Search PubMed⌕ Search

Biomedical subjects

N Sugimoto

Publications and source records attributed to N Sugimoto.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effects of non-steroidal anti-inflammatory drugs on prostaglandin E2 production by cyclooxygenase-2 from endogenous and exogenous arachidonic acid in rat peritoneal macrophages stimulated with lipopolysaccharide.

Lipopolysaccharide (LPS) stimulated prostaglandin E2 (PGE2) formation and induction of cyclooxygenase-2 (COX-2) expression without changing the levels of COX-1 protein in rat peritoneal macrophages. Non-steroidal anti-inflammatory drugs (NSAIDs) (nimesulide, indomethacin and ibuprofen) strongly inhibited LPS-stimulated PGE2 production without any effect on COX-2 protein expression, suggesting that NSAIDs are active in inhibiting the ability of COX-2 to convert arachidonic acid (AA) endogenously released in response to LPS stimulation. Exogenous AA can be converted to PGE2 by both COX isoforms even in LPS-stimulated macrophages. NSAIDs inhibited PGE2 production from exogenous AA mediated by both COX-1 and COX-2. However, the two isoforms interacted differentially with different NSAIDs. Furthermore, NSAIDs were distinctly more active in inhibiting PGE2 production from endogenous AA than that from exogenous AA. These data suggest that PGE2 production through COX-2 from exogenous AA may not be subject to the same regulatory processes as that from endogenous AA and the two metabolic processes may be differentially sensitive to different NSAIDs.

Animals↗
PubMed1996

Endotoxin shock: thermoregulatory mechanisms.

To clarify mechanisms of hypothermia in lipopolysaccharide (LPS) shock, four experiments were conducted in 72 chronically instrumented Wistar rats. They were intended to accomplish the following: experiment 1, determine the dose of intravenous Escherichia coli LPS that induces a body temperature (Tb) fall at a minimal mortality [the dose chosen (0.5 mg/kg) was then used in experiments 2-4]; experiment 2, identify the time course of the arterial blood pressure (BP) fall (shock) during the response to LPS; experiment 3, measure threshold Tb values for skin vasodilation and activation of metabolic heat production (M) during the LPS shock; and experiment 4, ascertain behavioral thermoregulation in LPS shock. For experiments 1-3, rats were kept in restrainers; ambient temperature (Ta) was 26 degrees C. In experiment 4, rats freely moved in a thermogradient (18-33 degrees C). Variables monitored were colonic (Tc) and tail skin (Tsk) temperatures (experiment 1); BP (experiment 2); hypothalamic temperature (Thy), M (from oxygen consumption), and Tsk (experiment 3); and preferred Ta (Tpr) and abdominal temperature (experiment 4). In experiment 1, LPS induced no Tc changes at 0 mg/kg, a biphasic fever (no mortality) at 0.05 mg/kg, a biphasic hypothermia (42% mortality) at 0.5 mg/kg, and a rapid fall of Tc (100% mortality) at 5 mg/kg. LPS-induced (0.5 mg/kg) hypotension (experiment 2) occurred simultaneously with the first hypothermic phase; both Tc and BP reached their nadirs (-0.8 +/- 0.1 degrees C and -34 +/- 12 mmHg) at approximately 1.5 h post-LPS. The major autonomic mechanism of the shock hypothermia was a shift in the threshold Thy for M from 37.9 +/- 0.3 to 36.0 +/- 0.3 degrees C (experiment 3; P < 0.05). In experiment 4, rats selected Tpr below 25 degrees C (vs. 28-30 degrees C in control; P < 0.05) throughout the duration of the shock; their Tb dropped to 36.2 +/- 0.3 degrees C (P < 0.05). In sum, the LPS shock-associated hypothermia involves a decrease in the threshold Tb for M, the resultant widening of the interthreshold zone, and cold-seeking behavior.

Animals↗
PubMed1996

Cellular antioxidant defense by a ubiquinol-regenerating system coupled with cytosolic NADPH-dependent ubiquinone reductase: protective effect against carbon tetrachloride-induced hepatotoxicity in the rat.

We found that NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) in rat liver cytosol reduces ubiquinone (UQ) to ubiquinol (UQH2) in lipid membranes and consequently inhibits lipid peroxidation [Takahashi T., et al., Biochem. J., 309, 883-890 (1995)]. Here we examined whether or not this UQH2-regenerating system functions as a cellular antioxidant defense in animals. Rats were given UQ-10 for 2 weeks, and were then exposed to carbon tetrachloride (CCl4). The UQ-10 supplement increased only in the NADPH-UQ reductase and the UQH2-10 pool of rat liver without any appreciable change in the levels of other antioxidant factors. On the other hand, CCl4 markedly increased plasma aspartate aminotransferase and alanine aminotransferase, liver weight and thiobarbituric acid reacting substances formation, which are indicators of CCl4-hepatitis, and it decreased the liver levels of L-ascorbic acid, reduced form of glutathione (GSH), alpha-tocopherol, NADPH-UQ reductase and glutathione S-transferase. However, all the above indicators of CCl4-induced hepatitis were significantly improved in rats given UQ-10. Furthermore, alpha-tocopherol, but neither L-ascorbic acid nor GSH, was significantly saved. UQ-10 supplement also was recovered glutathione S-transferase and NADPH-UQ reductase activities slightly. These results indicated that UQ-10 given to rats increased the cellular UQH2-10 pool and cytosolic NADPH-UQ reductase activity in their livers, resulting in the inhibition of lipid peroxidation in the biomembranes, and consequently protected the rats from the CCl4-hepatotoxicity.

Animals↗
PubMed1996

Day-night variations of behavioral and autonomic thermoregulatory responses to lipopolysaccharide in rats.

This study investigated the day-night differences in behavioral and autonomic thermoregulatory responses to bacterial lipopolysaccharide (LPS) in rats. Male rats were housed individually in cages with a 12: 12 h light dark cycle at an ambient temperature of 24 degrees C. The rats were placed in a box with a temperature gradient and intraperitoneally injected with LPS (10 micrograms/kg). The preferred ambient temperature (Tpr) was estimated by the location of the rats in the box, and intraperitoneal temperature (Tb) was measured by a biotelemetry system. Measurements were taken during the light and dark phases of the day. LPS produced fever in both phases. The magnitude of rise in Tb did not differ between the two periods. In the dark phase, Tpr significantly increased during the development of fever and decreased during the defervescence, while it did not change throughout the febrile course during the light phase. In a separate experiment, rats were loosely restrained and placed in a direct calorimeter. Their colonic temperature (Tcol), evaporative and nonevaporative heat loss and heat production were measured before and after intraperitoneal injections of LPS (10 micrograms/kg). Measurements were taken during the light and dark phases of the day. LPS induced fever in both phases. The magnitude of change in T col, heat loss, and heat production due to LPS did not differ between the two periods. These results suggest that the fertile response of rats to intraperitoneal LPS is not affected by the time of day. However, it seems that during LPS-induced fever, thermoregulatory behavior is not fully activated during the light phase of the day.

Animals↗
PubMed1996

[Changes in the working status of pulmonary tuberculosis patients after the admission].

We reported changes in the working status of pulmonary tuberculosis patients after the admission to our hospital. The age of patients ranged from 20 to 69 years old, and they were admitted to the 18th ward of our hospital from April 1991 to March 1993. We sent out the questionnaire to 198 patients, and the reply was sent back from 116 patients (Male 74, Female 42). Out of the 116 patients, we excluded the unemployed, the government employees, and self-employed workers. The remaining 76 patients were examined about their working status after admission, and the results were as follows: 2 patients lost their work, 11 patients retired from the work, 2 patients faced the drop of their position, and 3 patients had their salary reduced.

Adult↗
PubMed1995

Thermodynamic parameters to predict stability of RNA/DNA hybrid duplexes.

The thermodynamic parameters (delta H degree, delta S degree, and delta G degree 37) for 16 nearest-neighbor sets and one initiation factor are presented here in order to predict stability of RNA/DNA hybrid duplexes. To determine the nearest-neighbor parameters, thermodynamics for 68 different hybrid sequences (136 single-stranded oligonucleotides) with 5-13 nucleotide length including several duplexes with identical nearest-neighbors were measured by UV melting procedure. These sequences were selected to have many different combinations of nearest-neighbor pairs, and so that the number of the 16 nearest-neighbor sequences in the oligomers were as equal as possible. The structures of the hybrids were also investigated by measuring circular dichroism spectra. Comparing delta G degree 37 values of the hybrids with DNA/DNA and RNA/RNA parameters reported previously (Breslauer, K.J., Frank, R., Blöcker, H., & Marky, L.A. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3746-3750; Freier, S.M., Kierzek, R., Jaeger, J.A., Sugimoto, N., Caruthers, M.H., Neilson, T., & Turner, D.H. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 9373-9377), RNA/RNA double helix is the most stable of the three kinds of helixes with the same nearest-neighbor sequences. Which is more stable between DNA/DNA and RNA/DNA hybrid duplexes depends on its sequence. Calculated thermodynamic values of hybrid formation with the present parameters reproduce the experimental values within reasonable errors.

Base Sequence↗
PubMed1995

Female reproductive properties and prenatal development of a senescence-accelerated mouse strain.

Female reproductive properties, early embryonic development, and serum estradiol and progesterone levels of the senescence-accelerated mouse (SAM)-prone (SAM-P) strain were compared with those of a SAM-resistant (SAM-R) strain. The reproductive life span of SAM-P (from 11.4 to 25.0 weeks old) was shorter than that of SAM-R (11.1 to 41.6 weeks old), and the total number of SAM-P pups was 41.7% less than from SAM-R. The reproductive senescence of SAM-P is more accelerated than that of SAM-R. At 15 weeks old, the maximum litter size of SAM-P was noted and was 33.7% smaller than that of SAM-R. Although no differences in the numbers of ovulated and fertilized ova were observed between two strains, the number of implants in SAM-P was 21.6% less than in SAM-R. Cell cleavage was delayed in embryos of SAM-P (8% morula, at day 2 of pregnancy) compared to SAM-R (48%). At day 3 of pregnancy, 9% and 33% of the embryos were blastocysts in SAM-P and SAM-R, respectively. At day 1 of pregnancy, serum estradiol level in SAM-P was 18.2% higher than in SAM-R, whereas the serum progesterone level in SAM-P was 46.2% lower than in SAM-R. The unbalance of estradiol and progesterone levels in SAM-P was considered to be the cause of the delay in early embryonic development, and then the decrease of implantation and a smaller litter size.

Aging↗
PubMed1995

Influence of alpha-deoxyadenosine on the stability and structure of DNA. Thermodynamic and molecular mechanics studies.

The alpha anomer of deoxyadenosine (alpha) and an abasic site (tetrahydrofuran, F), which are DNA lesions produced by free radicals, were site-specifically incorporated in 9-mer duplexes d(TGAGXGTAC).d-(GTACNCTCA), where X = alpha or F and N = A, G, C, or T. Their influence on thermodynamic stability and structure of DNA was assessed by UV-melting measurements and molecular mechanics calculations. UV-melting studies revealed that a duplex containing an alpha T pair was as stable as the parental duplex containing an AT pair at the same site. Furthermore, the stability of duplexes containing alpha varied depending on the base opposite this lesion, with the Tm decreasing in the following order: alpha T > alpha C approximately alpha A > alpha G. On the contrary, an abasic site introduced in the same site showed a significantly greater destabilizing effect than alpha, but variation of Tm with the bases opposite F was less evident. To delineate the molecular mechanism of thermodynamic effects of an alpha lesion, molecular mechanics calculations were performed for the same duplexes as used for UV-melting measurements. The results suggest that the structural perturbation introduced into DNA by an alpha N pair is alpha G > alpha A > alpha C > alpha T, showing a parallel correlation with the destabilizing effects of alpha N pairs. On the basis of these results, it is discussed how the perturbations introduced by these DNA lesions may influence the selection of nucleotides opposite the lesions by DNA polymerases and the interaction with DNA repair enzymes such as Escherichia coli endonuclease IV and exonuclease III.

Base Sequence↗
PubMed1995

Shifts of thermoeffector thresholds in heat-acclimated rats.

1. Heat-acclimated (HA) rats, kept under a 12:12 h light-dark regime, were subjected to an ambient temperature (Ta) of 33 degrees C for 5 h in the last half of the dark phase for 3 weeks. Control rats were kept under a 12:12 h light-dark regime at a constant Ta of 24 degrees C. 2. After the acclimation period, the rats were then placed in a metabolic chamber at a Ta of 26.5 degrees C, and body core temperature was gradually increased and decreased using an intravenous thermode. Thermoeffector thresholds were determined by the hypothalamic temperature (T(hy)) at the onset of warm-induced tail skin vasodilatation and cold-induced thermogenesis measured by oxygen consumption. 3. Each rat was subjected to the experiment twice, once in the first half and once in the last half of the dark phase, on different days in random order. 4. In HA rats, T(hy) at the onset of both skin vasodilatation and thermogenesis were significantly lower in the last half of the dark phase compared with the first half. In control rats, however, there were no such differences between the two halves. 5. The results suggest that in rats acclimated to daily heat exposure, thermoeffector thresholds shift to lower temperatures only during the period of day when the rats had previously been exposed to heat.

Adaptation, Physiological↗
PubMed1995

On the mechanism of preferential incorporation of dAMP at abasic sites in translesional DNA synthesis. Role of proofreading activity of DNA polymerase and thermodynamic characterization of model template-primers containing an abasic site.

DNA polymerase preferentially incorporate dAMP opposite abasic sites (A-rule). The mechanism of the A-rule can be studied by analyzing three dissected stages of the reaction including (i) initial nucleotide insertion, (ii) proofreading excision of the inserted nucleotide and (iii) extension of the nascent primer terminus. To assess the role of the stage (ii) in the A-rule, kinetic parameters of the proofreading excision of primer terminus nucleotides opposite abasic sites were determined using E.coli DNA polymerase I Klenow fragment. The relative efficiency of the excision (Vmax/Km) revealed that removal of A was the least favored of the four nucleotides, but the differences in the efficiencies between excision of A and the other nucleotides was less than 2-fold. In addition, in an attempt to reconcile kinetic data associated with the stage (i) or (ii), the differences in free energy changes (delta delta G degrees) for the formation of model template-primer termini containing XN pairs (X = abasic site, N = A, G, C or T) were determined by temperature dependent UV-melting measurements. The order of delta delta G degrees was XG > XA = XC > or = XT, with delta delta G degrees being 0.5 kcal/mol for the most stable XG and the least stable XT. Based on these data, the role of the stage (ii) and energetic aspects of the A-rule are discussed.

Base Sequence↗
PubMed1995

The enterotoxin of Clostridium perfringens type A binds to the presynaptic nerve endings in neuromuscular junctions of mouse phrenic nerve-diaphragm.

The enterotoxin of Clostridium perfringens type A, a channel-pore forming protein toxin, inhibited neuromuscular transmission in isolated mouse phrenic nerve-diaphragm preparation at low concentrations of calcium. We investigated immunohistochemically the localization of the binding sites of the enterotoxin in the preparation under the conditions in which the enterotoxin reduced maximally the amplitudes of the twitch tension elicited by electrical stimulations to the phrenic nerve. Under the conditions, double immunohistochemical staining of the preparation with (1) rabbit anti-enterotoxin IgG-rhodamine-labeled goat anti-rabbit IgG and (2) mouse anti-synaptophysin (one of the synaptic vesicle-specific membrane proteins)-fluorescein isothiocyanate (FITC)-labeled goat anti-mouse IgG showed that the enterotoxin binds specifically to most of the sites which were stained with anti-synaptophysin exactly in the same configurations having the shapes of the nerve endings in the endplates. The thin section electron micrographs of the enterotoxin-intoxicated preparation showed no alterations in the ultrastructure of the neuromuscular junction and the nerve endings filled with numerous synaptic vesicles. The present results, together with our previous electrophysiological findings, indicate that the enterotoxin binds specifically to the presynaptic nerve endings and inhibits neurotransmitter release at the neuromuscular junction.

Animals↗
PubMed1995

Coronary vasoconstriction is the most probable cause of death of rats intoxicated with botulinolysin, a hemolysin produced by Clostridium botulinum.

The pathophysiology of lethal intoxication by botulinolysin (Blyn) was studied using anesthetized rats and isolated rat organs. Intravenous injection of 10,000 and 1000 hemolytic units (HU) of Blyn killed rats rapidly while 100 HU of the toxin did not. Congestion and edema of lungs were observed at autopsies of the rats killed by intoxication. Hemoglobinemia was obvious in rats injected with 1000 HU of Blyn but not in rats with 10,000 HU. Electrocardiograms of the intoxicated rats showed depression of T waves but not changes characteristic of hyperpotassemia. All the rats injected with the above doses of Blyn showed a rapid fall in arterial blood pressure (BP) immediately after the toxin injection, and BP soon recovered in rats injected with 100 HU, partially and transiently in rats with 1000 HU, and not in rats with 10,000 HU of Blyn. Perfusion of Blyn (1 HU/ml) to isolated rat hearts caused a rapid and marked increase in perfusion pressure and cessation of spontaneous heart beat. Acetylsalicylic acid (10(-3) M) and quinacrine dihydrochloride (10(-5) M) did not essentially influence the effects of Blyn on the isolated hearts, but verapamil (10(-6) M) inhibited at least the initial increase in perfusion pressure elicited by Blyn. Spontaneous contractions of the isolated atria were little influenced by Blyn (60 HU/ml). Perfusion pressures of isolated kidneys, lungs and livers were also increased by Blyn (1 HU/ml). The results indicate that Blyn caused vasoconstriction but had little direct effect on myocardium. Based on the above findings, we conclude that coronary vasoconstriction elicited by direct action of Blyn causes acute cardiac dysfunction leading to systemic hypotension and death of the intoxicated animals.

Animals↗
PubMed1995

Effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation in calvaria of neonatal rats.

The effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation were investigated using a purified toxin preparation. Single injection of 4.3 ng of the toxin into the subcutaneous tissue overlying the calvariae of neonatal rats necrotized periosteum of parietal bone and degenerated osteoblasts within two days. Nine days after the injection, the lesion of the bone tissue became severe; the bone matrix became thin and fragmented. These observations indicate that dermonecrotizing toxin without other factors produced by the organisms impairs bone formation.

Animals↗
PubMed1995

Effect of digital nerve blockade on heat-induced vasoconstriction in the human finger.

The present study was performed to investigate the mechanism of heat-induced vasoconstriction (HIVC) in human fingers. The left fingers of five male subjects were immersed in water controlled at an initial temperature of 35.0 degrees C. The blood flows (BF) of the left index and fourth fingers were measured continuously with laser-Doppler flowmeter probes, and the temperatures of the middle finger and water bath were also monitored continuously using thermistor probes. Arterial blood pressure and heart rate were measured every minute before and during local finger warming. A local anesthetic (0.5% bupivacaine hydrochloride) or saline at a volume of 5.0-8.0 ml was aseptically injected into the base of the fourth or index finger, respectively. After finger BFs had been stabilized for > or = 10 min, the fingers were warmed by raising the water bath temperature from 35.0 to 41.5 degrees C in 14 min. The BF of the index finger fell significantly for 6 min after local warming was commenced (at water bath temperatures between 35.5 and 37.5 degrees C) without associated changes in mean arterial blood pressure, indicating the occurrence of HIVC. Then BF increased toward prewarming levels. The local anesthetic injection, however, completely abolished HIVC in the fourth finger. These results suggest that, in humans, innervation to finger vessels is indispensable for producing HIVC and hence that a local mechanism, such as myogenic vascular response to high temperature, may not be involved in the induction of HIVC.

Blood Pressure↗
PubMed1995

Thermoregulatory responses of rats acclimated to heat given daily at a fixed time.

Body core temperature of rats acclimated to heat given daily at a fixed time falls during the previous heat exposure time. In the present study, thermoregulatory responses of heat-acclimated rats were examined during the specific period. Heat-acclimated rats were subjected to an ambient temperature of 32 degrees C for approximately 5 h in the first half or last half of the dark phase for 14 days while control rats were kept at 24 degrees C. Then the rats were placed in a direct calorimeter and were warmed for 30 min with an intraperitoneal electric heater. Measurements were made twice in the first and last halves of the dark phase. Body warming significantly increased body core temperature in all rats. In the heat-acclimated rats, heat production (M) was significantly depressed during the previous heat exposure time but not during the other period. Body warming had little effect on M in the control rats during either period. The results suggest that rats acclimated to heat given at a fixed time daily respond to an acute heat load with a pronounced reduction of M. However, such a response was observed only during the period when the rats had been previously exposed to heat.

Acclimatization↗
PubMed1995

Bordetella bronchiseptica dermonecrotizing toxin stimulates assembly of actin stress fibers and focal adhesions by modifying the small GTP-binding protein rho.

We studied the biochemical mechanism of morphological changes in cells treated with Bordetella dermonecrotizing toxin (DNT). DNT caused the morphological changes of serum-starved MC3T3-E1 cells from flat shapes to reflactile ones. These changes were accompanied by the assembly of actin stress fibers and focal adhesions, which is known to be regulated by the small GTP-binding protein rho. Clostridium botulinum C3 exoenzyme, which ADP-ribosylates and inactivates rho protein, 'rounded' the cells within 2 hours after addition to the extracellular fluid and their rounded shapes were maintained for at least 10 hours. However, when the cells were co-treated with C3 exoenzyme and DNT, they were rounded at 2 hours but recovered an apparently intact morphology after 3-8 hours of incubation. rho proteins in lysates from DNT-treated cells and untreated cells were radiolabeled by [32P]ADP-ribosylation with C3 exoenzyme and analyzed by SDS-polyacrylamide gel electrophoresis. Whereas the lysate from untreated cells showed a single band of [32P]ADP-ribosylated rho protein, the lysate from DNT-treated cells showed an additional two bands as well as the band identical to that of the lysate from untreated cells. Recombinant rhoA protein treated with DNT in vitro also showed a mobility shift in SDS-polyacrylamide gel electrophoresis. These results indicate that DNT causes the assembly of actin stress fibers and focal adhesions by directly modifying rho protein.

ADP Ribose Transferases↗