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J Noguchi

Publications and source records attributed to J Noguchi.

At least 55 records · Page 3Linked to original sources
PubMed1998

Synthesis and preliminary evaluation of [11C]NE-100 labeled in two different positions as a PET sigma receptor ligand.

N,N-Dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine (NE-100) was labeled with 11C in two different positions by the alkylation of an N-despropyl precursor with [11C]propyl iodide and of an O-desmethyl precursor with [11C]methyl iodide and was evaluated for the potential as a tracer for mapping sigma 1 receptors in the CNS and peripheral organs by PET. Following i.v. injection of [N-propyl-11C]NE-100 or [O-methyl-11C]NE-100 into mice, the two tracers showed similar tissue distribution patterns except for the liver and brain. With the coinjected carrier NE-100 or haloperidol, the uptake of [N-propyl-11C]NE-100 by the liver, pancreas and spleen was significantly decreased at 15 min after injection, whereas the effect was not significant for [O-methyl-11C]NE-100. The coinjection of NE-100 enhanced the brain uptake of the two tracers. Haloperidol also enhanced the brain uptake of [N-propyl-11C]NE-100, but not that of [O-methyl-11C]NE-100. The regional brain distribution assessed with [O-methyl-3H]NE-100 was consistent with the distribution pattern of the sigma receptors. Four sigma drugs reduced the regional brain uptake of [O-methyl-3H]NE-100 to 70%-90% of the control. In an ex vivo autoradiographic study of the rat brain, the uptake of [O-methyl-11C]NE-100 was blocked by carrier NE-100 or haloperidol (53%-59% of the control in the cortex), which suggests a receptor-specific distribution. These results show that [O-methyl-11C]NE-100 has limited potential as a PET ligand for mapping sigma 1 receptors in the peripheral organs and the CNS because of high nonspecific binding.

Animals↗
PubMed1998

PACAP increases the cytosolic Ca2+ concentration and stimulates somatodendritic vasopressin release in rat supraoptic neurons.

Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity and its receptor mRNA have been reported in the supraoptic and the paraventricular nucleus (SON and PVN, respectively) and PACAP has been implicated in the regulation of magnocellular neurosecretory cell function. To examine the site and the mechanism of the action of PACAP in the neurosecretory cells, we measured AVP release from SON slice preparations and the cytosolic Ca2+ concentration ([Ca2+]i) from single dissociated SON neurons. PACAP at concentrations from 10(-12) to 10(-7) M increased [Ca2+]i in dissociated SON neurons in a dose-dependent manner. The patterns of the PACAP-induced [Ca2+]i increase were either sustained increase or cytosolic Ca2+ oscillations. PACAP (10[-7] M) increased [Ca2+]i in 27 of 27 neurons and glutamate (10[-4] M) increased [Ca2+]i in 19 of 19 SON neurons examined, whereas angiotensin II (10[-7] M) increased [Ca2+]i in only 15 of 60 SON neurons examined. PACAP at lower concentrations (10[-10] to 10[-8] M) increased [Ca2+]i in 70-80% of neurons examined. Although the onset and recovery of the PACAP-induced [Ca2+]i increase were slower than those observed with glutamate, the spatial distribution of the [Ca2+]i increases in response to the two ligands were similar: [Ca2+]i increase at the proximal dendrites was larger and faster and that at the center of the soma was smaller and slower. The PACAP-induced [Ca2+]i responses were abolished by extracellular Ca2+ removal, the L-type Ca2+-channel blocker, nicardipine, or by replacement of extracellular Na+ with N-methyl D-glucamine, and were partially inhibited by the Na+-channel blocker, tetrodotoxin. The N-type Ca2+-channel blocker, omega-conotoxin GVIA did not significantly inhibit the PACAP-induced [Ca2+]i responses. Furthermore, PACAP (10[-7] M) as well as glutamate (10[-4] M) increased AVP release from SON slice preparations, and extracellular Ca2+ removal or nicardipine inhibited the AVP release in response to PACAP. These results indicate that PACAP enhances Ca2+ entry via voltage-gated Ca2+ channels and increases [Ca2+]i, which, in turn, stimulates somatodendritic vasopressin release by directly activating PACAP receptors on SON neurons. The results also suggest that PACAP in the SON may play a pivotal role in the control of the neurohypophyseal function at the level of the soma or the dendrites.

Angiotensin II↗
PubMed1998

Patch-clamp analysis of the mechanism of PACAP-induced excitation in rat supraoptic neurones.

In neurosecretory cells of the supraoptic nucleus (SON) of rats, pituitary adenylate cyclase activating polypeptide (PACAP) causes an increase in [Ca2+]i, and stimulates somatodendritic vasopressin (VP) release. In this report, to elucidate the ionic mechanism of the action of PACAP, membrane potentials and ionic currents were measured from SON neurones in slice preparations or from dissociated SON neurones. In the current clamp mode, PACAP depolarized membrane potentials of both phasic and non-phasic neurones and increased the firing rate. Moreover, simultaneous measurements of membrane potentials and [Ca2+]i revealed that the membrane depolarization correlated well with increases in [Ca2+]i. In the voltage-clamp mode, PACAP induced inward currents at a holding potential of -70 or -80 mV in a dose-dependent manner and the time course of the currents was similar to that of the PACAP-induced membrane depolarization. The averaged reversal potential of the PACAP-induced currents obtained from dissociated SON neurones was -33 mV, which was close to the reversal potential of non-selective cation currents in SON neurones. The currents were rapidly and reversibly inhibited by a cation-channel blocker, gadolinium. Analysis of synaptic inputs into SON neurones in slice preparations revealed that PACAP had little or no effects on the frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results suggest that pituitary adenylate cyclase activating polypeptide (PACAP) activates PACAP receptors in the postsynaptic membrane of the supraoptic nucleus (SON) neurones, and that the activation of PACAP receptors leads to opening of non-selective cation channels, depolarization of the membrane potential, and increase in the firing rate in SON neurones. Such mechanisms may account for the PACAP-induced increase in [Ca2+]i and vasopressin (VP) release observed in SON neurones.

Adenylyl Cyclases↗
PubMed1998

Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor ligand.

UNLABELLED: The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a receptors in the central nervous system (CNS). METHODS: The regional brain distribution of [11C]KF17837 and the effect of adenosine antagonists on the distribution were measured in mice by the tissue sampling method. In rats, the regional brain uptake of [11C]KF17837 and the effect of carrier KF17837 was visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was performed by PET. RESULTS: In mice, a high uptake of [11C]KF17837 was found in the striatum in which A2a receptors were highly enriched. The uptake was decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1 antagonist KF15372. In the rat brain, [11C]KF17837 was accumulated higher in the striatum than in other brain regions, and the uptake was blocked by co-injection of carrier KF17837. In a monkey PET study, a high striatal uptake of radioactivity was observed. CONCLUSION: Carbon-11-KF17837 binds to adenosine A2a receptors in the striatum. However, the presence of an unknown but specific binding site for xanthine-type compounds also was suggested in the other brain regions. The results also suggested that the in vivo receptor-binding sites of xanthine-type ligands are slightly different from those of nonxanthine-type A2a antagonists.

Animals↗
PubMed1997

Effects of reserpine treatment on the dopamine receptor binding of [3H/11C]nemonapride in the mouse and rat brain.

We investigated the effect of reserpine treatment on the striatal uptake of a radiolabeled dopamine D2-like receptor ligand nemonapride (NEM). In mice, the uptake of the [3H]NEM in the striatum, cortex and cerebellum was enhanced by the reserpine pretreatment. Neither the ratio of striatum to cerebellum nor that to cortex was affected by the reserpine pretreatment. In rats, ex vivo autoradiography showed no effect of the reserpine treatment on the striatal uptake of [11C]NEM or the striatum to cortex ratio. The results suggest that the receptor binding of NEM was not significantly influenced by reserpine-induced depletion of endogenous dopamine probably because of its high affinity for the receptors.

Animals↗
PubMed1997

Inhibin is involved in the suppression of FSH secretion in the growth phase of the dominant follicle during the early luteal phase in cows.

This study was carried out to examine the involvement of inhibin in the regulation of FSH secretion during the growth phase of the dominant follicle in the early luteal phase of cows. Six cows were given a single i.v. bolus injection of 100 ml inhibin antiserum raised against bovine 32-kDa inhibin in a castrated male goat, and five animals received the same amount of castrated male goat serum (control serum) on Day 5 of the estrous cycle (Day 0 = estrus). All animals in each group experienced a wave of follicular development after ovulation, and the dominant follicle was over 8.5 mm in diameter on Day 5. The corpus luteum was identified for each group on Day 5. Plasma concentrations of estradiol and progesterone gradually increased after ovulation and reached around 3.7 pg/ml and 3.0 ng/ml on Day 5, respectively, suggesting that the dominant follicle and corpus luteum were functional. Administration of inhibin antiserum produced a clear increase (P < 0.001) in plasma FSH within 8 hr compared with that in control animals. Plasma levels of luteizing hormone showed a moderate increase during 40 hr after the injection of antiserum (P = 0.08). A large number of antral follicles (4 mm in diameter) developed after the hypersecretion of FSH, coupled with the rise in plasma estradiol levels. These results clearly demonstrated that inhibin neutralization during the early luteal phase produces hypersecretion of FSH with a coincident stimulation of follicular development, indicating that inhibin is an important factor for the negative regulation of FSH secretion during the early luteal phase when secretion of estradiol and progesterone are normally high.

Analysis of Variance↗
PubMed1997

Evaluation of carbon-11 labeled KF15372 and its ethyl and methyl derivatives as a potential CNS adenosine A1 receptor ligand.

We prepared [11C]KF15372 ([1-propyl-11C]8-dicyclopropylmethyl-1,3-dipropylxanthine, refs 10, 13) as well as its 11C-ethyl and 11C-methyl derivatives ([11C]EPDX and [11C]MPDX), and examined the potential of the three compounds as PET ligands for CNS adenosine A1 receptors. The three compounds had high affinity for the A1 receptors in vitro in the following order; [11C]EPDX > [11C]KF15372 > [11C]MPDX. In mice, the highest initial brain uptake was found in [11C]MPDX followed by [11C]EPDX and [11C]KF15372, but the level of [11C]MPDX decreased faster than those of the other two compounds. The uptake of each compound was decreased by carrier KF15372, but not by an A2A antagonist, indicating the selective affinity for the A1 receptors. Autoradiography with [11C]MPDX ex vivo demonstrated decreased A1 receptor binding in the superior colliculus of rats deprived of retino-collicular fibers by contralateral eye enucleation. These results show that three compounds have potential as PET ligands for CNS adenosine A1 receptors.

Animals↗
PubMed1997

A novel method for counting spontaneous motor activity in the rat.

Motor activity is a good index for studying the effects of pharmacological agents. Previous investigations have measured spontaneous motor activity by counting the number of times that an animal interrupts a magnetic field or photocell beam. Quite recently, a novel activity-monitoring system, Supermex, was developed. In this system, a sensor detects the radiated body heat of an animal. The Supermex method enables an investigator to perform multi-channel measurement at low cost. Any size home cage may be used, as long as its geometry cannot block the beam's contact with the animal. Operation is very simple and sensitivity adjustment is not required after the sensor-mount position and height from the cage floor are fixed. In the present study we first used the Supermex system to examine the effects of intracerebroventricular (i.c.v.) administration of a known stimulant, thyrotropin-releasing hormone (TRH). Our results confirmed the suitability of this system for testing spontaneous motor activity. We further studied the effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and its related peptide, vasoactive intestinal polypeptide (VIP), on spontaneous motor activity.

Animals↗
PubMed1997

Ontogeny of inhibin secretion in the rat testis: secretion of inhibin-related proteins from fetal Leydig cells and of bioactive inhibin from Sertoli cells.

The ontogeny of inhibin secretion in the testis of rats was investigated. Testicular localization, content of immunoactive and bioactive inhibin and its molecular size in fetal and neonatal rats (from 16 days of gestation to 5 days of age) were determined. Strong immunostaining with an antiserum against a polypeptide of porcine inhibin alpha-subunit was noted in testicular interstitial cells from 16 days of gestation. Co-localization of inhibin alpha-subunit and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was observed in the interstitial cells until 2 days of age. Immunoreactive inhibin alpha-subunit in the interstitial tissue had disappeared by 5 days of age, although 3 beta HSD-positive cells were still detected. Weak immunostaining for the inhibin alpha-subunit was detected in the seminiferous tubules, probably in the cytoplasm of Sertoli cells, from 20 days of gestation onward. No inhibin alpha-subunit immunostaining was observed in germ cells throughout the experimental period. Testicular inhibin was detected at 16 days of gestation (49.5 +/- 6.7 pg per testis) by RIA. Testicular immunoreactive inhibin showed a tendency to increase during fetal life and levels were maintained at a similar value after birth (697.0 +/- 46.9 pg per testis at 5 days of age). Inhibin bioactivity and its molecular size in testicular homogenate was examined at 17 days of gestation and 0 and 5 days of age. Although no bioactivity was detected at 17 days of gestation, bioactivity was noted at 0 and 5 days of age (177.7 and 1303.9 pg per testis respectively). Immunoblot analysis with antiserum against inhibin alpha-subunit revealed only approximately 40 kDa molecular masses in the testis at 17 days of gestation, probably inhibin-related proteins, but not inhibin. At 0 and 5 days of age, a protein of 30 kDa molecular mass, possibly inhibin, was detected as well as material of approximately 40 kDa molecular mass. FSH in the plasma was first detected at 19 days of gestation (1197.0 ng/l), increased towards birth, and thereafter decreased (4588.5 +/- 572.3 ng/l at 21 days of gestation and 2400.0 +/- 179.6 ng/l at 5 days of age). These results indicate that Leydig cells in fetal and neonatal rats produce inhibin-related substances with no inhibin bioactivity, whereas Sertoli cells begin to produce inhibin during the perinatal period as a possible regulator of FSH secretion.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Acute appendicitis immediately after colonoscopy.

In a 69-yr-old man we treated, acute appendicitis occurred immediately after colonoscopy was performed. There were no signs or symptoms of appendicitis before colonoscopy, including in the colonoscopic findings around the cecal end and appendicular orifice. Because appendicitis is a rare complication of colonoscopy, prompt recognition should lead to early and effective treatment.

Acute Disease↗
PubMed1995

Effects of intracerebroventricular administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the motor activity and reserpine-induced hypothermia in murines.

We investigated the effects of i.c.v. administration of pituitary adenylate cyclase-activating polypeptide (PACAP) on the spontaneous motor activity and reserpine-induced hypothermia in murines. The administration of PACAP (1 or 2 nmol) caused a dose-dependent increase in both spontaneous motor activity and rearing behavior in the rat. The peptide (0.1 or 0.2 nmol) counteracted reserpine-induced hypothermia in a dose-dependent manner in mice. On the other hand, i.c.v. injection of vasoactive intestinal polypeptide, which is structurally similar to PACAP, at a dose similar to that of PACAP (2 nmol in rats, 0.2 nmol n mice) did not show a significant effect on either behavior or body temperature. Therefore, the stimulating effect of PACAP observed here may be mediated by PACAP-specific (type I) receptors. PACAP was more potent and longer-lasting than a known potent stimulating peptide, thyrotropin-releasing hormone, in both stimulating motor activity and counteracting reserpine-induced hypothermia. Results of the present study, in combination with those of previous studies identifying endogenous PACAP in the brain, suggest that PACAP may play a important role in the CNS as a stimulant in regulating motor activity and body temperature.

Animals↗
PubMed1995

Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide.

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over 16 years. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. Recently, an in vitro study has revealed that PSK is a strong inducer of cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC). To establish whether PSK has cytokine-inducing activities in vivo, we have orally administered PSK (1 g, the clinical dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone gastrectomy, and assessed the gene expression for cytokines in PBMC of each subject. As determined by the reverse-transcribed polymerase chain reaction method, the induction of gene expression for both tumor necrosis factor alpha and interleukin-8 (IL-8) was detected in PBMC from 5 of the 12 healthy volunteers (42%) and 4 of the 9 patients (44%). Furthermore, the concentration of serum IL-8 was elevated in 5 healthy volunteers given PSK orally, who had shown induction of IL-8 gene expression, as detected by enzyme-linked immunosorbent assay. These findings indicate that responsiveness of PBMC to PSK, in terms of gene expression and production of cytokines, varies among individuals. Thus, when using PSK to treat cancer patients, it seems advisable to select patients on the basis of their responsiveness to PSK. We speculate that the cytokines induced by PSK might mediate the immunoenhancing action of this agent in vivo.

Adjuvants, Immunologic↗
PubMed1995

Decrease of histone H1 kinase activity in relation to parthenogenetic activation of pig follicular oocytes matured and aged in vitro.

Changes of histone H1 kinase activity before and after electrical stimulation were connected with the ability of cytoplasm of pig oocytes to be activated parthenogenetically when matured and aged in vitro. Cumulus-oocyte complexes were collected from prepubertal gilts and cultured in a modified Waymouth's MB752/1 medium. The first mature oocytes were observed after 30 h of culture. After 36 h of culture, about 65% of oocytes had matured (reached metaphase II stage with the first polar body). When oocytes matured after 36 h of culture were stimulated with an electric pulse and subsequently cultured for 10 h, only 7% became parthenogenetically activated (formation of a female pronucleus). When oocytes matured for 60 h and 72 h underwent the same treatment, significantly more became activated parthenogenetically (46% and 57%, respectively). Oocytes matured for 72 h but not stimulated electrically also exhibited high spontaneous parthenogenetic activation (24%). Activation of oocytes resulted either in the formation of a female pronucleus(ei) or in fragmentation of oocytes. Fragmentation in stimulated and nonstimulated oocytes increased significantly after 72 h of culture (37% and 18%, respectively). Histone H1 kinase activity in immature oocytes at the germinal vesicle stage was low (17.2 fmol h-1 per oocyte). However, when oocytes were cultured for 36 and 48 h, histone H1 kinase activity increased significantly (168.2 and 138.5 fmol h-1 per oocyte, respectively). Prolonged culture (60 h and 72 h) resulted in a significant decrease in histone H1 kinase activity (94.3 and 49.3 fmol h-1 per oocyte, respectively). When oocytes cultured for up to 72 h were electrically stimulated, histone H1 kinase activity in activated oocytes (oocytes that formed a female pronucleus and fragmented oocytes) was significantly lower (24.7 mol h-1 per oocyte) than that in nonactivated oocytes (99.9 mol h-1 per oocyte). The present data clearly indicate that the gradual decrease of histone H1 kinase activity is correlated with ageing of oocytes matured in vitro and with their ability to be parthenogenetically activated.

Animals↗
PubMed1995

Proton NMR spectroscopic studies of serum as an aid to perioperative cellular metabolic monitoring.

Perioperative concentration changes of cellular metabolites in serum were studied by proton NMR spectroscopy in four cancer patients who underwent tumorectomies under general anesthesia. In proton NMR spectra of serum, the resonances assignable to fatty acid in lipoprotein, lactate, alanine, glucose, glycoprotein and other metabolites were observed. The concentrations of fatty acid and alanine did not show significant changes during the operations compared with those in healthy volunteers. The concentrations of lactate, glucose and glycoprotein increased during the operations above the concentration ranges in the control subjects. The time-course of concentration change for lactate, glucose and glycoprotein was roughly classified into two patterns: i) the maximums of lactate and glucose concentration were observed in the latter halves or at the ends of the operations; ii) the maximums of glycoprotein concentrations were observed three hours after the incision, regardless of the operative time. The results showed cellular metabolic changes became larger as the operations proceeded responding to surgical stress. Prompt cellular metabolic monitoring is indispensable for the screening of cellular metabolic disorders caused by excessive surgical stress and proton NMR spectroscopy can be a new tool for monitoring perioperative cellular metabolism.

Adult↗
PubMed1994

[The effects of H2 blockers on gastric flora and sputum culture].

Gastric juice and sputum of 12 patients, who had entered the intensive care unit postoperatively and received respiratory management, were examined for bacteria and their relationship with gastric pH was investigated. Gastric bacteria were detected in only 3 specimens out of 14 (21.4%) when the pH was under 3.5, and when the pH was above 3.5, gastric bacteria were detected in 33 specimens out of 35 (94.3%). Proliferation of gastric flora was observed as the pH increased. In 7 cases, Gram-negative bacilli (important etiologically as a cause of pneumonia) were detected. Gram-negative bacilli were also detected in sputum culture and these were found to be of the same bacteria type as those found in the gastric juice. However, no evident cases of pneumonia were observed, and proliferation of gastric bacteria did not increase the incidence of postoperative pneumonia.

Adult↗
PubMed1993

Arylsulfatase B-deficient mucopolysaccharidosis in rats.

A rat colony with mucopolysaccharidosis VI was established and the clinical, pathological, and biochemical features were characterized. Affected rats had facial dysmorphia, dysostosis multiplex, and increased urinary excretion of glucosaminoglycans (GAGs). Ultrastructural studies revealed storage of GAGs throughout the reticuloendothelial cells, cartilage, and other connective tissues, but no deposition was observed in the nervous system. Biochemical analyses demonstrated that the excreted GAG was dermatan sulfate and the activity of hepatic arylsulfatase B was < 5% of the normal mean value. Pedigree analysis showed that the phenotype was inherited as an autosomal recessive single trait. The availability of a rat model of human mucopolysaccharidosis VI should permit the development and evaluation of various strategies to treat the human disease.

Animals↗
PubMed1993

Age-related changes in blood concentrations of FSH, LH and testosterone and testicular morphology in a new rat sterile mutant with hereditary aspermia.

A new rat mutant showing aspermia was investigated. Groups of 4-7 mutant male rats were killed at 3, 5, 10, 15 and 25 weeks of age. Examination by microscope showed apparent abnormalities in the seminiferous epithelium from 3 weeks of age onward. Inclusion-like bodies were observed in the cytoplasm of pachytene spermatocytes from 3 weeks old and instead of spermiation, polynuclear giant cells were formed within the seminiferous epithelium after 5 weeks of age. Histological analysis of seminiferous epithelium of adult mutant rats also showed a marked decrease in the number of preleptotene, leptotene and pachytene spermatocytes and tubules containing only spermatogonia and Sertoli cells in the seminiferous epithelium increased with age. However, the combination of other cellular elements of germ cells in the seminiferous epithelium was similar to that in normal rats and the distribution rate of these seminiferous tubules was close to that of normal rats, indicating that cyclicity of seminiferous epithelium was still maintained in the mutant rats despite the lack of spermiation. Plasma concentrations of FSH and LH were significantly higher in the mutant male rats than in normal male rats at 5 and 10 weeks of age onward, respectively. Plasma concentrations of testosterone were lower in the mutant male rats than in normal male rats. Silastic capsules containing testosterone were implanted into the unilateral testis of adult mutant male rats and animals were autopsied 5 weeks later. However, intratesticular administration of testosterone did not affect restoration of spermatogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗