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Biomedical subjects

Y Noda

Publications and source records attributed to Y Noda.

At least 181 records · Page 10Linked to original sources
PubMed1998

Stabilization of vasoactive intestinal peptide by lipids.

An anionic phospholipid, phosphatidylglycerol (PG), induced vasoactive intestinal peptide (VIP) to adopt a helical conformation, determined by circular dichroism studies. PG inhibited the trypsin-catalyzed, antibody-catalyzed and uncatalyzed cleavage of VIP, measured by radiometric and HPLC methods. Phosphatidylcholine, a neutral lipid, did not alter the circular dichroism spectra of VIP, and it was without detectable effect on the rates of VIP cleavage. Trypsin-catalyzed cleavage of Boc-Ile-Glu-Arg-methylcoumarinamide, a substrate unrelated in sequence to VIP, proceeded at equivalent rates in the absence and presence of PG, which suggests that the phospholipid did not exert a nonspecific inhibitory effect on the enzyme. Study of the kinetics of antibody-catalyzed VIP cleavage indicated that the inhibition by PG was due to decreased affinity for VIP, suggested by observations of increased K(m) values and unaltered Vmax values. Incorporation of VIP in the liposomes and the liposomal surface permitted maintenance of the peptide in essentially undegraded form at 37 degrees C for 8 days. The longevity of liposomal VIP administered i.v. to mice was increased by about 5-fold compared with aqueous VIP. These observations indicate that certain phospholipids and liposomes can be applied to circumvent the rapid loss of VIP in vitro and in vivo due to degradative processes.

Amino Acid Sequence↗
PubMed1998

Involvement of dopaminergic system in phencyclidine-induced place preference in mice pretreated with phencyclidine repeatedly.

In the conditioned place preference test, phencyclidine (PCP) produces place aversion in naive rats, whereas PCP produces place preference in rats treated with PCP repeatedly. Although the PCP-induced place aversion is thought to involve the serotonergic system, the mechanisms of the PCP-induced place preference are unclear. We investigated whether the dopaminergic system is involved in place preference induced by PCP in mice repeatedly treated with PCP, because it is well known that the dopaminergic system plays an important role in the rewarding effect of drugs. PCP (2-8 mg/kg s.c.) induced a dose-dependent place aversion in naive mice, whereas PCP (2-8 mg/kg s.c.) induced a dose-dependent place preference in mice pretreated with PCP (10 mg/kg/day s.c.) for 28 days. The place preference induced by PCP (8 mg/kg s.c.) was attenuated significantly by alpha-methyl-rho-tyrosine (100 mg/kg i.p.), a tyrosine hydroxylase inhibitor, 6-hydroxydopamine (100 micrograms/mouse i.c.v.), a dopaminergic neurotoxin, and R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zepine (0.5 mg/kg s.c.), a dopamine D1 receptor antagonist. These agents themselves produced neither the place preference nor aversion. In contrast to the attenuating effects of these agents, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (30 mg/kg i.p.), a noradrenergic neurotoxin, ritanserin (1 mg/kg i.p.), a serotonin2 receptor antagonist, and (-) sulpiride (50 and 100 mg/kg i.p.), a dopamine D2 receptor antagonist, failed to affect the PCP-induced place preference. In mice pretreated with methamphetamine (1 mg/kg/day s.c.) for 14 days, PCP (8 mg/kg s.c.) induced the place preference, but not aversion. These results demonstrate that the PCP-induced place preference depends on dopaminergic, but not on serotonergic and noradrenergic, neuronal systems and suggest a role for D1 receptors in the mediation of the PCP-induced place preference.

Animals↗
PubMed1998

[Rehabilitation approach to children with sequelae of hypoxic encephalopathy].

We studied the rehabilitation approach to children with acquired hypoxic encephalopathy. The subjects were 13 children with sequelae of hypoxic encephalopathy. The onset ranged from 1 month to 15 years of age. Recovery was good in no case, moderate in 3, poor in 3, and absent in 7 cases. We evaluated the following factors: condition at the onset, present status, degree of improvement of the functional independence measure (FIM). In the moderate recovery group, resuscitation was performed within 5 minutes, and consciousness loss disappeared within 3 days. Some patients had no physical disability, whereas others had ataxia. In the no recovery group, consciousness loss was severe and continued more than 5 days. Most of them had spastic quadriplegia. The improvement of FIM was 52.8 +/- 23.9 in the moderate recovery group, 12.0 +/- 8.2 in the poor recovery group, and 0 in the no recovery group. Pediatricians as well as rehabilitation doctors should use FIM to evaluate the effect of rehabilitation.

Activities of Daily Living↗
PubMed1997

Identification and classification of 16 new kinesin superfamily (KIF) proteins in mouse genome.

KIF (kinesin superfamily) proteins are microtubule-dependent molecular motors that play important roles in intracellular transport and cell division. The extent to which KIFs are involved in various transporting phenomena, as well as their regulation mechanism, are unknown. The identification of 16 new KIFs in this report doubles the existing number of KIFs known in the mouse. Conserved nucleotide sequences in the motor domain were amplified by PCR using cDNAs of mouse nervous tissue, kidney, and small intestine as templates. The new KIFs were studied with respect to their expression patterns in different tissues, chromosomal location, and molecular evolution. Our results suggest that (i) there is no apparent tendency among related subclasses of KIFs of cosegregation in chromosomal mapping, and (ii) according to their tissue distribution patterns, KIFs can be divided into two classes-i.e., ubiquitous and specific tissue-dominant. Further characterization of KIFs may elucidate unknown fundamental phenomena underlying intracellular transport. Finally, we propose a straightforward nomenclature system for the members of the mouse kinesin superfamily.

Amino Acid Sequence↗
PubMed1997

Effects of antidepressants on phencyclidine-induced enhancement of immobility in a forced swimming test in mice.

We have previously found that repeated phencyclidine (PCP) treatment enhances the immobility induced by forced swimming and suggested that this behavioral change could be used as a model of the negative symptoms, particularly depression, of schizophrenia. The present study attempted to examine the effects of antidepressants on the depressive states (immobility) induced by forced swimming in mice repeatedly treated with PCP, compared with those in mice repeatedly treated with saline. In mice repeatedly treated with saline, desipramine (5 and 10 mg/kg) and imipramine (5 and 10 mg/kg) significantly attenuated immobility, whereas mianserin (5-20 mg/kg) and clomipramine (10 and 50 mg/kg) had no affect. In mice repeatedly treated with PCP, the enhancing effect of PCP on immobility was attenuated by mianserin (5-20 mg/kg) at doses which did not have any effect in saline-treated mice, and by desipramine at higher doses (20 and 50 mg/kg). However, imipramine (5-20 mg/kg) and clomipramine (10-50 mg/kg) did not affect PCP-induced enhancement of immobility. In the biochemical study, the content of 5-hydroxyindoleacetic acid (5-HIAA) and the 5-HIAA/5-hydroxytryptamine (5-HT) ratio in the prefrontal cortex in mice repeatedly treated with PCP, but not with saline, following the forced swimming test were significantly increased, compared with those in the corresponding control mice (which did not perform the test). The present findings suggest that the depressive states induced by the forced swimming in mice repeatedly treated with PCP are less sensitive to acute treatment with tricyclic antidepressants, and this may be due to increase in 5-HT turnover. Antidepressants such as mianserin, which have the 5-HT2 receptor antagonist properties, may be useful for the treatment of negative symptoms of schizophrenia.

Animals↗
PubMed1997

Unrestrained nociceptive response and disregulation of hearing ability in mice lacking the nociceptin/orphaninFQ receptor.

In the G-protein-coupled receptor superfamily, the opioid receptor subfamily is constituted of the three distinct opioid receptors (namely delta-, mu- and kappa-subtypes) and the receptor for nociceptin (also designated orphaninFQ). The members of the opioid receptor subfamily were known to mediate a variety of cellular inhibitory effects. The three opioid receptors are known to play central roles in mediating analgesia and many other physiological activities; however, the nociceptin receptor was identified recently and less is known about its physiological roles. Here we report the generation and characterization of mice lacking the nociceptin receptor. The knockout mice showed no significant differences in nociceptive threshold and locomotor activity compared with control mice, but they lost nociceptin-induced behavioral responses. These results indicate that the nociceptin system is not essential for regulation of nociception or locomotor activity. On the other hand, we found insufficient recovery of hearing ability from the adaptation to sound exposure in the mutant mice. Thus, the nociceptin system appears to participate in the regulation of the auditory system.

Animals↗
PubMed1997

Cloning of apg-2 encoding a novel member of heat shock protein 110 family.

Chinese hamster heat shock protein 110-encoding gene (hsp110), mouse apg-1 and human hsp70RY are structurally related genes, with the first two encoding about 110-kDa HSPs [Yoon et al. (1995) J. Biol. Chem. 270, 15725-15733; Kaneko et al. (1997) J. Biol. Chem., in press; Fathallah et al. (1993) J. Immunol. 151, 810-813]. Using apg-1 cDNA as a probe, we isolated a novel cDNA, apg-2 from a mouse testis cDNA library, which was highly homologous to human hsp70RY. However, the predicted amino acid (aa) sequence of APG-2 was longer (841 aa) than that of HSP70RY (701 aa) and comparable to those of HSP110 and APG-1. Northern blot analysis revealed that the expression of apg-2 transcripts was ubiquitous in various mouse tissues, and most abundant in the testis and ovary. While induction of hsp70 transcripts was observed in mouse TAMA26 Sertoli cells and NIH/3T3 fibroblasts on temperature shift from 37 degrees C to 42 degrees C (traditional heat shock) or from 32 degrees C to 39 degrees C, apg-2 transcripts were not induced under either condition. These results suggest that apg-2 is an isoform of mouse homolog of hsp70RY, but that it belongs to the hsp110 family instead of hsp70 family, and that it plays a role under non-stress conditions.

Amino Acid Sequence↗
PubMed1997

Developmentally regulated expression of APG-1, a member of heat shock protein 110 family in murine male germ cells.

Apg-1 encodes a heat shock protein belonging to the heat shock protein 110 family, and is inducible by a 32 degrees C to 39 degrees C heat shock. Northern blot analysis of the testis from immature and adult mice, and of the purified germ cells revealed the quantitative change of the apg-1 transcripts during germ cell development. By in situ hybridization histochemistry the expressions of the apg-1 transcripts were detected in germ cells at specific stages of development including spermatocytes and spermatids. Although heat-induction of the apg-1 transcripts was observed in W/Wv mutant testis lacking germ cells, it was not detected in wild-type testis nor in the purified germ cells. Thus, the apg-1 expression is not heat-regulated but developmentally regulated in germ cells, suggesting that APG-1 plays a role in normal development of germ cells.

Animals↗
PubMed1997

Role of (+)-SKF-10,047-sensitive sub-population of sigma 1 receptors in amelioration of conditioned fear stress in rats: association with mesolimbic dopaminergic systems.

Rats exhibited a marked suppression of motility when they were re-placed in the same environment as that in which they had previously received an electric footshock. We examined the behavioral and neurochemical effects of (+)-N-allylnormetazocine hydrochloride ((+)-SKF-10,047) and (+)-pentazocine, putative sigma 1 receptor ligands, on this psychological-stress-induced motor suppression, defined as a conditioned fear stress. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently attenuated the conditioned fear stress, whereas (+)-pentazocine failed to do so even at a higher dose (32 mg/kg). In rats showing the conditioned fear stress, dopamine turnover (i.e., the ratio of dopamine metabolites/dopamine contents) was decreased in the nucleus accumbens and was increased in the medial prefrontal cortex, but remained unchanged in the striatum. (+)-SKF-10,047 (3 and 6 mg/kg) dose-dependently reversed the decreased dopamine turnover in the nucleus accumbens without changing the increased dopamine turnover in the medial prefrontal cortex. (+)-Pentazocine (32 mg/kg) did not affect the stress-induced changes in dopamine turnover in these brain regions. Thus, the decreased dopamine turnover in the nucleus accumbens appears to be involved in the conditioned fear stress. These results suggest that (+)-SKF-10,047 ameliorates the conditioned fear stress by reversing the psychological stress-induced dysfunction in the mesolimbic dopaminergic systems, and that the (+)-SKF-10,047-sensitive sub-population of sigma 1 receptors may play in important role in this stress response.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

A two-dimensional NMR study of exchange behavior of amide hydrogens in a lysozyme derivative with an extra cross-link between Glu35 and Trp108--quenching of cooperative fluctuations and effects on the protein stability.

Two-dimensional nmr spectra [correlated spectroscopy (COSY), homonuclear Hartmann-Hahn (HOHAHA), nuclear Overhauser effect spectroscopy (NOESY)] have been observed for cross-linked lysozyme, a chemically modified lysozyme derivative with an extra ester cross-link between residues E35 and W108. Eight shifted cross-peaks were found in the fingerprint region of COSY spectra. By searching COSY, HOHAHA and NOESY spectra, they have been assigned to A32, E35, S36, 158, A107, W108, V109, and A110. The NOE connectivities (dNN and d alpha N) found for the cross-linked lysozyme are quite similar to those for the intact lysozyme. Exchange behavior of amide hydrogens has been studied for both intact and cross-linked lysozymes by observing the fingerprint region of COSY spectra. Hydrogen exchange reactions were carried out at pH 7.0 and at several temperatures. There exist 41 amide hydrogens whose exchange reactions are detectable under this experimental condition. Not only exchange rates but also their activation enthalpies were determined for individual amide hydrogens. They are classified into two groups, which are called categories III and IV. Category III hydrogens are distributed in relatively flexible peripheral parts of protein, and category IV hydrogens are deeply buried in the core region of protein. Category III hydrogens are exchanged through localized unfolding around their sites with a low activation enthalpy ranging from 10 to 25 kcal/mol. The formation of an extra cross-link affects neither the exchange rate nor the activation enthalpy of category III hydrogens. However, amide hydrogens of residues 34-39 in the vicinity of the hinge are exceptions. They are easily exchanged in the intact lysozyme but their exchange rates are drastically retarded by cross-linking. In the intact lysozyme, structural fluctuations mediating the exchange of category IV hydrogens are highly cooperative with a large activation enthalpy. These large-scale structural fluctuations are the global unfolding of the overall structure and also concerted motions within a domain. Especially near 38 degrees C, it was found that the dominant fluctuation occurring in the alpha-domain is different from that in the beta-domain. However, these concerted motions are strongly quenched by the formation of the cross-link because of the cooperativity of such a large-scale fluctuation. The stabilization of a localized area of protein by cross-linking results in the great suppression of large-scale and concerted motions. The exchange rates of category IV hydrogens are extremely retarded in the cross-linked lysozyme, so that they are exchanged through the so-called penetration mechanism characterized by a low activation enthalpy. These experimental results are discussed with regard to the contribution of cross-linking to the stabilization of the folded structure of protein.

Cross-Linking Reagents↗
PubMed1997

Superficial elevated-type early gallbladder carcinoma treated by laparoscopic cholecystectomy.

A 60-year-old woman was admitted to our department for detailed examination of a polypoid lesions of the gallbladder detected at the time of a mass survey by ultrasound. Endoscopic ultrasonography (EUS) demonstrated a broad-based mass lesion, about 10 mm in size, with an irregular surface, at the peritoneal side of the body of the gallbladder. The layer structure of the gallbladder wall had not been destroyed by the mass. Computed tomography showed no direct invasion of the liver or other evidence of metastasis. Type-IIa (superficial elevated-type) early gallbladder cancer was suspected and laparoscopic cholecystectomy was performed. Histologically, the tumor proved to be a papillo-tubular adenocarcinoma, 9 x 8 mm in size, confined to the mucosa and without lymphatic permeation, vascular involvement, perineural invasion, or other signs of metastasis. Laparoscopic cholecystectomy for gallbladder cancer can be indicated only when a lesion is a pedunculated protruded-type (type-Ip) cancer, or a broad-based cancer 10 mm or less in size located on the peritoneal side with no destruction of the layer structure of the wall demonstrated by EUS. This strategy is justified only with precise evaluation of the lesion by EUS.

Adenocarcinoma↗
PubMed1997

Role of nitric oxide in the effect of aging on spatial memory in rats.

Since there is evidence that nitric oxide (NO) plays an important role as a diffusible messenger in learning and memory, we examined the role played by NO in the effect of aging on spatial memory in rats. The performance of aged rats (30 months old) in a radial-arm maze task was significantly impaired compared to that of adult rats (3 months old). The number of neurons containing NADPH-diaphorase (NADPH-d) reactivity in the cerebral cortex and striatum of aged rats was significantly less than that in the adult rats. The daily administration of NG-nitro-L-arginine methyl ester (L-NAME; 10-60 mg/kg, i.p.) resulted in a dose-dependent impairment of acquisition in the radial-arm maze task, while it failed to affect previously acquired performance, i.e., retention, in the adult rats. The content of 5-hydroxyindoleacetic acid in the hippocampus and of 3,4-dihydroxyphenylacetic acid in the striatum was significantly decreased and increased, respectively, in the L-NAME (60 mg/kg/day)-treated adult rats compared with that in controls. These findings demonstrate that NO production in the brain may be decreased in aged rats, suggesting that this alteration may be involved in memory processes, especially in the acquisition, but not in the retention, of spatial learning in rats, and further, that endogenous NO may be involved in the regulation of dopamine and 5-hydroxytryptamine metabolism.

Aging↗
PubMed1997

A synergistic interaction between dopamine D1 and D2 receptor subtypes in the memory impairments induced by concussive brain injury (CBI) in mice.

Profound latent learning and memory deficits with increased monoamine levels in the brain following concussive brain injury (CBI) have been documented in our previous work. The purpose of the present study was to determine the role of dopamine (DA) receptor subtypes in the memory deficits associated with CBI. Profound latent learning and memory impairments were observed in the vehicle-treated CBI mice. SCH-23390 administered 15 min post-injury had no significant effects on the impairments of latent learning and memory in the CBI mice. Sulpiride significantly improved the impairments of latent learning and memory in a dose-dependent manner, indicating that activation of dopaminergic neuronal function is involved in the CBI-induced amnesia. Interestingly, co-administration of sulpiride and SCH-23390, at doses which alone has no significant effect, significantly ameliorated the impairments of latent learning and memory. These results strongly suggested that D1 and D2 receptor subtypes are synergistically involved in the dysfunction of learning and memory associated with CBI.

Animals↗
PubMed1997

(+)-Eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a putative cognitive enhancer, facilitates recovery from concussive brain injury-induced learning and memory impairments in mice.

We characterized alterations in the ability of concussive brain injury (CBI) models to perform a water-finding task and examined effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel apovincaminic acid derivative, on post-traumatic impairments in latent learning and memory processes. Two types of CBI-induced amnesia (retrograde and anterograde) were produced by means of post- or preacquisition head impact using a simple weight-drop device. Profound impairments of latent learning and memory processes related to retention and retrieval were observed in the CBI mice. In the CBI-induced retrograde amnesia model, VA-045 (0.5-4.0 mg/kg) significantly ameliorated impairments of latent learning and retention in both the retention test and the retest. In the CBI-induced anterograde amnesia model, the protective effects of the compound on impairments in latent learning and retention or retrieval were significant in both the retention test and the retest. These results suggested that VA-045 may be a novel cognitive enhancer for attenuating or protecting against the learning and memory dysfunction associated with CBI.

Amnesia, Retrograde↗
PubMed1997

The effect of the loss of molar teeth on spatial memory and acetylcholine release from the parietal cortex in aged rats.

It has been demonstrated that a loss of teeth is a troublesome problem among age-related pathological phenomena of the oral cavity, which influences the entire body, due to the impairment of mastication. The present studies investigated the abilities of learning and memory and acetylcholine (ACh) release in the parietal cortex in aged rats without molar teeth (hereafter referred to as 'teethless'). After the molar teeth of rats were extracted, the rats were fed with powdered food for 135 weeks. Although the performance in the radial arm maze was progressively acquired by daily training, an increase in the number of errors and a decrease in the initial correct responses were observed in the teethless aged rats compared to the control aged rats, indicating impaired acquisition of spatial memory in the teethless aged rats. The basal level of extracellular ACh in the parietal cortex was not different between the teethless aged rats and the control aged rats. However, the extracellular ACh level of the teethless aged rats under high-concentration of K+ and atropine sulfate stimulation was significantly low compared to that of the control aged rats. These results suggest that the impairment of spatial memory in the teethless aged rats may be due to the functional deterioration of the cholinergic neuronal system induced by tooth loss and that there is a possibility that the loss of teeth may be one of the risk factors for senile dementia.

Acetylcholine↗
PubMed1997

A case report of carotid body tumor.

A case of left carotid body tumor is presented. A 47-year-old female patient consulted our otorhinolaryngological clinic with a neck swelling that had persisted for 5 months. On physical examination, a movable and pulsating hard mass measuring 2 x 2.5 cm in size was found on the left side of her neck, near the angle of the mandible. Computed tomography, magnetic resonance image and angiography all demonstrated a well-circumscribed tumor mass showing high vascularity and located at the bifurcation of the left carotid artery. The tumor involved the left carotid artery, but the patency of the artery was preserved. The patient showed satisfactory temporary balloon occlusion test results without neurological complications. Since the tumor was strongly adherent to the carotid arterial wall, the tumor was resected together with the carotid artery. Histologically, the tumor was composed of organoid clusters of round cells with eosinophilic granular cytoplasm. Involvement of tumor cells was seen to the adventitia of the carotid artery, but only slight cellular atypia was seen. Ultrastructurally, two types of cells were observed in the central and marginal portion of the tumor; these were round chief cells with few cytoplasmic neurosecretory granules and spindle-shaped sustentacular cells. Immunohistochemically, the chief cells and sustentacular cells showed positive reaction for neuron-specific enolase and S-100, respectively. The ultrastructural findings suggested the benign nature of the tumor.

Biomarkers, Tumor↗