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Biomedical subjects

H Maeno

Publications and source records attributed to H Maeno.

At least 19 recordsLinked to original sources
PubMed2001

Mouse neurotensin receptor 2 gene (Ntsr2): genomic organization, transcriptional regulation and genetic mapping on chromosome 12.

We earlier isolated and characterized the mouse neurotensin receptor 1 (Ntsr1) gene and developed Ntsr1 null mice. In the present study, we isolated the mouse neurotensin receptor 2 gene (Ntsr2) and characterized the structure. The gene fragments available to us have 1.1 kb of 5' upstream promoter region and a 7 kb coding region composed of four exons. Transcription initiation sites, determined by primer extension analysis, are located at 286 and 303 bp upstream from initiation of the ATG codon. The promoter region contains a TATA-like box, a typical CAAT box and putative GATA-2, CREB, Oct-2 and Ikarous 2 binding elements. We also found novel splice donor-acceptor sites for alternative splicing, which could generate a short form of mRNA encoding a truncate-type receptor. In addition, we determined the chromosomal location of the Ntsr2 gene and mapped it at 6 cM from the centromere on chromosome 12.

Alternative Splicing↗
PubMed1997

Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.

Mammalian bombesin-like peptides are widely distributed in the central nervous system as well as in the gastrointestinal tract, where they modulate smooth-muscle contraction, exocrine and endocrine processes, metabolism and behaviour. They bind to G-protein-coupled receptors on the cell surface to elicit their effects. Bombesin-like peptide receptors cloned so far include, gastrin-releasing peptide receptor (GRP-R), neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). However, despite the molecular characterization of BRS-3, determination of its function has been difficult as a result of its low affinity for bombesin and its lack of an identified natural ligand. We have generated BRS-3-deficient mice in an attempt to determine the in vivo function of the receptor. Mice lacking functional BRS-3 developed a mild obesity, associated with hypertension and impairment of glucose metabolism. They also exhibited reduced metabolic rate, increased feeding efficiency and subsequent hyperphagia. Our data suggest that BRS-3 is required for the regulation of endocrine processes and metabolism responsible for energy balance and adiposity. BRS-3-deficient mice provide a useful new model for the investigation of human obesity and associated diseases.

Adipose Tissue, Brown↗
PubMed1997

Generation and characterization of mice lacking gastrin-releasing peptide receptor.

Gastrin-releasing peptide (GRP) is a mammalian bombesin-like peptide which is widely distributed in the central nervous system as well as in the gastrointestinal tract. GRP binds to its high affinity receptor (GRPR) to elicit a wide spectrum of biological effects on behavior, digestion, and metabolism. To define the in vivo function of GRPR, we generated GRPR null mutant mice by gene targeting. The intracerebroventricular administration of GRP caused hypothermia in wild-type mice, but not in mutant mice. The GRPR deficient mice showed significantly increased locomotor activity during the dark period, and social responses scored by sniffing, mounting, and approaching behaviors against an intruder. Aggressive scores such as fighting and biting were not altered in the mutant mice. These phenotypes were observed in mice generated from two independent ES cell clones and backcrossed to a C57BL/6J background. The GRPR deficient mice should be useful for studying the bombesin system in vivo.

Animals↗
PubMed1997

[The meaning of eat in home patients with end-stage cancer].

When a patient difficult to eat, he will not be only malnutrition, but loses a volition of his life and falls into depression. This time, we present a patient with relapse advanced pharynx cancer, who could not ingestion. Therefore she had said "DEATH". She tried eagerly rehabilitation of ingestion, swallowing and breathing, and she was able to eat again and could be positive posture. Ingestion is very important for human, and the patient found a meaning of her life and she was able to take home care nursing.

Deglutition Disorders↗
PubMed1996

Cloning and characterization of the rat neurotensin receptor gene promoter.

The 5'-terminal region of the rat neurotensin receptor (NTR) gene was isolated and characterized. Genomic Southern analysis revealed that the NTR gene occurs as a single copy in the rat haploid genome. The upstream putative promoter region did not contain canonical TATA or CAAT boxes but has a consensus sequence for the transcription factor Sp1. This promoter is embedded in a large G + C-rich domain with characteristics of an CpG island. Transfection experiments using neurotensin receptor-luciferase fusion genes demonstrated that the 5'-flanking sequence functions as a strong promoter in the NG-108-15 cell. Deletion analysis suggested the presence of a core promoter (-470 to -662) that drives the minimal expression of the NTR gene.

Animals↗
PubMed1995

Genomic structure of the mouse gene (Lmnb1) encoding nuclear lamin B1.

The mouse gene (Lmnb1) that encodes nuclear lamin B1 was isolated. Structural analyses revealed that the lamin B1 gene spans about 43 kb of the genome and consists of 11 exons and 10 introns. Exon/intron structure of the B1 gene clearly showed the conserved organization shared among the intermediate filament protein family genes. The presumptive promoter region has high GC content and contains a CAAT box and multiple SP1 sites but no classical TATA box, suggesting that the lamin B1 gene has a typical housekeeping gene promoter with a CpG island. These data reveal the gene structure of the only remaining unanalyzed mouse somatic lamin gene. Gene structures of all the mouse somatic lamins are compared.

Amino Acid Sequence↗
PubMed1995

Regulation of mRNA expression involved in Ras and PKA signal pathways during rat hypoglossal nerve regeneration.

Using in situ hybridization histochemistry and immunohistochemistry, the present study examines the cooperative regulation of transcription of molecules involved in the Ras-signal and the cAMP dependent protein kinase (PKA) pathways during peripheral nerve regeneration in rats. Injury to hypoglossal motor neurons resulted in an increase in extracellular regulated kinase (ERK, or MAP kinase) and ERK kinase (MEK, or MAP kinase kinase) mRNAs, but in a decrease in the expression of the catalytic subunits of PKA (C alpha and C beta) mRNAs. These results show the importance of the Ras-signal pathway in the nerve regeneration process and extend recent observation which suggested a cross-talk between the Ras and PKA pathways in vitro. The down-regulation of PKA may facilitate the activation of the Ras pathway which is located downstream of the growth factor receptor. The present study may suggest a possibility of regulatory talk between these two major signal transduction pathways.

Animals↗
PubMed1995

Daily walking combined with diet therapy is a useful means for obese NIDDM patients not only to reduce body weight but also to improve insulin sensitivity.

OBJECTIVE: To evaluate the effects of walking combined with diet therapy (1,000-1,600 kcal/day) on insulin sensitivity in obese non-insulin-dependent diabetes mellitus (NIDDM) patients. RESEARCH DESIGN AND METHODS: Subjects were divided into two groups: 10 patients were managed by diet alone (group D), and 14 patients were placed in the diet and exercise group (group DE). Group DE was instructed to walk at least 10,000 steps/day on a flat field as monitored by pedometer (19,200 +/- 2,100 steps/day), and group D was told to maintain a normal daily routine (4,500 +/- 290 steps/day). A glucose clamp procedure at an insulin infusion rate of 40 microU.min-2.min-1 was performed before and after the 6- to 8-week training program. Mean serum insulin concentrations ranged from 720 to 790 pmol/l. RESULTS: While body weight (BW) in groups D and DE decreased significantly (P < 0.01) during the study, the amount of BW reduction in group DE was greater than that in group D (7.8 +/- 0.8 vs. 4.2 +/- 0.5 kg, P < 0.01). After training, glucose infusion rate (GIR) and metabolic clearance rate (MCR) in group D did not significantly increase; however, GIR and MCR increased significantly in group DE, from 17.21 +/- 1.11 to 26.09 +/- 1.11 mumol.kg-1.min-1 (P < 0.001) and from 3.0 +/- 0.3 to 5.3 +/- 0.4 ml.kg-1.min-1 (P < 0.001), respectively. The analysis of variance showed significant effects of exercise (time x exercise, P = 0.0005) for the improvement of MCR. Significant correlations were also observed between delta MCR and average steps per day (r = 0.7257, P < 0.005) in group DE. CONCLUSIONS: Walking, which can be safely performed and easily incorporated into daily life, can be recommended as an adjunct therapy to diet treatment in obese NIDDM patients, not only for BW reduction, but also for improvement of insulin sensitivity.

Adult↗
PubMed1994

Marginal topography of neurons expressing the substance P receptor in the rat suprachiasmatic nucleus.

Neurons expressing the substance P (SP) receptor (NK1 receptor) in the suprachiasmatic nucleus of the hypothalamus (SCN) have been topographically identified using radioactive in situ hybridization histochemistry. In the anterior hypothalamic area, clustered labeled neurons of small size and exhibiting low levels of gene expression are observed exclusively at the dorsolateral margin of the SCN, straddling cytoarchitectural boundaries of the nucleus. The marginal topography of neurons putative target of a SP-containing retinal input to the ventral SCN indicates that their dendrites bearing the receptor extend towards the retinorecipient part of the nucleus, where they can be modulated by overlapping inputs from the intergeniculate leaflet and the raphe. Eventual interactions between glutamatergic and putative tachykininergic retinal pathways for a coherent photic control of circadian rhythms may therefore occur mainly via intrinsic neuronal connections between their distinct target populations. In addition, since glutamate and SP induce electrophysiological responses in ventrolateral neurons with no interactive effect, neurons integrating both chemical signals, subsequently to their modulation by several influences, may be not located within the ventrolateral SCN. Alternatively but not exclusively, marginal neurons could be a target of SP-containing neurons within the SCN or nearby the nucleus, or from ascending projections from the raphé where serotonin and SP colocalize. The marginal topography of neurons expressing the SP receptor supports the view of the involvement of neurons located in the vicinity of the nucleus in the regulation of circadian rhythms.

Animals↗
PubMed1994

Growth factors and extracellular signal-regulated kinases (mitogen-activated protein kinase) in the rat pineal gland.

The present study revealed that the pineal gland expressed basic fibroblast growth factor (bFGF) and FGF-receptor 1 (FGFR1/flg), suggesting that bFGF in the pineal gland acts in an autocrine or paracrine manner, which is mediated by FGFR1/flg. The present study also examined gene expression of the extracellular signal-regulated kinase (ERK) family (ERK1-3) which may be intracellular signal mediators of growth factors. ERK1 [mitogen-activated protein kinase (MAP-kinase)] was strongly expressed throughout the pineal gland, while expression of ERK2 and ERK3 was not found. These findings suggest the presence of a signal pathway from bFGF to ERK1 via FGFR1/flg in the pineal gland.

Animals↗
PubMed1994

[Effects of ingestion of "BON-NARINE" on immune functions in mice].

A study was carried out to examine the effects of ingestion of "BON-NARINE" (BN) on mice immune functions. Mice aged 12 weeks were divided into 4 groups. The first group was given BN at 30 mg/kg (BN-30 group), the second group was given BN at 90 mg/kg (BN-90 group), the third group was given zymosan at 50 mg/kg (Zy group) and the fourth group was a control receiving no treatment. The mice of groups BN-30 and BN-90 were given BN p.o. at doses of 30 mg/kg and 90 mg/kg per day for 20 consecutive days, respectively. The mice of group Zy were given zymosan i.p. at a dose of 50 mg/kg per day for 2 consecutive days. The results obtained were as follows: 1) Potentiation of phagocytic function of the reticuloendothelial system, examined by the carbon clearance method, was seen in the BN-30, BN-90 and Zy groups. 2) The glucose consumption of peritoneal macrophages (M phi) increased significantly in the BN-30 and Zy groups, but not in the BN-90 group. 3) Superoxide anion (O2-) production of peritoneal M phi significantly increased in the BN-30 and Zy groups compared with the control group, but an increasing tendency was observed in the BN-90 group. 4) The acid phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH) activities of peritoneal M phi increased significantly in the BN-30, BN-90 and Zy groups. 5) The proliferation of splenocytes induced by Con A in the BN-30, BN-90 and Zy groups significantly increased compared with the control group. These results demonstrated that the ingestion of "BON-NARINE" promotes phagocytic activity in the reticuloendothelial system in mice and has a stimulatory effect on M phi because of increases in glucose consumption, O2- production, APH, GLU and LDH activities in the peritoneal M phi of mice. BN also intensified the T-cell function represented by Con A-induced splenocyte proliferation.

Animals↗
PubMed1993

Cellular localization of serotonin transporter mRNA in the rat brain.

Expression of serotonin (5-hydroxytryptamine, 5-HT) transporter mRNA in the rat brain was examined by in situ hybridization histochemistry with a synthetic oligonucleotide probe. 5-HT transporter mRNA was expressed in neurons in most of the raphe nuclei. The dorsal and median raphe nuclei contained intensely labeled neurons, while the caudal linear nucleus, raphe magnus nucleus, raphe pontis nucleus, raphe pallidus nucleus and the raphe obscurus nucleus contained weakly or moderately labeled neurons. The localization pattern of the 5-HT transporter mRNA-positive neurons coincides fairly well with that of 5-HT-immunoreactive neurons, indicating that 5-HT transporter is primarily located in serotonergic neurons.

Animals↗
PubMed1993

Differential immunocytochemical localization of GABAA receptor gamma 1 and gamma 2 subunits in the rat brain.

Subunit-specific polyclonal antisera against the GABAA receptor gamma 1 and gamma 2 subunits were raised in rabbits and used for immunoblotting and immunocytochemistry of the rat brain. Each subunit protein was differentially distributed even in the region like cerebellar cortex where mRNAs of both subunits were distributed in the same manner. This may indicate that GABAA receptor gamma 1 and gamma 2 subunit proteins are subject to a subunit-specific subcellular sorting mechanism.

Amino Acid Sequence↗
PubMed1993

Distribution of the substance P receptor (NK-1 receptor) in the central nervous system.

The overall distribution of mRNA for the substance P receptor (NK-1) was investigated in the rat brain by in situ hybridization histochemistry using synthetic oligonucleotide probes. The NK-1 positive cells were distributed throughout the brain. Among the positive cells an intense hybridization signal was observed in the basal ganglia and the dorsal tegmental areas. In the hippocampus, hypothalamus, midbrain, and medulla oblongata, weak to moderate positive signal were recorded in various areas. Comparing our results with those of previous workers on the localization of substance P using both immunohistochemistry and in situ hybridization various relationships between the ligand and its receptor localization were characterized. Generally the areas containing the abundant substance P immunoreactive (SP-IR) terminals were associated with NK-1 mRNA positive cells, some examples of this can be seen in the medial amygdaloid nucleus, the locus coeruleus, and the dorsal raphe nucleus. Contrary to these matched areas, we could not detect NK-1 mRNA positive cells in the substantia nigra, where there is a strong projection from the caudate putamen containing the substance P. Similarly the substantia gelatinosa in the trigeminal tract nucleus and the dorsal horn of the spinal cord where numerous SP-IR fibers are located, did not show abundant NK-1 mRNA positive cells. Only a few weakly labeled positive cells could be found.

Animals↗
PubMed1993

Region-specific expression of subunits of ionotropic glutamate receptors (AMPA-type, KA-type and NMDA receptors) in the rat spinal cord with special reference to nociception.

The present study attempted to explore the gene expression of the subunits (GluR1-4) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type receptor, subunit (GluR5) of kainic acid (KA)-type receptor, NR1 [a subunit of N-methyl-D-aspartate (NMDA) receptors] and the possible glutamate-binding subunit of an NMDA receptor complex in the dorsal horn of the rat spinal cords using in situ hybridization histochemistry. These results were compared with those of the spinal motor neurons. Expression of the subunits of the AMPA-type receptor was also examined at the protein level using immunocytochemistry, with reference to the motor neurons. Although all the four subunits of the AMPA-type receptor were expressed throughout the dorsal horn, the pattern of expression was different according to the dorsal horn region and to the subunits. GluR2 showed the strongest expression in the dorsal horn. Huge numbers of strongly labelled cells formed a dense collection in lamina II and superficial parts of lamina III. Many neurons in lamina II and superficial parts of lamina III expressed GluR1 moderately. Scattered neurons moderately expressing GluR3 were also seen in these regions, while the expression of GluR4 was very low. Labelling of the dorsal horn neurons by the GluR5 probe was low, and NR1 probe and a glutamate-binding subunit of an NMDA receptor complex probe labelled them diffusely with low to moderate intensity. These findings show a close relationship between the glutamergic nociceptive primary afferent system and AMPA-type receptors in which GluR2 is especially highly expressed. The present study further showed that the expression pattern of the glutamate receptors in the spinal sensory neurons differs considerably from that of spinal motor neurons. Motor neurons very strongly express GluR3 and 4, while the expression of GluR2 and GluR1 is moderate and low, respectively. Expression of GluR5 is also low in the motor neurons. However, expression of NR1 and the glutamate-binding subunit of an NMDA receptor complex is very strong. These findings indicate that the subunit composition of the AMPA-type receptors regulating motor neurons is different from that of the AMPA-type receptors in the spinal sensory neurons, and that there are at least two kinds of glutamergic systems which regulate motor neurons: via AMPA-type receptors and via NMDA receptors.

Animals↗
PubMed1993

Localization of oxytocin receptor messenger ribonucleic acid in the rat brain.

The expression of oxytocin receptor (OT-R) mRNA in the rat central nervous system was examined by in situ hybridization histochemistry using cRNA probe. Wide distribution of cells expressing OT-R mRNA was observed not only in the hypothalamus, but also in other regions. There were high levels of OT-R mRNA in the anterior olfactory nuclei, tenia tecta, olfactory tubercle, rostral most region of the frontal cortex, piriform cortex, layers 2 and 3 of the neocortex, bed nucleus of the stria terminalis, anterior medial preoptic nucleus (AV3V region), magnocellular preoptic nucleus, supraoptic nucleus, paraventricular hypothalamic nucleus, retrochiasmatic nucleus, ventromedial hypothalamic nucleus, paraventricular thalamic nucleus, central amygdaloid nucleus, medial amygdaloid nucleus, posterior cortical amygdaloid nucleus, amygdalohippocampal area, subiculum, prepositus hypoglossal nucleus, and dorsal motor nucleus of vagus. In most regions of the brain, our findings concurred with those obtained by receptor binding autoradiography using a ligand specific to OT. However, in the inferior olive nucleus, OT-R mRNA was not detected despite an abundance of binding sites showed by receptor binding autography. Despite this discrepancy OT appears to have central nervous system functions in addition to its hormonal functions.

Animals↗
PubMed1993

[Effects of exercise on immune functions in mice].

This study was carried out to examine the effects of forced running exercise on the immune functions of male ICR mice. Mice aged 4 weeks were divided into two groups: a non-exercise group (control) and a group given forced running exercise (exercise group). The exercise applied was forced running at 15m/min on a flat floor without any slope for 60 min a day. The duration of exercise was 5 days per week for 12 weeks. The results obtained were as follows: 1) After 12 weeks of forced running exercise, the weight of the anterior tibialis muscle and succinate dehydrogenase activity in the anterior tibialis muscle increased significantly (p < 0.01) in the exercise group compared with the control group. A tendency for thymus weight to increase was shown in the exercise group, and liver and spleen weights were significantly (p < 0.01) greater than in the control group. 2) The potentiation of phagocytic function of the reticulo-endothelial system, examined by the carbon clearance method, was seen in the exercise group. 3) The ability of peritoneal macrophages (M phi) to phagocytose latex beads significantly increased (p < 0.01) in the exercise group. The acid phosphatase activity of peritoneal M phi remained in both groups. However, lactate dehydrogenase activity of peritoneal M phi significantly increased (p < 0.01) in the exercise group compared with the control group. 4) The proliferation of splenocytes induced by Con A in the exercise group significantly increased (p < 0.01) compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗