Biomedical subjects

J Maeda

Publications and source records attributed to J Maeda.

At least 19 recordsLinked to original sources

PubMed2004

Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats: implications for precipitation of depression during smoking cessation.

Epidemiologic studies show that smokers with a past history of depression are more likely to relapse into depression after smoking cessation than those without a history of depression. These studies suggest the existence of a direct biological link between nicotine withdrawal and depression. To investigate the neuronal and hormonal mechanisms of the precipitation of depression during smoking cessation, we used an animal model of nicotine withdrawal and studied the function of the hypothalamic-pituitary-adrenal (HPA) axis, the abnormality of which is implicated in the pathogenesis of depression. Rats were implanted with a minipump delivering nicotine at 6.0 mg/kg/day for 12 days. The minipumps were removed in order to abruptly terminate nicotine infusion. The activity of the HPA axis was determined on day 2 of withdrawal using the stress-induced corticosterone response and the dexamethasone suppression test (DST). At the same time the expressions of glucocorticoid receptor (GR) mRNA in the hippocampus and paraventricular nucleus of hypothalamus (PVN) and corticotropin-releasing hormone (CRH) mRNA in PVN were determined by non-radioactive in situ hybridization. Nicotine withdrawal resulted in lower corticosterone levels during restraint stress, suggesting subsensitivity of the HPA axis to stress. The result of DST, however, did not show a significant difference between nicotine-withdrawal and control rats. These effects of nicotine withdrawal were not accompanied by any changes in the expressions of GR and CRH mRNA in either hippocampus or PVN. These results suggest that subsensitivity of the HPA axis to stress during nicotine withdrawal may be implicated in the precipitation of depression during smoking cessation, although GR and CRH in the HPA axis do not appear to play a significant role.

Adaptation, Physiological↗

PubMed2002

Bronchomalacia associated with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries, and chromosome 22q11.2 deletion.

Respiratory distress is one of the major complications in young infants with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD-MAPCA); however, its aetiology remains obscure. We have previously reported an association of bronchomalacia with PA-VSD-MAPCA in patients with a hemizygous deletion of chromosome 22q11.2 (del.22q11). To clarify the clinical relevance of bronchomalacia in patients with PA-VSD-MAPCA and del.22q11, we reviewed the clinical and laboratory records of four patients with PA-VSD-MAPCA who had del.22q11 and bronchomalacia. External bronchial compression by anomalous patterning of the aorta and MAPCA was documented in three of the four patients, using combinatorial examination of angiocardiography, bronchography, fibreoptic bronchoscopy and magnetic resonance imaging. One of the four patients died suddenly of severe respiratory distress at 4 years of age, while the remaining three were inoperable for complete surgical repair. Our study indicates that bronchomalacia as a result of external vascular compression may be an aetiology of early-onset respiratory distress in some patients with PA-VSD-MAPCA and del.22q11, and can significantly affect the clinical outcome.

Airway Obstruction↗

PubMed2001

Palladium-catalyzed sulfinylzincation: 1-alkynyl sulfoxides as a sulfinyl anion equivalent.

[reaction--see text] Novel Pd-catalyzed sulfinylzincation of activated alkynes was developed, wherein 1-alkynyl sulfoxides work as a sulfinylating agent. Transfer of the sulfinyl group proceeded in a highly syn-selective fashion, giving a beta-sulfinyl vinylzinc species. Using 3,3-dimethyl-1-butynyl p-tolyl sulfoxide as a sulfinyl source, heterocoupling with propiolate derivatives was also accomplished.

Journal Article↗

PubMed2001

Membrane topology of coronavirus E protein.

Coronavirus small envelope protein E has two known biological functions: it plays a pivotal role in virus envelope formation, and the murine coronavirus E protein induces apoptosis in E protein-expressing cultured cells. The E protein is an integral membrane protein. Its C-terminal region extends cytoplasmically in the infected cell and in the virion toward the interior. The N-terminal two-thirds of the E protein is hydrophobic and lies buried within the membrane, but its orientation in the lipid membrane is not known. Immunofluorescent analyses of cells expressing biologically active murine coronavirus E protein with a hydrophilic short epitope tag at the N-terminus showed that the epitope tag was exposed cytoplasmically. Immunoprecipitation analyses of the purified microsomal membrane vesicles that contain the same tagged E protein revealed the N-terminal epitope tag outside the microsomal membrane vesicles. These analyses demonstrated that the epitope tag at the N-terminus of the E protein was exposed cytoplasmically. Our data were consistent with an E protein topology model, in which the N-terminal two-thirds of the transmembrane domain spans the lipid bilayer twice, exposing the C-terminal region to the cytoplasm or virion interior.

Animals↗

PubMed2001

In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous serotonin.

[Carbonyl-(11)C]WAY-100635 has been reported to be a useful ligand for the investigation of 5-HT(1A) receptor imaging in vivo. However, the cellular distribution and the influence of endogenous serotonin (5-HT) on in vivo binding have not been fully examined. In this study, we investigated the effect of 5,7-dihydroxytryptamine-produced destruction of 5-HT neurons, reserpine-induced 5-HT depletion, and fenfluramine-induced 5-HT increase on [carbonyl-(11)C]WAY-100635 binding in vivo. There was no significant change in the uptake of [carbonyl-(11)C]WAY-100635 in the slice of 5-HT denervated rat brain except in the raphe nucleus, where 5-HT cell bodies exist. There was no obvious effect of enhanced 5-HT release by fenfluramine or decreased release by reserpine on [carbonyl-(11)C]WAY-100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl-(11)C]WAY-100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl-(11)C]WAY-100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5-HT(1A) receptor binding, and that this binding is not sensitive to endogenous 5-HT.

5,7-Dihydroxytryptamine↗

PubMed2001

Effect of endogenous dopamine on extrastriatal [¹¹C]FLB 457 binding measured by PET.

Central dopaminergic systems are known to be implicated in the pathophysiology of schizophrenia and recent in vivo dopamine receptor imaging studies have focused on the measurement of extrastriatal dopamine receptor. However, there are only a limited number of ligands that can measure the low-density D2 receptor in extrastriatal regions and their sensitivity to endogenous dopamine in extrastriatal regions has not yet been fully examined. In this study, the effect of endogenous dopamine on the extrastriatal binding of [11C]FLB 457 was examined in the rhesus monkey after facilitation with 1 mg/kg of methamphetamine (MAP) and was compared with the effect on the striatal binding of [11C]raclopride. The indices of receptor binding were obtained by four methods using cerebellum as a reference region. The bindings of [11C]FLB 457 in the frontal cortex, temporal cortex, and thalamus were not significantly changed after MAP treatment, while the striatal binding of [11C]raclopride was decreased by more than 20%. These results suggest that [11C]FLB 457 is not sensitive to endogenous dopamine in the extrastriatal regions of rhesus monkeys, despite a sufficient dose of MAP to decrease the binding of [11C]raclopride in the striatum.

Animals↗

PubMed2001

Functional brain mapping of monkey tool use.

When using a tool, we can perceive a psychological association between the tool and the body parts-the tool is incorporated into our "body-image." During tool use, visual response properties of bimodal (tactile and visual) neurons in the intraparietal area of the monkey's cerebral cortex were modified to include the hand-held tool. Visual properties of the monkey intraparietal neurons may represent the body-image in the brain. We explored tool use-induced activation within the intraparietal area and elsewhere in alert monkey brain using positron emission tomography (PET). Tool use-related activities compared with the control condition (simple-stick manipulation) revealed a significant increase in cerebral blood flow in the corresponding intraparietal region, basal ganglia, presupplementary motor area, premotor cortex, and cerebellum. These tool use-specific areas may participate in maintaining and updating the body-image for the precise guidance of a hand-held rake onto a distant reward.

Animals↗

PubMed2001

A prodrug of NMDA/glycine site antagonist, L-703,717, with improved BBB permeability: 4-acetoxy derivative and its positron-emitter labeled analog.

4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.

Animals↗

PubMed2001

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

Anti-Bacterial Agents↗

PubMed2000

Frequent association of 22q11.2 deletion with tetralogy of Fallot.

Chromosome 22q11.2 deletion causes DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome with tetralogy of Fallot (TOF), and sporadic or familial TOF. To determine the prevalence and clinical importance of the 22q11.2 deletion in TOF, a series of 212 Japanese TOF patients was studied. The type of pulmonary blood supply, which may lead to various clinical outcomes, and other additional anomalies were evaluated clinically. The 22q11.2 deletion was diagnosed by fluorescence in situ hybridization with N25 and TUPLE1 probes. Of the 212 patients examined, 28 (13%) had a 22q11.2 deletion, the frequency being higher than that in TOF patients with trisomy 21. The prevalence of the deletion in TOF patients with pulmonary atresia (PA) plus major aortico-pulmonary collateral arteries (MAPCA) was significantly higher than the value in patients with PA plus patent ductus arteriosus (PDA) (P = 0.04) or with pulmonary stenosis (PS) (P < 0.0001). All 28 patients with 22q11.2 deletion had one or more extracardiac abnormalities. Four of 9 patients with the 22q11.2 deletion and TOF-PA-MAPCA suffered from bronchomalacia, while none of 19 patients with TOF-PA-PDA or TOF-PS manifested bronchomalacia (P = 0.006). These results indicate that 22q11.2 deletion is the most frequent cause of syndromic TOF, especially for TOF-PA-MAPCA, and bronchomalacia is the clinically most important associated anomaly in TOF-PA-MAPCA patients.

Adolescent↗

PubMed2000

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding.

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [(11)C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [(11)C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors.

Animals↗

PubMed2000

Ventricular septal defect associated with microdeletions of chromosome 22q11.2.

Microdeletions of chromosome 22q11.2 (del.22q11) cause DiGeorge syndrome, velo-cardio-facial syndrome, and conotruncal anomaly face syndrome, which are commonly associated with conotruncal heart anomalies. Approximately 15% of the patients manifest ventricular septal defect (VSD), and the conal septal type of VSD has been proposed to be associated with del.22q11, since it is categorized as a conotruncal anomaly. However, the types of VSD associated with del.22q11 remain poorly studied. The purpose of this study is to assess whether conal septal VSD or other types of VSDs are associated with del.22q11. We analyzed the chromosomes of 22 consecutive patients with conal-septal VSD, prospectively, and evaluated the types of VSD observed in 3 patients with del.22q11, retrospectively. Del.22q11 was not detected in any of the 22 patients with conal septal VSD. All the VSDs observed in the 3 patients with del.22q11 were a perimembranous type of VSD, which is not a conotruncal anomaly. Our results suggest that perimembranous VSD can be associated with del.22q11, but del.22q11 is not a common cause of conal-septal VSD.

Adolescent↗

PubMed2000

Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells.

Coronavirus contains three envelope proteins, M, E and S, and a nucleocapsid, which consists of genomic RNA and N protein, within the viral envelope. We studied the macromolecular interactions involved in coronavirus assembly in cells infected with a murine coronavirus, mouse hepatitis virus (MHV). Coimmunoprecipitation analyses demonstrated an interaction between N protein and M protein in infected cells. Pulse-labeling experiments showed that newly synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi compartment, which is part of the MHV budding site. Coimmunoprecipitation analyses further revealed that M protein interacted with only genomic-length MHV mRNA, mRNA 1, while N protein interacted with all MHV mRNAs. These data indicated that M protein interacted with the nucleocapsid, consisting of N protein and mRNA 1, in infected cells. The M protein-nucleocapsid interaction occurred in the absence of S and E proteins. Intracellular M protein-N protein interaction was maintained after removal of viral RNAs by RNase treatment. However, the M protein-N protein interaction did not occur in cells coexpressing M protein and N protein alone. These data indicated that while the M protein-N protein interaction, which is independent of viral RNA, occurred in the M protein-nucleocapsid complex, some MHV function(s) was necessary for the initiation of M protein-nucleocapsid interaction. The M protein-nucleocapsid interaction, which occurred near or at the MHV budding site, most probably represented the process of specific packaging of the MHV genome into MHV particles.

Animals↗

PubMed1999

Release of coronavirus E protein in membrane vesicles from virus-infected cells and E protein-expressing cells.

Coronavirus E protein is a small viral envelope protein that plays an essential role in coronavirus assembly; coexpression of coronavirus M and E proteins results in the production of virus-like particles. The present study demonstrated that mouse hepatitis virus (MHV) E protein was released as an integral membrane protein in lipid vesicles from E-protein-expressing mammalian cells, in the absence of other MHV proteins. Furthermore, our data indicated that the E-protein-containing vesicles, which had a slightly lighter buoyant density than that of MHV, were released from MHV-infected cells. These data implied that E protein alone can drive the production and release of coronavirus envelope in the absence of M protein.

Animals↗

PubMed1999

Mecamylamine-precipitated nicotine-withdrawal aversion in Lewis and Fischer 344 inbred rat strains.

Many studies have indicated that Lewis and Fischer 344 inbred rat strains show marked differences in behavioral responses to abused drugs. In the present study, we sought to determine whether these two strains of rats show different responses in mecamylamine-precipitated nicotine-withdrawal aversion using the conditioned place preference paradigm. Rats were treated subcutaneously with 10 mg/kg/day nicotine for 7 days using an osmotic minipump. After chronic nicotine infusion, the nicotinic receptor antagonist mecamylamine produced a significant place aversion in Lewis, but not in Fischer 344 rats. These results suggest that mecamylamine-precipitated nicotine-withdrawal aversion is strongly regulated by genetic factors.

Animals↗

PubMed1999

White coat hypertension in two adolescents.

We describe two adolescent boys with white coat hypertension. Both patients had significantly high blood pressure documented on more than three occasions at clinic. No cause for hypertension or target organ damage was demonstrated. Twenty-four-hour mean ambulatory blood pressure values were normal for height and sex, which led to the diagnosis.

Adolescent↗

PubMed1999

Nursing students' response to a case study in ethics.

This paper describes the responses of undergraduate nursing students to an ethical clinical case study. Students in a baccalaureate program were given a case study before a lecture on ethical principles and the same case study after this lecture. These responses raise questions about the content of nursing ethics classes in Japan. The place of individual patient rights and the role of the family in a situation of non-disclosure about diagnosis and prognosis were major issues for the students. The responses reveal the problem of the 'nurse-in-the-middle' between the patient and others whose values differ. Students' post-lecture responses emphasized communication among the people involved.

Adult↗

PubMed1998

Phenotypic discordance in monozygotic twins with 22q11.2 deletion.

We report on male monozygotic twins with 22q11.2 deletion and discordant phenotypes. The twins had twin-to-twin transfusion syndrome. Twin 1, the smaller of the pair, had Tetralogy of Fallot, a characteristic facial appearance, swallowing dysfunction, anal atresia, short stature, and mental retardation, whereas twin 2 had a characteristic facial appearance but no other signs of the 22q11 deletion syndrome. Fluorescence in situ hybridization analysis showed a microdeletion on chromosome 22q11.2 in both twins. Zygosity analysis gave a probability of monozygosity greater than 99.999%. These observations indicate that environmental factors or postzygotic events play a role in the phenotypic variability in the twins.

Abnormalities, Multiple↗