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Biomedical subjects

N Sugimoto

Publications and source records attributed to N Sugimoto.

At least 55 records · Page 3Linked to original sources
PubMed2000

Differential effects of N-acetyl-l-cysteine on IL-2- vs IL-12-driven proliferation of a T cell clone: implications for distinct signalling pathways.

Using a T cell clone (2D6) capable of responding to IL-2 and IL-12, we compared the effects of NAC on IL-2 and IL-12-driven T cell proliferation. Addition of N-acetylcysteine (NAC) to 2D6 cultures did not affect IL-2 stimulated proliferation, but strikingly inhibited IL-12 stimulated proliferation. These differential NAC effects did not correlate with the patterns of the mitogen-activated protein kinase (MAPK) activation following cytokine stimulation and its regulation by NAC. Although a p38 MAPK inhibitor downregulated both IL-2- and IL-12-induced proliferation, this effect was seen at drug concentrations one order higher than those reportedly used to specifically inhibit p38 MAPK. The results suggest the existence of distinct signalling pathways and a common, indispensable signalling molecule in IL-2- and IL-12 driven T cell proliferation.

Acetylcysteine↗
PubMed2000

Changes in ambient temperature at the onset of thermoregulatory responses in exercise-trained rats.

Spontaneous running in a wheel has emerged as a useful method of exercise in rodents. We investigated how exercise training with a running wheel affects ambient temperatures (T(a)) at the onset of thermoregulatory responses in rats. Female rats were allowed to run freely in the wheel for 6 months. Sedentary control rats did not exercise during the same period. After the exercise training period, they were loosely restrained and T(a) values at the onset of tail skin vasodilation and cold-induced thermogenesis were determined by raising or lowering T(a). Resting levels of core temperature and heat production of the exercise-trained rats were significantly higher than those of the controls. T(a) values at the onset of tail skin vasodilation and cold-induced thermogenesis of the exercise-trained rats were higher than those of the controls. The results suggest that, in rats, exercise training with a running wheel elevates ambient temperatures for heat loss and heat production, which may then contribute to maintaining the core temperature at a high level.

Adaptation, Physiological↗
PubMed2000

Influence of sex and age on serum nitrite/nitrate concentration in healthy subjects.

Measurement of serum nitrite/nitrate (NOx) concentrations has been considered useful to estimate nitric oxide production in humans. However little is known about the physiologic range and the factors affecting serum NOx levels. The aim of this study was, thus, to investigate the influence of sex and age on serum NOx levels in healthy subjects. We selected 263 healthy subjects (118 women and 145 men, 20-69 y) from 505 consecutive subjects who received annual medical checkups at our hospital. Serum NOx levels were determined using an analyzer employing the Griess method. The linear regression analysis showed that NOx increased significantly according to age in women (r=0.22, P<0.05), but did not in men (P=NS). Women of the younger age group (<40 y) showed significantly lower NOx levels than men of the same age group (P<0.05), whereas there was no significant difference between men and women of the older age (> or =40 y). Then, to investigate whether menopause affects serum NOx levels, middle aged women (46-55 y) were selected. Multiple logistic regression analysis showed that menopause was an independent factor for increased serum NOx levels in middle aged women (r=0.4, P<0.05). These results suggest that the serum NOx concentration is affected by age in healthy women, possibly depending on menopausal state.

Age Factors↗
PubMed2000

In vitro selection of aptamers that act with Zn2+.

An in vitro selection was carried out with Zn2+ to isolate novel RNA molecules, zinc-dependent aptamers, that bind to HIV-1 Tat protein. RNAs bound to Tat were collected by using a nitrocellulose filter from a library of random RNAs and regenerated to the next generation of the RNA library by subsequent reverse transcription, polymerase chain reaction, and transcription. Sequences of the selected RNAs were determined after 6 and 12 rounds of the selection. The control clones after normal selection procedure with Mg2+ had a consensus UUG that resembled essential sequences of TAR or Arg aptamers. On the other hand, many unique sequences were revealed from a library selected with Zn2+ and the RNA with most abundant sequence (clone 31) bound to Tat tightly only when Zn2+ existed. The secondary structure of clone 31 RNA was predicted by using a computational prediction with our thermodynamic parameters and enzymatic scission of the RNA. Several model RNAs were prepared and the binding property of these RNAs to Tat were investigated. As a result, all the model RNAs did not reproduce the binding property of clone 31. Therefore, the Tat aptamer that acts with Zn2+ should require a relatively longer region of the sequence which is able to offer tertiary cooperation of several motifs for the binding.

Base Sequence↗
PubMed2000

Effects of metal ions and catalytic loop sequences on the complex formation of a deoxyribozyme and its RNA substrate.

A deoxyribozyme is a catalytic DNA that catalyzes a site-specific RNA cleavage activity and requires various divalent cations. Earlier we have reported that by downsizing the catalytic loop of a deoxyribozyme from 15-mer to 11-mer it resulted in a short and novel Ca2+-dependent deoxyribozyme. In this paper, we investigate the complex formation of deoxyribozymes with their RNA substrates by using surface plasmon resonance (SPR) in order to determine quantitatively the effect of Ca2+ or Mg2+ on the recognition step between a deoxyribozyme and its RNA substrate. The results indicate that both the association and dissociation rate constants (k(a) and k(d)) for the deoxyribozyme-RNA complex depends on metal ions as well as the loop size of the deoxyribozyme. Metal ions with high RNA cleavage activity induced an increase in k(a) and a decrease in k(d). On the basis of the results, we propose that Ca2+ ions may play a role in the rearrangement of the 11-mer catalytic loop of the short Ca2+-dependent deoxyribozyme.

Calcium↗
PubMed2000

Constituents and their sweetness of food additive enzymatically modified licorice extract.

Enzymatically modified licorice extract (EMLE) is a natural sweetener, which is prepared with cyclodextrin glucanotransferase. It is used because of its unique properties such as higher solubility and better taste than those of licorice extract. In the present paper, the structures of six major constituents isolated from EMLE were determined, and their sweetness was studied. The isolated compounds were glycyrrhizin (1), 3-O-[beta-D-glucuronopyranosyl-(1-->2)-beta-D-glucuronopyranosyl]liquiritic acid (2), and their derivatives glucosylated at the C-4 position of the terminal glucuronopyranose with additional one (3 and 4, respectively) and two (5 and 6, respectively) glucose moieties. Compounds 1 and 2 are the major and minor sweet constituents in licorice extract, respectively. Compounds 3-6 are new compounds isolated for the first time. Compound 2 was sweeter than compound 1. Interestingly, compound 3, which is a monoglucosylated derivative of compound 1, was sweeter than compound 4. The sweetness of both compounds was lower than that of the parent compounds, while the lingering sweet aftertaste was markedly improved. Compounds 5 and 6, which have two additional glucose moieties, showed only slight sweetness.

Food Additives↗
PubMed2000

Effect of vitamin E on aspirin-induced gastric mucosal injury in rats.

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of alpha-tocopherol (vitamin E-deficient), 2 mg/100 g of alpha-tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of alpha-tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCI created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.

Animals↗
PubMed2000

Complexation of peptide with Cu2+ responsible to inducing and enhancing the formation of alpha-helix conformation.

Role of some metal ions on the conformations of peptides was examined by using a series of short alanine-based peptides with single Trp-His (W-H) interaction in different environments. Circular dichroism (CD), Trp (W) fluorescence emission, and Fourier transform infrared (FTIR) spectroscopy revealed that there is a conformational role of Cu2+ in inducing and enhancing the formation of alpha-helix conformation. The complexation of the peptide with Cu2+ is responsible to the conformational effect because the chelation is able to stabilize peptide with an alpha-helix conformation. The possible factors affecting the role of Cu2+ are discussed in the paper. The results in this paper are useful to understand the important structural role of Cu2+ in protein folding and the possible mechanism in some neurodegenerative diseases such as Alzheimer's disease.

Amino Acid Sequence↗
PubMed2000

Endosseous titanium implants as anchors for mesiodistal tooth movement in the beagle dog.

The purpose of this study was to determine the anchorage potential of titanium implants (Branemark; 3.75 x 7 mm) with the use of a sectional arch wire technique for orthodontic mesiodistal tooth movement, as assessed by the osseointegration of implants and tooth movement. Two implants were surgically placed in healed mandibular extraction sites of the second and third premolars on each side in 4 adult male beagle dogs. The implants were surgically uncovered 18 weeks later, and second-stage abutments with soldered edgewise tubes were attached. Segmented edgewise rectangular archwires (0.017 x 0. 025 inch) with a T-loop or an L-loop were placed between the implants and the fourth premolars on both sides as the anchorage unit. One segment in each dog served as a loaded side, and the archwire was calibrated to produce 200 g of lateral force on the fourth premolar. The contralateral segment served as an unloaded side and was not subjected to orthodontic force. Sectional wires were activated biweekly 24, 28, 28, and 32 weeks, respectively, depending on the magnitude and the appearance of mesial tipping movement of the fourth premolar. After mandibular impressions were taken to measure the distance between the first molar and the fourth premolar, the animals were euthanized and dissected mandibles were prepared. The specimens were then embedded in polyester resin and cut to take backscattered electron images. On the basis of these images, the percentage of peri-implant bone volume was calculated and defined as an index of osseointegration. The differences between the initial and final fourth premolar to first molar distances varied (7.40, 8.85, 10.50, and 3.30 mm) on the loaded side, whereas the unloaded side showed no movement. Not only was there no statistical difference in the percent of peri-implant bone volume between the loaded and unloaded sides, but there was also no statistical difference between the compression and tension sides in both loaded and unloaded implants, which suggests that the implants maintained rigid osseointegration. In conclusion, the present study demonstrated that endosseous titanium implants can function as anchors for long-term orthodontic mesiodistal movement.

Alveolar Process↗
PubMed2000

Odor distinctiveness between enantiomers of linalool: difference in perception and responses elicited by sensory test and forehead surface potential wave measurement.

The effects on humans of inhalation of optically active linalools were examined in terms of sensory tests and portable forehead surface electroencephalographic (IBVA-EEG) measurements in order to assess their odor distinctiveness by chiral isomers. (R)-(-)-Linalools with specific rotation of [alpha](D) = -15.1 degrees were isolated by repeated flash column chromatography from lavender oil, while (S)-(+)-linalools with [alpha](D) = +17.4 degrees and (RS)-(+/-)-linalools with [alpha](D) = 0 degrees and content of (R)-form 50.9% and (S)-form 49.1% were obtained from coriander oil and commercial linalool, respectively, by using the same method. With the use of an inhalator, each was administered to subjects both before and after 10 min of work. It was found that administration after work evoked different subjective impressions when compared with that before work depending on the configuration of the isomers and the type of work employed. For instance, inhalation of (R)-(-)-linalool after hearing environmental sounds not only produced a much more favorable impression in the sensory test but was also accompanied by a greater decrease in beta waves after work in comparison with that before work. This is in contrast to the case of mental work, which resulted in a tendency for agitation accompanied by an increase in beta waves. These findings led us to conclude that enantiomeric stereospecificity of linalool evoked different odor perception and responses not only with chiral dependence but also with task dependence. In addition, in comparing these sensory profiling features and IBVA-EEG tendencies between hearing environmental sound and mental work, a tendency was observed for (R)-(-)-linalool to coincide with (RS)-(+/-)-linalool but not with (S)-(+)-linalool.

Acyclic Monoterpenes↗
PubMed2000

New thermodynamic characterization and transition mechanism of DNA duplex formation.

A new transition mechanism of DNA duplex association was proposed and a segregated transition model (STM) was further derived. The experimental results in various molar ratios showed that the duplex association transition is imperfect and the thermodynamic properties and self-transition behavior of single strands exert a significant influence on DNA duplex formation.

Base Sequence↗
PubMed2000

Development of a novel functional biosensor with a short Ca(2+)-dependent deoxyribozyme.

We develop a novel functional biosensor on a deoxyribozyme. A 5'-end-immobilized short Ca(2+)-dependent deoxyribozyme (dCGCTGGCAGGCTACAACGAGTCTTC) binds to a target RNA substrate (rGAAGACA decrease UGCCAGCG; decrease denotes an RNA cleavage site), and acts as an enzyme in the presence of Ca2+. It cleaves the target RNA substrate at one site of rAp decrease U in the asymmetric internal loop.

Base Sequence↗
PubMed2000

Mass, momentum, and energy transfer by the propagation of acoustic solitary waves

This paper considers the mass, momentum, and energy transfer accompanied by the propagation of the acoustic solitary wave in a gas-filled tube. As was demonstrated previously [J. Acoust. Soc. Am. 99, 1971-1976 (1996); Phys. Rev. Lett. 83, 4053-4056 (1999)], the propagation of the solitary waves is made possible by connecting a periodic array of Helmholtz resonators axially with the tube. The solitary wave can convey the mass, momentum, and energy steadily with a constant speed that is subsonic but nearly equal to the linear sound speed. It is emphasized that the quantities transferred are of first order in magnitude. Formulating the basic equations in the conservation form, the total amount of the mass, momentum, and energy transferred is obtained by using the solitary-wave solutions. It has the upper bounds determined by the limiting solitary wave, which are proportional to the size of the resonator and the inverse of its natural frequency. In evaluating the energy transfer, a clear distinction should be made between the gas-dynamic energy and the acoustic energy. The former, which contains the first-order quantity whereas the latter begins with the quadratic ones, is to be used to determine the energy transfer in the form of heat (internal energy) associated with the mass transfer.

Journal Article↗
PubMed2000

Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase- and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N(17)-Cdc42, but not N(19)-RhoA, suppressed S1P- and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling.

3T3 Cells↗
PubMed2000

Role of the Y1 receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Y1 receptor-deficient, and Y5 receptor-deficient mice.

Neuropeptide Y (NPY) increases food intake through the action of hypothalamic NPY receptors. At least six subtypes of NPY, peptide YY (PYY), and pancreatic polypeptide (PP) receptors have been identified in mice. Although the involvement of Y1 and Y5 receptors in feeding regulation has been suggested, the relative importance of each of these NPY receptors and the participation of a novel feeding receptor are still unclear. To address this issue, we generated a Y1 receptor-deficient (Y1-/-) and a Y5 receptor-deficient (Y5-/-) mouse line in which we directly compared the orexigenic effects of NPY and its analogs after intracerebroventricular (icv) administration. The icv NPY-induced food intake was remarkably reduced in Y1-/- mice, but was not significantly altered by inactivation of the Y5 receptor. The Y1 receptor therefore plays a dominant role in NPY-induced feeding. Stimulation of feeding by moderately selective Y5 agonists [PYY-(3-36), human PP, and bovine PP] was reduced in Y5-/- mice, although food intake did not decrease to vehicle control levels. These results indicate that the Y5 receptor functions as one of the feeding receptors. In addition, the finding that Y5-preferring agonists still induce food intake in Y5-/- mice suggests a role for another NPY receptor(s), including the possibility of novel NPY receptors. Surprisingly, despite the limited efficacy of PYY-(3-36) and PPs at the Y1 receptor, food consumption induced by these agonists was significantly diminished in Y1-/- mice compared with that in wild-type controls. These observations suggest that the feeding stimulation induced by NPY and its analogs may be directly or indirectly modulated by the action of the Y1 receptor. We conclude that multiple NPY receptors, possibly including the novel feeding receptor, are involved in the feeding response evoked by NPY and its analogs. Among them, the Y1 receptor plays a key role in NPY-induced feeding in mice.

Animals↗
PubMed2000

Two new alkaloids from cigarette smoke condensate.

Chemical constituents of MeOH extracts of cigarette smoke were studied. Two new alkaloids, named cigatin A (1), 2-(Pyridine-3-yloxy)-benzene-1',4'-diol and B (2), 2-(4-Methyl-pyridin-3-yloxy)-benzene-1',4'-diol, were isolated from a mainstream condensate of cigarette together with seven known alkaloids. Their structures were determined on the basis of spectral data and chemical methods.

Alkaloids↗
PubMed1999

Vagotomy does not affect thermal responsiveness to intrabrain prostaglandin E2 and cholecystokinin octapeptide.

Subdiaphragmatic vagotomy has been repeatedly shown to attenuate the febrile response to peripherally injected pyrogens. In the present study, we investigated whether vagotomy-induced attenuation of febrile responsiveness reflects a decreased sensitivity of the brain to central fever mediators, prostaglandin E2 (PGE2) and cholecystokinin octapeptide (CCK-8). Male rats were subjected to subdiaphragmatic vagotomy (or sham surgery) on day 0 and had a cannula implanted into the lateral cerebral ventricle on day 24. On day 30-36, the thermal responsiveness of the rats to PGE2 or CCK-8 was tested. Each animal was injected in the ventricle with either PGE2 (0, 10, 100, or 500 ng) in pyrogen-free saline with 0.5% ethanol (5 microl) or CCK-8 (0 or 1.6 microg) in artificial cerebro-spinal fluid (5 microl). While the 0-dose of either PGE2 or CCK-8 (vehicle alone) induced no thermal response, all the higher doses of either agent caused a body temperature rise preceded by tail skin vasoconstriction. The vagotomized rats did not respond differently than their sham-operated counterparts to any dose of either drug. It is concluded that subdiaphragmatic vagotomy does not change the rat's thermal responsiveness to intrabrain PGE(2) and CCK-8.

Animals↗