Search PubMed⌕ Search

Biomedical subjects

Y Maki

Publications and source records attributed to Y Maki.

At least 19 recordsLinked to original sources

Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition.

The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid. In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.

Amino Acids, Essential↗

Increased susceptibility to apoptosis in CD45(+) myeloma cells accompanied by the increased expression of VDAC1.

Expression of CD45 is quite variable in human myeloma cells and cell lines, such as U266, and CD45(+) U266 proliferates in response to a growth factor, interleukin-6. Here, we show that CD45(+) myeloma cell lines were more sensitive to various apoptotic stimuli, such as oxidative stress and endoplasmic reticulum (ER)-stress, than CD45(-) cells. Reactive oxygen species and calcium ion seemed to be involved in the susceptibility to apoptosis of CD45(+) U266. The activation of the src family kinases associated with CD45 phosphatase played an important role in the augmented apoptosis in CD45(+) U266 by oxidative stress. These results indicate that the CD45-expression renders myeloma cells competent for not only mitogenic but also apoptotic stimuli, resulting in either proliferation or apoptosis of CD45(+) myeloma cells dependently upon the circumstantial stimuli. Furthermore, voltage-dependent anion channel (VDAC) 1 was identified as a gene highly expressed in CD45(+) U266 by cDNA subtraction. The increased expression of VDAC1 seemed to augment the sensitivity to the ER-stress because the VDAC1-transfected U266 was more susceptible to the thapsigargin-induced apoptosis. Thus, CD45 expression accompanied by the increased VDAC1 expression sensitizes myeloma cells to the various extracellular stimuli that trigger apoptosis via the mitochondrial pathways.

Apoptosis↗

A rapid and quantitative detection system for Streptococcus mutans in saliva using monoclonal antibodies.

A new semiquantitative enumeration system was developed to detect Streptococcus mutans in saliva. Using species-specific monoclonal antibodies, the system quickly detected salivary S. mutans in 30 min and classified the results into three levels. In this study, saliva samples collected from 28 young adults aged between 22 and 24 years were subjected to the monoclonal antibody-based detecting system and selective medium-based detecting methods. The results generated from the PCR-confirmed culture method indicated the mean salivary S. mutans counts at level 1, 2 and 3 were 5.7 x 10(4), 1.3 x 10(5) and 3.4 x 10(6) CFU/ml, respectively. The differences between level 3 and 1 and level 3 and 2 were statistically significant (one-way ANOVA; p < 0.01). The results generated from the system were consistent with the data generated from two culture-based commercial products.

Adult↗

Toxoplasma gondii antigens GRA1 (p24) and SAG1 (p30): a comparison of their stimulatory influence on T-cell activation and cytokine expression in in vitro cultures.

The influence of recombinant cell surface SAG1 (rp30) and secretory GRA1 (rp24) antigens (Ag) on T-cell activation and cytokine induction in vitro was compared. T-cell activity and the level of IFN-gamma, IL-10 and IL-12 expression in rp30-immunized T cells were considerably increased in the presence of rp30 Ags. IgG2a and IgG1 antibodies (Ab) were detected in sera of rp24- and rp30-immunized mice, with the secretory rp24 Ag having induced significantly higher titer of IgG1 Ab. In vitro, the greater antigenicity of surface rp30 Ag was notable based on the level of T-cell activation, and cytokine synthesis suggestive of the participation of Th1 cells. Although, IFN-gamma expression by rp24 Ag was lower compared to rp30 Ag, the synthesis of both IgG2a and IgG1 Abs reflects the protective nature of rp24 Ag. We have generated two recombinant Toxoplasma gondii Ags that demonstrated differences in antigenicity in vitro. It would be interesting to evaluate the mechanism(s) of immunity induced by SAG1 (p30) and GRA1 (p24) Ags against infection with T. gondii in vivo.

Adenosine Triphosphate↗

Salivary flow and its relationship to oral signs and symptoms in patients with dry eyes.

OBJECTIVES: The aim of this study was to investigate oral symptoms and clinical parameters in dry eye patients. Subjective reports of the sensation of a dry mouth, salivary flow rates, and clinical parameters of oral disease related to three different types of dry eye patients were examined. SUBJECTS AND METHODS: There were 224 individuals, including dry eye patients and control subjects. The dry eye patients were classified into three types: patients with Sjögren's syndrome (SS-DE), patients without SS-DE (non-SS-DE), and patients with Stevens-Johnson syndrome (SJS-DE). Salivary flow rates were measured using two kinds of sialometry. Subjective and objective oral symptoms and signs were also examined. RESULTS AND CONCLUSION: Over half of the dry eye patients complained of a dry mouth. The flow rates of their stimulated whole saliva and parotid saliva were significantly lower than those of the control groups (P < 0.05, P < 0.01). The sensation of a dry mouth and changes in oral soft tissues, dental caries, and oral Candida frequently occurred in dry eye patients.

Adult↗

Artificial substrates of medium-chain elongating enzymes, hexaprenyl- and heptaprenyl diphosphate synthases.

We examined the reactivity of 3-alkyl group homologues of farnesyl diphosphate or isopentenyl diphosphate for medium-chain prenyl diphosphate synthases, hexaprenyl diphosphate- or heptaprenyl diphosphate synthase. But-3-enyl diphosphate, which lacks the methyl group at the 3-position of isopentenyl diphosphate, condensed only once with farnesyl diphosphate to give E-norgeranylgeranyl diphosphate by the action of either enzyme. However, norfarnesyl diphosphate was never accepted as an allylic substrate at all. 3-Ethylbut-3-enyl diphosphate also reacted with farnesyl diphosphate giving a mixture of (all-E)-3-ethyl-7,11,15-trimethylhexadeca-2,6,10,14-tetraenyl- and (all-E)-3,7-diethyl-11,15,19-trimethylicosa-2,6,10,14,18-pentaenyl diphosphates by hexaprenyl diphosphate synthase. On the other hand, heptaprenyl diphosphate synthase reaction of 3-ethylbut-3-enyl diphosphate with farnesyl diphosphate gave only (all-E)-3-ethyl-7,11,15-trimethylhexadeca-2,6,10,14-tetraenyl diphosphate.

Alkyl and Aryl Transferases↗

Development of a system for the inference of large scale genetic networks.

We propose a system named AIGNET (Algorithms for Inference of Genetic Networks), and introduce two top-down approaches for the inference of interrelated mechanism among genes in genetic network that is based on the steady state and temporal analyses of gene expression patterns against some kinds of gene perturbations such as disruption or overexpression. The former analysis is performed by a static Boolean network model based on multi-level digraph, and the latter one is by S-system model. By integrating these two analyses, we show our strategy is flexible and rich in structure to treat gene expression patterns; we applied our strategy to the inference of a genetic network that is composed of 30 genes as a case study. Given the gene expression time-course data set under the conditions of wild-type and the deletion of one gene, our system enabled us to reconstruct the same network architecture as original one.

Algorithms↗

Optimal starting time for flutamide to prevent disease flare in prostate cancer patients treated with a gonadotropin-releasing hormone agonist.

OBJECTIVE: Flare-up phenomena, such as an increase in prostate-specific antigen (PSA) and/or deterioration of symptoms, are observed in some patients undergoing gonadotropin-releasing hormone (GnRH) agonist therapy. This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena. PATIENTS AND METHODS: Twenty-six patients with prostate cancer and elevated serum levels of PSA were randomly assigned to 5 groups. Group A patients (n = 6) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone. Group B, C, D and E patients (5 patients in each group) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin. Flutamide was initiated on the day of leuprorelin injection in group B, and at 1, 2 and 4 weeks before leuprorelin injection in groups C, D and E, respectively. Serum PSA and testosterone levels were measured in each patient. RESULTS: Pretreatment with flutamide increased the serum testosterone level, but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups. In patients who had been treated with flutamide in combination with leuprorelin, the mean PSA level did not exceed the pretreatment levels after leuprorelin administration. The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups. CONCLUSION: Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena.

Adenocarcinoma↗

Competitive amino acid transport between L-tryptophan and other amino acids in Schizophyllum commune.

In our study on nutritional requirement for the hyphal growth of Schizophyllum commune, we found that a Trp- mutant could not grow in the L-Trp-supplied medium in the presence of L-Ser. Further growth studies showed that not only L-Ser but also as many as 11 kinds of amino acid including L-Ala, L-Arg, L-Asn, L-His, L-Leu, L-Met, L-Phe, L-Ser, L-Thr, L-Tyr and L-Val inhibited the growth of the Trp- mutant in the L-Trp-supplied medium. However, these amino acids did not inhibit the growth of a Trp+ strain. The inhibition of growth of Trp+ strain induced by a Trp analogue of 5-fluoro-DL-tryptophan (5FT), which was usually recovered by L-Trp, was rescued by the same amino acids mentioned above. The exceptions were Gly and L-Ile, which also recovered the growth inhibition induced by 5FT. These results indicate that the permease responsible for the Trp transport in S. commune might also be active to other amino acids. However, it is considered that the permease shows high affinity to L-Trp and low affinity to other amino acids. As a result, the transport of L-Trp and 5FT may be counteracted by other amino acids.

Journal Article↗

[Early phase II study of amrubicin (SM-5887) for superficial bladder cancer: a dose-finding study for intravesical chemotherapy].

An early phase II study (dose-finding study) of amrubicin hydrochloride for superficial bladder cancer was conducted. Amrubicin was dissolved in 30 ml of physiological saline and injected intravesically for 6 consecutive days. The drug solution was retained for 2 hours. Patients were randomly assigned to four groups, which were administered amrubicin at doses of 30, 60, 90, and 120 mg/day, respectively. Of 65 patients registered in this study, 63 were eligible and assessable for toxicities, and 55 assessable for efficacy. The response rate at each dose level was 50.0% (7PRs/14 patients) at 30 mg/day, 53.3% (8 PRs/15) at 60 mg/day, 61.5% (2 CRs + 6 PRs/13) at 90 mg/day, and 69.2% (2 CRs + 7 PRs/13) at 120 mg/day, respectively. These data suggests that the efficacy was related to the doses of amrubicin. The major toxicities were cystic irritabilities, such as micturition pain, pollakisuria and hematuria. These toxicities were related to the doses of amrubicin. Their incidence and the severity were not high compared with those reported about other anthracyclines such as doxorubicin and epirubicin. The optimal dose of amrubicin was estimated to be 90 to 120 mg/day in the intravesical treatment for superficial bladder cancer once a day for 6 consecutive days.

Administration, Intravesical↗

[A behavioral and neurochemical study on the mechanism of the anxiolytic effect of monoamine oxidase inhibitors].

The author examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety, induced by conditioned fear stress. The selective serotonin1A receptor agonist inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), Ro 41-1049 (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects. These results suggest that acute inhibition of both monoamine oxidase A and B reduces anxiety or fear, while inhibition of monoamine oxidase A or B alone fails to reduce anxiety or fear. In vivo microdialysis studies showed that the irreversible monoamine oxidase A inhibitor clorgyline and the irreversible monoamine oxidase B inhibitor selegiline induced a mild increase and no increase in extracellular serotonin, respectively. Interestingly, the combined treatment with clorgyline and selegiline resulted in much larger increases in extracellular serotonin in the medial prefrontal cortex than did either monoamine oxidase inhibitor alone. Our previous studies have indicated that facilitation of 5-HT neurotransmission decreases conditioned freezing, i.e., anxiety or fear. The results of these in vivo microdialysis studies may account for the results of this study that the simultaneous blockade of both monoamine oxidase A and B reduced conditioned freezing, whereas blockade of either monoamine oxidase alone failed.

Animals↗

Monoamine oxidase inhibitors reduce conditioned fear stress-induced freezing behavior in rats.

The present study examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety induced by conditioned fear stress. The selective serotonin 1A receptor agonist tandospirone (0.1-10 mg/kg) inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide (Ro 41-1049) (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects. These results suggest that acute inhibition of both monoamine oxidase A and B reduced anxiety or fear, while inhibition of monoamine oxidase A or B alone failed to reduce anxiety or fear.

Animals↗

Tumor metastasis-associated human MTA1 gene: its deduced protein sequence, localization, and association with breast cancer cell proliferation using antisense phosphorothioate oligonucleotides.

Using differential cDNA library screening techniques based on metastatic and nonmetastatic rat mammary adenocarcinoma cell lines we previously cloned and sequenced the metastasis-associated gene mta1. Using homology to the rat MTA1 gene we cloned the human MTA1 gene and found it to be overexpressed in a variety of human cell lines. We found a close similarity between the human MTA1 and rat MTA1 genes, as shown by 88% and 96% identities of the nucleotide and predicted amino acid sequences, respectively. Both genes encode novel proteins that contain a proline-rich region (SH3 binding motif), a putative zinc finger motif, a leucine zipper motif, and five copies of the SPXX motif often found in gene regulatory proteins. Using Southern blot analysis, the MTA1 gene was found to be highly conserved among all species examined; and using Northern blot analysis, MTA1 transcripts were found in virtually all cell lines of human origin that were analyzed, including melanoma and breast, cervix and ovarian carcinoma cells and normal breast epithelial cells. However, the expression level of the MTA1 gene in a normal breast epithelial cell was approximately 50% of that found in rapidly growing breast adenocarcinoma cell lines and an atypical mammary cell line. Experimental inhibition of MTA1 protein expression using antisense phosphorothioate oligonucleotides resulted in growth inhibition of human MDA-MB-231 breast cancer cells with relatively high expression of the MTA1 gene. Furthermore, the MTA1 protein was localized in the nuclei of cells transfected using a mammalian expression vector containing the full-length MTA1 gene. The results suggest that the MTA1 protein may function in cellular signaling processes important in the progression and growth of cancer cells, possibly as a nuclear regulatory factor.

Amino Acid Sequence↗

Molecular cloning and characterization of a rice dehydroascorbate reductase.

Plant dehydroascorbate reductase (DHAR), which re-reduces oxidized ascorbate to maintain an appropriate level of ascorbate, is very important, but no gene or cDNA for plant DHAR has been cloned yet. Here, we describe a cDNA for a rice glutathione-dependent DHAR (designated DHAR1). A recombinant Dhar1p produced in Escherichia coli was functional. The expression sequence tag database suggests that Dhar1p homologs exist in various plants. Furthermore, the rice Dhar1p has a low similarity to rat DHAR, although the rice enzyme has a considerably higher specific activity than the mammalian one. The mRNA level of DHAR1, the protein level of Dhar1p and the DHAR activity in rice seedlings were elevated by high temperature, suggesting the protection role of DHAR at high temperature.

Amino Acid Sequence↗

Expression of SAG-1 of Toxoplasma gondii in transgenic mice.

We describe the expression of SAG-1 cDNA in B6C3F1 mice by microinjecting a 3.3 kbp DNA fragment, consisting of the cytomegalovirus enhancer-chicken beta-actin hybrid promoter and SAG-1 into the pronucleus of a fertilized egg at the one-cell stage. Offspring derived from this microinjection were analyzed for the integration and functional expression of the SAG-1 transgene. Steady-state expressions of both the mRNA for SAG-1 and SAG-1 protein product were detected in the brain, thymus, spleen and liver. Approximately 50% of F1 and F2 progeny inherited the SAG-1 transgene from SAG-1 transgenic mice in Mendelian fashion. These results indicated that SAG-1 transgenic lines were established. Transgenic mice harboring the SAG-1 gene will contribute a critical tool of defining the molecular mechanisms of SAG-1 in pathogenesis and host immune response.

3T3 Cells↗

Effect of the dopamine D(1/5) antagonist SCH 23390 on the acquisition of conditioned fear.

The authors previously reported that typical and atypical antipsychotic drugs inhibited the acquisition but not expression of conditioned fear. The present study examined the effects of the selective dopamine D(1/5) agonist (SKF 38393) and antagonist (SCH 23390) on the acquisition and expression of conditioned fear. Drugs were administered subcutaneously to male Sprague-Dawley rats 30 min before foot shock (2.5 mA for 5 min). Twenty-four hours after foot shock, rats were again placed and observed in the shock chamber without shocks (conditioned fear). Freezing behavior induced by conditioned fear, an index of anxiety or fear, was recorded using a time-sampling procedure. SCH 23390 (0.1-1 mg/kg) inhibited the acquisition of conditioned freezing. The administration of SCH 23390 at a dose of 0.1 mg/kg 30 min after foot shock did not affect conditioned freezing. Taken together, it is concluded that D(1/5) antagonism inhibits the acquisition of conditioned fear. SKF 38393 (3-20 mg/kg) failed to change the acquisition of conditioned fear. SCH 23390 or SKF 38393 administered prior to testing did not reduce the expression of conditioned fear. These results suggest that D(1/5) receptors may play a role in the development of fear or anxiety.

Animals↗

Two proteins, YfiA and YhbH, associated with resting ribosomes in stationary phase Escherichia coli.

BACKGROUND: Ribosomes in Escherichia coli change their composition and conformation in the stationary phase. Ribosome modulation factor (RMF) and ribosomal protein S22 are known to be associated with stationary phase ribosomes. RMF association causes the loss of translational activity and the dimerization of 70S ribosomes into 100S ribosomes, which may increase cell survival in the stationary phase. RESULTS: Two weakly acidic proteins having related amino acid sequences were found to be associated with E. coli ribosomes in the stationary phase. These proteins are the products of ORFs named yfiA and yhbH. The sum of the copy numbers of their product proteins, YfiA and YhbH, in the ribosomal particles was low in the log phase, but increased to nearly one in the stationary phase. YfiA was found in the 70S ribosomal fraction rather than the 100S. On the other hand, YhbH was detected exclusively in the 100S ribosomal fraction. When the stationary phase cells were transferred to fresh medium, YfiA and YhbH were found in the 70S ribosomal fraction, but not in the polysome fraction. CONCLUSIONS: Two proteins, YfiA and YhbH, associated with E. coli ribosomes were found to accumulate in the stationary phase, leading to the formation of several types of ribosomes. They are not likely to have roles in the elongation step of the translation in log phase cells, but are likely to be involved in the stabilization and preservation of ribosomes in the stationary phase, which might be necessary for cell survival.

Amino Acid Sequence↗