molecular dynamics simulation of mouse acetylcholinesterase was analyzed, with special attention paid to the fluctuation in the width of the gorge and opening events of the back door. The trajectory was first verified to ensure its stability. We defined the gorge proper radius as the measure for the extent of gorge opening. We developed an expression of an inter-atom distance representative of the gorge proper radius in terms of projections on the principal components. This revealed the fact that collective motions of many scales contribute to the opening behavior of the gorge. Covariance and correlation results identified the motions of the protein backbone as the gorge opens. In the back-door region, side-chain dihedral angles that define the opening were identified.

Acetylcholinesterase↗
PubMed2001

Existence of retinoic acid-receptor-independent retinoid X-receptor-dependent pathway in myeloid cell function.

We previously reported that ER-27191 (4-[4,5,7,8,9,10-hexahydro-7,7,10,10-tetramethyl-1-(3-pyridylmethyl)anthra[1,2-b]pyrrol-3-yl]benzoic acid) is a potent antagonist of retinoic acid receptor (RAR), and ER-35795 ((2E,4E,6E)-7-[1-(1-methylethyl)-8-chloro-1,2,3,4-tetrahydroquinolin-6-yl]-6-fluoro-3-methyl-2,4,6-nonatrienoic acid) is a novel retinoid X receptor (RXR)-specific agonist. By using these compounds, we investigated whether distinct RAR-dependent and RXR-dependent pathways operate to mediate the diverse activities of retinoids, particularly, the effects of the RXR pathway on cellular function. ER-27191 completely antagonized HL60 cell differentiation induced by all-trans-retinoic acid (atRA). However, the differentiation induced by the ER-35795 was not antagonized at all by the RAR antagonist, but was inhibited by an RXR homodimer antagonist (LGD100754, (2E,4E,6Z)-7-(3-n-propoxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)-3-methylocta-2,4,6-trienoic acid). Its agonistic action on RXR/RAR heterodimer, on the other hand, was neutralized by the RAR antagonist. During HL60 cell differentiation, atRA induced RARbeta mRNA, while the RXR had no effect. Interestingly, a functional RXR-pathway was also seen in lipopolysaccharide-induced inhibition of mouse splenocyte proliferation. These results strongly suggest the existence of a pharmacological RXR-dependent pathway that is activated by a ligand that can bind to RXR.

Animals↗
PubMed2000

Discovery of novel and potent retinoic acid receptor alpha agonists: syntheses and evaluation of benzofuranyl-pyrrole and benzothiophenyl-pyrrole derivatives.

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of benzofuran and benzothiophene derivatives. Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte proliferation and exerted RARalpha selectivity. One of them, 4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered significantly inhibited mouse antibody production and delayed type hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.

Administration, Oral↗
PubMed2000

Novel retinoic acid receptor alpha agonists: syntheses and evaluation of pyrazole derivatives.

We have designed and synthesized a series of pyrazole derivatives as candidate retinoic acid receptor (RAR) agonists. One of them, 4-[5-(1, 5-diisopropyl-1H-3-pyrazolyl)-1H-2-pyrrolyl]benzoic acid (11b), which possesses a 2,5-disubstituted pyrrole moiety, showed selective transactivation activity for the RAR alpha receptor, and had highly potent cell-differentiating activity on HL-60 cells.

Binding, Competitive↗
PubMed2000

Syntheses and structure-activity relationships of 5,6,7, 8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity.

In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of quinoxaline derivatives. One of them, 4-[5-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-quinoxalinyl)-1H-2-pyrrolyl]benzoic acid (3a), which possesses a 2,5-disubstituted pyrrole moiety, showed selectivity for the RARalpha receptor and exerted highly potent cell-differentiating activity on HL-60 cells.

Benzoates↗
PubMed2000

[Preoperative questionnaire survey about anxiety of patients for scheduled operation].

Preoperative patients have various kinds of anxiety. However we do not know much about their psychological burden. Therefore, we investigated types of their anxiety with questionnaires prior to operation and analyzed them according to their anesthetic method, type of surgery and age. Concerning anesthetic methods, patients' anxiety varied depending on their histories of anesthesia, anesthetic method previously received and age. Concerning the type of surgery, patients scheduled to undergo abdominal and cardiac surgery had more intense anxiety. Patients scheduled for gynecological surgery were anxious about the accident which might be induced by anesthesia. A large number of patients scheduled for orthopedic surgery were anxious about postoperative pain. Concerning patients' age, patients whose ages ranged from 10s to 50s were anxious about pain. While, in patients over 60s, their anxiety was focussed on giving trouble to their surrounding people. Patients whose age was 10 to 19 had anxiety about their anesthetic method. Anesthesiologists should recognize that preoperative patients have various kinds of anxiety. It is important for us to examine the patients appropriately according to their psychological and physical condition.

Adolescent↗
PubMed1998

Plasmodium falciparum produces prostaglandins that are pyrogenic, somnogenic, and immunosuppressive substances in humans.

Plasmodium falciparum causes the most severe form of human malaria, which kills approximately 1.5-2.7 million people every year, but the molecular mechanisms underlying the clinical symptoms and the host-parasite interaction remain unclear. We show here that P. falciparum produces prostaglandins (PGs) D2, E2, and F2alpha. After incubation with 1 mM arachidonic acid (AA), cell homogenates of P. falciparum produced PGs as determined by enzyme immunoassay and gas chromatography-selected ion monitoring. PG production in the parasite homogenate was not affected by the nonsteroidal antiinflammatory drugs aspirin and indomethacin, and was partially heat resistant, whereas PG biosynthesis by mammalian cyclooxygenase was completely inhibited by these chemicals and by heat treatment. Addition of AA to the parasite cell culture markedly increased an ability of the parasite cell homogenate to produce PGs and of parasitized red blood cells to accumulate PGs in the culture medium. PGD2 and PGE2 accumulated in the culture medium at the stages of trophozoites and schizonts more actively than at the ring stage. These findings are the first evidence of the direct involvement of a malaria parasite in the generation of substances that are pyrogenic and injurious to the host defenses. We will discuss a possible contribution of the parasite-produced PGs to pathogenesis and host-parasite interaction of P. falciparum.

Animals↗
PubMed1998

Syntheses and structure-activity relationships of novel retinoid X receptor agonists.

As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, generated by introducing a polar N atom into the hydrophobic part of the retinoid skeleton, showed high binding affinity to RXRs. Addition of fluorine at the 6-position of the 2,4,6-trienoic acid moiety afforded compounds which elicit potent and selective transactivation of the RXRs. Compound 14b (ER-35794), which possesses an ethyl substituent at the 7-position and fluorine at the 6-position of the triene moiety, is one of the most potent and selective RXR agonists reported to date.

Animals↗
PubMed1996

Production of recombinant SERA proteins of Plasmodium falciparum in Escherichia coli by using synthetic genes.

We expressed two regions of the serine repeat antigen (SERA) protein of Plasmodium falciparum in Escherichia coli by synthesizing the genes with a changed codon usage. One of the synthetic gene sequences encodes amino acid residues 17-382 (SE47') and the other encodes amino acid residues 586-802 (SE50A). The products produced by the synthetic gene sequences in E. coli accounted for 15-30% of the total bacterial protein. Antisera against both the purified gene products prepared in rats inhibited malaria parasite growth in vitro. The anti-SE47' serum was significantly more inhibitory than the anti-SE50A serum. The described methods provide a large scale preparation of recombinant antigens for improving and producing malaria vaccine.

Amino Acid Sequence↗