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Biomedical subjects

T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 253 records · Page 14Linked to original sources
PubMed1988

Effect of intrahypothalamic hydroxybutyrate on sympathetic firing rate.

Following the microinjection of 3-hydroxybutyrate into either the paraventricular or ventomedial nucleus of the hypothalamus, there was a significant increase in firing rate of the sympathetic nerves to brown adipose tissue, with a peak increase in activity occurring three minutes following the injection. The response in both hypothalamic regions was dose-dependent. When injected into both regions at the same time, the increase in firing rate was additive. These studies suggest that ketone bodies in the central nervous system may activate the sympathetic nervous system.

3-Hydroxybutyric Acid↗
PubMed1988

The body weight loss of young rats caused by hepatic branch vagotomy is influenced by environmental temperature.

Changes in body weight after hepatic branch vagotomy or sham vagotomy were examined in rats of three different body weights (about 100, 200 and 280 g), and it was noted that the weight loss was evident only in 100 g rats. In a second experiment, 100 g animals were hepatic branch vagotomized or sham operated and housed at three different room temperatures (12-17, 17-22, 22-27 degrees C). Subsequently, the reduction in weight of the vagotomized animal was correlated with the lowest room temperature in the vagotomized animal, and food intake was also decreased in direct relation to the temperature. The results suggest that there might be a hepatic vagal mechanism modulating food intake in young animals, and such a mechanism may be modulated by the environmental temperature.

Afferent Pathways↗
PubMed1988

Structural features unique to each of the three antigenic sites on the hemagglutinin-neuraminidase protein of Newcastle disease virus.

Antigenic variants of D26 strain of Newcastle disease virus (NDV) were selected with monoclonal antibodies directed to the three nonoverlapping antigenic sites on the hemagglutinin-neuraminidase (HN) protein, and their HN genes were sequenced to identify the amino acids important for the integrity of each site. Seven variants for site I, which is immunodominant and conserved among NDV strains, had a change of glutamic acid at position 347, mostly to lysine, and in a single case, to glycine. In the second group of two variants for site IV, a change of asparagine to aspartic acid was found at position 481. This resulted in elimination of the oligosaccharide attached to this asparagine residue of the parental virus. Together with the finding that the site IV was destroyed by treatment with endoglycosidase F, it was suggested that the oligosaccharide is important for maintaining the structure of site IV. The oligosaccharide appeared to contribute to exposing a nearby determinant by conferring hydrophilicity on it. A variant for site II had also a nonconservative mutation resulting in the change of glutamic acid to valine at position 495. The site I recognized by antibodies which inhibit neuraminidase activity with a small substrate neuraminlactose was located closer to the predicted sialic acid-binding site than to the other sites recognized by antibodies lacking the enzyme-inhibiting capacity. The sequence of the parental virus HN gene revealed that the HNo precursor for the HN protein is an extra-long protein whose C terminus is elongated by 45 amino acids, compared with the usual HN protein sequenced in parallel.

Amino Acid Sequence↗
PubMed1988

Effect of fenfluramine on sympathetic firing rate.

The effects of acute and chronic treatment with fenfluramine have been explored in two experiments. Three and twenty-four hours following the injection of fenfluramine 20 mg/kg the firing rate of sympathetic efferent nerves to brown adipose tissue was significantly increased compared to sham injected controls. Body weight loss following acute treatment with fenfluramine was significantly greater at three and twenty-four hours than in the vehicle-treated controls. In the chronic experiment animals were treated once daily for 12 days with 20 mg/kg of fenfluramine. There were two control groups. One control group ate ad lib and a second control group was pair fed to maintain body weight comparable to that of the fenfluramine-treated animals. By the twelfth day food intake in the fenfluramine-treated animals had returned to control levels. Sympathetic firing rate after three days of treatment with fenfluramine was significantly higher in the treated animals than in ad lib fed controls. The ad lib fed controls were likewise significantly higher than the vehicle-treated, pair-gained controls. After 12 days of treatment fenfluramine treated animals had sympathetic firing rates which were still slightly but significantly higher than those of the vehicle-treated controls whereas the vehicle-treated, pair-gained animals had a small but significantly reduced firing rate. These data support the hypothesis that fenfluramine can increase peripheral sympathetic activity.

Animals↗
PubMed1988

The role of alpha 1-adrenoceptor-mediated collateral excitation in the regulation of the electrical activity of locus coeruleus neurons.

The physiological role of two types of autoreceptors, alpha 1- and alpha 2-adrenoceptors, located on the somadendritic membranes of locus coeruleus neurons, was studied in the developing and adult rat brain. Animals from birth to adulthood were anesthetized with urethan, and single-unit activity was recorded extracellularly in the locus coeruleus. The spontaneous firing of most locus coeruleus neurons was inhibited by iontophoretic application of noradrenaline at a high concentration, while noradrenaline at a low concentration frequently caused excitation of the neurons, predominantly in the developing brain. A similar excitation was also produced by iontophoretic application of the alpha 1-agonist phenylephrine. These excitations were antagonized by the alpha 1-antagonist, 2-beta [4-hydroxyphenylethylaminomethyl]-tetralone, while this antagonist had little effect on glutamate-induced excitation. The noradrenaline- and phenylephrine-induced excitation occurred more frequently in the neurons having little or no spontaneous activity. Electrical stimulation of the dorsal noradrenergic bundle arising in the locus coeruleus produced both inhibition and excitation. The excitatory responses were manifest primarily in early developmental stages, and occurred predominantly when the neurons had little or no spontaneous activity. When the neurons began firing at relatively high rates, the effects of dorsal noradrenergic bundle stimulation became principally inhibitory. Since the excitation evoked by dorsal noradrenergic bundle of stimulation was blocked by the alpha 1-antagonist, the excitation was thought to result from activation of alpha 1-adrenoceptors by noradrenaline released from the terminals of recurrent axon collaterals of locus coeruleus neurons themselves.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1988

Sympathetic activity following paraventricular injections of glucose and insulin.

The effect of microinjections of glucose and insulin into the paraventricular nucleus (PVN) on sympathetic firing rate has been examined in rats. Following the injection of insulin 144 pmoles, there was a 30% reduction in sympathetic firing rate with a minimum reached 2 minutes following the injection, and recovery to baseline within 4 minutes. Lower doses of insulin were without effect. Following the injection of glucose 138 nmoles, there was a brief 20% increase in sympathetic firing rate which peaked at 1 minute and had returned to control levels by the second minute. This effect of glucose, like that of insulin, was dose-related. When compared with injections of insulin and glucose into the ventromedial hypothalamus, injection of either substance into the PVN showed a smaller and more attenuated response, raising the possibility that the effect of these nutrients injected into the PVN may be through the small quantities which could reach the ventromedial nucleus. These studies are consistent with the hypothesis that the paraventricular nucleus is not the principal modulator of the sympathetic firing rate.

Animals↗
PubMed1988

Sympathetic activity following paraventricular or ventromedial hypothalamic lesions in rats.

The present experiment was designed to measure the sympathetic firing rate of nerve filaments to interscapular brown adipose tissue in rats with acute and chronic lesions in the ventromedial hypothalamus or paraventricular nucleus. Female rats received injections of kainic acid into either the paraventricular nucleus or the ventromedial hypothalamus. The sympathetic activity was measured by recording the firing rate of nerve filaments to interscapular brown adipose tissue after mounting the filaments on silver wire electrodes connected to an amplifier and rate meter. In acute experiments performed 30 minutes after the lesion, the basal firing rate was reduced in both groups and was significantly lower in the VMH-lesioned rats than in those with PVN lesions. In the chronic experiment kainic acid was injected into the VMH or PVN and the sympathetic firing rate was measured 7 to 9 days later. Both lesioned groups gained more weight than controls, but the VMH-lesioned rats gained more weight than the PVN-lesioned rats. The basal firing rate of sympathetic nerve filaments in the VMH-lesioned rats was lower than in the other groups. There was no significant difference in the sympathetic activity between PVN-lesioned and control rats. These experiments support the hypothesis that lesions of the ventromedial hypothalamus reduce the sympathetic activity but that lesions in the paraventricular nucleus do not.

Adipose Tissue↗
PubMed1988

Regional differences in inhibition and recovery of protein synthesis after transient hindbrain ischaemia of gerbils.

Regional protein synthesis was estimated autoradiographically in a model of transient hindbrain ischaemia of gerbils. In studies of 5 min ischaemia followed by 5 min recirculation, incorporation of [14C]valine into the TCA-insoluble protein fraction was not affected. In studies of 15 min ischaemia followed by 5 min recirculation, incorporation of the tracer into the protein fraction was severely depressed in the ischaemic lesion of the brain stem and cerebellum. However, the granular layer of the cerebellar cortex had partially preserved protein synthesis. When recirculation time was extended to 2 h after 30 min ischaemia, protein synthesis of the cerebellar cortex almost recovered to the full level of the control. However, in the pontine grey matter, inferior colliculus and vestibular nucleus, a significant reduction in protein synthesis persisted. These results indicate that protein synthesis in the pontine grey matter, inferior colliculus and vestibular nucleus are selectively inhibited by ischaemia. Further its recovery after recirculation is slow. The cerebellar cortex is less vulnerable to ischaemia, and recovery is relatively fast. The regional heterogeneity of protein synthesis is neither due to the degree of ischaemia in this model nor the extent of postischaemic hypoperfusion. Factors that influence protein synthesis in this ischaemic model are discussed.

Animals↗
PubMed1988

Simple assay of beta-lactamase with agar medium containing a chromogenic cephalosporin, pyridinium-2-azo-p-dimethylaniline chromophore (PADAC).

A new beta-lactamase assay method with agar plates containing pyridinium-2-azo-p-dimethylaniline chromophore (PADAC) (50 microM), a beta-lactamase-labile, chromogenic cephalosporin, was examined. On the PADAC plates inoculated with beta-lactamase-producing gram-negative bacteria (10(4) CFU per spot) and incubated at 37 degrees C, a yellow zone showing hydrolysis of PADAC by beta-lactamase was formed around the colony. The zone diameter increased with incubation time. Examination with Enterobacter cloacae GN7471 revealed that beta-lactamase activity was present in the agar around the colony, decreasing exponentially with increasing distance from the colonial margin; this suggests that the PADAC hydrolysis zone is formed by an extracellular enzyme. At 18 h, significant correlations were obtained between the zone diameters of the 10 species (clinical isolates) examined and their periplasmic beta-lactamase activities determined spectrophotometrically. The addition of clavulanic acid (0.5 to 10 micrograms/ml) inhibited zone formation on the PADAC plates inoculated with type IIIa, Va, Vb, PSE-1, and Ic beta-lactamase producers. When the clinical isolates were tested on plates with clavulanic acid (2 micrograms/ml), inhibition was observed in 41 to 58% of the Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa isolates and in all isolates of Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus vulgaris. Thus, the use of the inhibitor made it possible to detect penicillinase or type Ic cephalosporinase producers. These results proved that the PADAC plate might be a useful tool permitting easy, semiquantitative determination of beta-lactamase activity.

Agar↗
PubMed1988

Distribution of cefpirome (HR 810) to exudate in the croton oil-induced rat granuloma pouch and its therapeutic effects on experimental infections in the pouch.

Therapeutic effects of intravenously administered cefpirome on experimental bacterial infections in croton oil-induced rat granuloma pouches were compared with those of ceftazidime, moxalactam, cefoperazone, and cefotaxime. Its pharmacokinetic profile in pouch exudate was also examined. Cefpirome showed bactericidal effects and long-lasting bacterial growth-inhibitory effects in granuloma pouches infected in Escherichia coli Ec-7, and its effects were almost equal to those of the other antibiotics. Against Pseudomonas aeruginosa TM-11 infection, cefpirome was more active than moxalactam, cefoperazone, and cefotaxime and comparable to ceftazidime. Cefpirome had the strongest activity against Staphylococcus aureus Smith infection among the five antibiotics, showing bactericidal effects and long-lasting bacterial growth-inhibitory effects. The level of cefpirome in pouch exudate peaked at 1 h after administration, with a value of 16.4 micrograms/ml, and declined in a pattern similar to that of ceftazidime. When compared in peak level, the exudate level of cefpirome was 1.8 to 2.6 times higher than the values of moxalactam, cefoperazone, and cefotaxime. The in vitro exudate protein binding of cefpirome was 8.8%, which was the lowest among the antibiotics used.

Animals↗
PubMed1988

Positive reaction in mouse ligated intestinal loop assay with nonenterotoxigenic and nonhemolytic strains of Staphylococcus aureus.

Nonenterotoxigenic and nonhemolytic strains of Staphylococcus aureus exhibited a positive reaction in the mouse intestinal loop assay except for a strain negative for the egg yolk reaction. Edema and swelling in all positive loops, increased bacterial cell numbers within intestinal loops, and extremely close adhesion to or inclusion of numerous bacterial cells in HeLa cells after inoculation of the strains were observed. These results suggest a possible invasive ability of the strains.

Animals↗
PubMed1988

Identification of amino acids relevant to three antigenic determinants on the fusion protein of Newcastle disease virus that are involved in fusion inhibition and neutralization.

Nucleotide sequence analysis of F protein antigenic variants of Newcastle disease virus mapped three distinct antigenic determinants to positions 343, 72, and 161 on the protein. The high fusion-inhibiting and neutralizing capacities of all of the monoclonal antibodies used for selection suggested close functional and structural relationships of the three positions with the fusion-inducing N-terminal region of the F1 subunit. The former two positions were located at the cysteine cluster domain near the C terminus of the F1 subunit and at the major hydrophilic domain in the F2 subunit, respectively, and both domains appeared to represent the major antigenic determinants of paramyxovirus F protein.

Amino Acid Sequence↗
PubMed1988

Effect of starvation and food intake on sympathetic activity.

These studies have examined the effect of fasting and nutrient loads on sympathetic firing rate in three groups of rats that develop widely divergent degrees of obesity when eating a high-fat diet. Starvation of Sprague-Dawley rats for 24 or 48 h was associated with a decrease in basal sympathetic activity of nearly 25% in the first 24 h and of slightly greater than 30% in 48 h. This decline in sympathetic activity paralleled the loss of body weight and reduction in adipose tissue mass. After starvation for 48 h, Osborne-Mendel rats, which readily develop obesity when eating a high-fat diet, showed a greater decrease in basal sympathetic activity than did the diet-resistant S 5B/P1 rats. A single liquid 36-kcal intragastric meal was associated with an acute 30% increase in sympathetic firing rate in the overnight-fasted Sprague-Dawley rats. The values 3 h after the meal had returned halfway to normal, and by 6 h they were more than 85% of the way to normal. An intravenous injection of glucose produced a greater rise in sympathetic activity in diet-resistant S 5B/P1 rats than in the diet-sensitive Osborne-Mendel rats. These data are consistent with the hypotheses that sympathetic activity is positively related to nutrient status, that it varies between strains of rats, and that it can be acutely increased by an intragastric meal or by intravenous glucose.

Adipose Tissue↗
PubMed1988

Lateral hypothalamus and sympathetic firing rate.

Measurements of sympathetic firing rate have been made after the acute microinjection of glucose or insulin into the lateral hypothalamic area as well as after ablation of this area with locally injected gold thioglucose. Injection of glucose into the lateral hypothalamus (LH) produced a small but significant and dose-dependent reduction in the firing rate of efferent sympathetic nerves to interscapular brown adipose tissue. Injection of insulin into the same region produced a very short-lived increase in efferent sympathetic firing rate. Bilateral lesions in the lateral hypothalamus produced by microinjection and gold thioglucose lowered body weight more than sham injections into the LH of control animals. There was an increase in basal sympathetic firing rate at 3, 9, and 24 h after LH lesions. There was also an increase in firing rate at 1 and 3 days, but by 7 days firing rate had returned to control levels. The data support the hypothesis that LH lesions enhance sympathetic activity but show only very limited modulation by glucose or insulin.

Adipose Tissue, Brown↗
PubMed1988

Diurnal changes in sympathetic activity. Relation to food intake and to insulin injected into the ventromedial or suprachiasmatic nucleus.

The present study was designed to test whether there are diurnal changes in the firing rate of sympathetic nerves to brown adipose tissue and whether these diurnal rhythms influenced the response to insulin injected into the suprachiasmatic nucleus or ventromedial hypothalamic nucleus (VMH). Food intake was highest at the beginning of the dark period (1800-2200 hours) and lowest during the daylight hours (0600-1000 and 1200-1600 hours). The basal sympathetic firing rate was highest at noon (1000-1200 hours) when food intake was lowest. At midnight, when food intake was highest, sympathetic firing rate was lowest. Injection of insulin (77, 144, and 288 pmol) into the VMH produced a dose-dependent depression of sympathetic firing rate at each of the four measurement periods (0400-0600 hours, 1000-1200 hours, 1600-1800 hours, and 2200-2400 hours), but the magnitude of the effect was greater at noon than at night. In contrast, insulin injections into the suprachiasmatic nucleus decreased the sympathetic firing rate at noon but produced a significant increase in the sympathetic firing rate at night. These data show that a diurnal rhythm exists for the sympathetic firing rate. The decrease in firing rate in response to insulin when injected into the VMH is in the same direction but varies in magnitude throughout the day, whereas the responsiveness of the suprachiasmatic nucleus to injections of insulin shows a reversal of response in relation to day/night cycles. The highly significant inverse relationship between basal sympathetic firing rate and food intake suggests that sympathetic activity may be part of an important control system for energy balance.

Action Potentials↗
PubMed1988

[Pharmacological comparison of the CNS effects of propentofylline and caffeine].

The CNS effects of propentofylline and caffeine, methylxanthine derivatives, were compared. In mice, caffeine antagonized diazepam-induced muscle relaxation and the inhibitory effect of diazepam against pentylenetetrazole-induced convulsions, but propentofylline did not. In spinal cats, the dorsal root reflex potentials were inhibited by caffeine but not affected by propentofylline, and the monosynaptic reflex potentials were increased by propentofylline but not influenced by caffeine. The results indicate that propentofylline differs from caffeine in that it neither antagonizes diazepam nor affects the GABA system.

Animals↗