Biomedical subjects

N Kawashima

Publications and source records attributed to N Kawashima.

At least 37 records · Page 2Linked to original sources

PubMed2000

[Chlamydia pneumoniae antibody titers in patients with acute ischemic stroke].

To evaluate an association of ischemic stroke and Chlamydia pneumoniae (C. pneumoniae) infection, we investigated specific antibodies to C. pneumoniae by ELISA in sera of 91 patients (male 53, female 38, mean age 73 years) with acute ischemic stroke. We divided the patients under clinical diagnosis into three groups, those with cardiac embolism (E group, n = 35), atherothrombotic infarction (A group, n = 29) and lacunar infarction (L group, n = 27). Carotid ultrasound examination was performed in 79 patients. The active infection, including acute primary infection, reinfection and chronic active infection, was defined by IgG or IgA index being > or = 3.00, while inactive infection, including previous and chronic inactive infection, was defined by IgG index being > or = 1.10 and < 3.00, and IgA index being < 3.00. We found that 20.7% of A group, 2.9% of E group, and 7.4% of L group had indexes suggesting an active infection (A vs. E. p = 0.040, A vs. L, p = 0.254, L vs. E, p = 0.575: Fisher's exact test). The IgG indexes of A group (mean, 1.50) were higher than those of E group (mean, 1.35) and those of L group (mean, 0.93, A vs. L, p = 0.049: unpaired t-test). The patients with carotid plaque (n = 7) had higher IgG indexes (mean, 2.28) than those without carotid plaque (n = 72, mean, 1.11, p = 0.002: unpaired t-test). These data support the association of acute atherothrombotic infarction with chronic active C. pneumoniae infection.

Acute Disease↗

PubMed1999

Phenotype-dependent expression of alpha-smooth muscle actin in visceral smooth muscle cells.

Alpha-Smooth muscle actin is one of the molecular markers for a phenotype of vascular smooth muscle cells, because the actin is a major isoform expressed in vascular smooth muscle cells and its expression is upregulated during differentiation. Here, we first demonstrate that the phenotype-dependent expression of this actin in visceral smooth muscles is quite opposite to that in vascular smooth muscles. This actin isoform is not expressed in adult chicken visceral smooth muscles including gizzard, trachea, and intestine except for the inner layer of intestinal muscle layers, whereas its expression is clearly detected in these visceral smooth muscles at early stages of the embryo (10-day-old embryo) and is developmentally downregulated. In cultured gizzard smooth muscle cells maintaining a differentiated phenotype, alpha-smooth muscle actin is not detected while its expression dramatically increases during serum-induced dedifferentiation. Promoter analysis reveals that a sequence (-238 to -219) in the promoter region of this actin gene acts as a novel negative cis-element. In conclusion, the phenotype-dependent expression of alpha-smooth muscle actin would be regulated by the sum of the cooperative contributions of the negative element and well-characterized positive elements, purine-rich motif, and CArG boxes and their respective transacting factors.

Actins↗

PubMed1999

Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation.

Periapical bone destruction earlier was shown to be mediated primarily by interleukin (IL)-1alpha in a rat model. The production and action of IL-1alpha is in turn potentially modulated by a network of cytokines, which are produced by infiltrating T-helper type 1 (Th1) and type 2 (Th2) lymphocytes, and resident connective tissue cells within the lesion. This study was designed to examine the kinetics of expression of 10 cytokines in experimentally induced murine periapical lesions, including bone-resorptive [IL-1alpha, tumour necrosis factor alpha (TNFalpha), IL-6, IL-11], Th1-type [IL-2, IL-12, interferon-gamma (IFNgamma)] and Th2-type (IL-4, IL-6, IL-10, IL-13) mediators. Cytokine mRNA expression was assessed qualitatively by reverse transcription-polymerase chain reaction, and cytokine proteins quantified by enzyme-linked immunosorbent assay. IL-1alpha and TNFalpha protein and mRNA were highly expressed, beginning on day 7, and increased to day 28. IL-6 increased to day 14 and then declined, whereas the expression of IL-11 was not modulated by pulp exposure. Most of the Th1-type cytokines, including IL-2, IL-12, and IFNgamma, showed an increase in mRNA and/or protein expression in periapical lesions after pulpal exposure; the expression of Th2-type cytokines was similarly increased, but had declined at the latest time-point (day 28), suggesting possible inhibition by Th1-type mediators. Significant correlations were observed between levels of IL-1alpha and Th1-derived pro-inflammatory mediators IL-2, IL-12, TNFalpha, and IFNgamma. There was a lack of correlation between IL-1alpha and Th2-type anti-inflammatory mediators, including IL-4, -6, and -10. These results indicate that a cytokine network is activated in the periapex in response to bacterial infection, and that Th1-modulated pro-inflammatory pathways may predominate during periapical bone destruction.

Alveolar Bone Loss↗

PubMed1999

A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.

NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.

Animals↗

PubMed1999

Effects of selective dopamine D4 receptor blockers, NRA0160 and L-745,870, on A9 and A10 dopamine neurons in rats.

Extracellular single-unit activities of dopamine neurons were recorded using chloral hydrate anaesthetized rats. We examined the reversal effects of the selective dopamine D4 receptor blockers, NRA0160 (2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole) and L-745,870 (3-[[4-(4-chlorophenyl) piperazin-1-yl] methyl]-1H-pyrrolo [2,3-b] pyridine), on dopamine agonists induced inhibition of dopamine neural activity. The firing rates of the substantia nigra pars compacta (A9) and the ventral tegmental area (A10) dopamine neurons were inhibited by methamphetamine (MAP: 1 mg/kg, i.v.) and apomorphine (APO: 40 microg/kg, i.v). NRA0160 dose-dependently reversed the inhibitory effects of MAP and APO on both A9 and A10 dopamine neurons. NRA0160 was more potent in reversing the inhibitory effects of both MAP and APO on A10 than A9 dopamine neurons. L-745,870 failed to reverse the inhibition produced by MAP on A9 and A10 dopamine neurons, whereas L-745,870, at the highest dose used, significantly reversed APO-induced inhibition of A10 but not A9 dopamine neurons. These results suggest that NRA0160 has different electrophysiological profiles on dopaminergic neural activity compared to L-745,870 and may have atypical antipsychotic effects.

Animals↗

PubMed1999

Effects of NRA0045, NRA0160, and NRA0215 on regional Fos-like immunoreactivity in the rat brain.

Pharmacological characteristics of NRA compounds, novel atypical antipsychotics, were compared with those of clozapine and haloperidol, in regard to modification of Fos-like immunoreactivity (FLI) in rats. (R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl] thiazole (NRA0045) and 2-carbamoyl-4-phenyl-5-[2-[4-(4-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0215) have a high affinity for dopamine D4 receptors, serotonin2A receptors, and the alpha1 adrenoceptor. 2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole (NRA0160) has a selective and high affinity for dopamine D4 receptors. NRA0045 and clozapine (10 and 30 mg/kg, IP) produced significant increases in FLI in both the nucleus accumbens (N. Acc.) and the medial prefrontal cortex (mPFC) but not in the dorsolateral striatum (DLS). In contrast, NRA0160 and NRA0215 (10 and 30 mg/kg, IP) significantly increased FLI in the mPFC but not in the N. Acc. and the DLS. Haloperidol (0.1 and 1 mg/kg, IP) significantly produced FLI in the N. Acc., the DLS, and the mPFC. These data indicate that the antagonistic effects of dopamine D4 receptors may contribute, at least in part, to the actions of NRA0045, NRA0160, and NRA0215 in the mPFC.

Animals↗

PubMed1999

A nonsense mutation in the myophosphorylase gene in a Japanese family with McArdle's disease.

We identified a new mutation in the myophosphorylase gene in a Japanese family with McArdle's disease. This point mutation results in the replacement of a tryptophan at amino acid position 361 with a stop codon, the third nonsense mutation in this disorder. Our findings further expand the already wide spectrum of genetic lesions associated with McArdle's disease, and establish that molecular genetic heterogeneity is also present in the Japanese population.

Aged↗

PubMed1999

Manifesting heterozygotes in a Japanese family with a novel mutation in the muscle-specific phosphoglycerate mutase (PGAM-M) gene.

Muscle-specific phosphoglycerate mutase (PGAM-M) deficiency results in a metabolic myopathy (glycogenosis type X). Three mutations in the PGAM-M gene have been described thus far, two in African-American families and one in a Caucasian family. In two of them, manifesting heterozygotes were documented. We found a new PGAM-M mutation in a Japanese family with partial PGAM deficiency: a G-to-A transition at nucleotide position 209, resulting in the substitution of a highly conserved glycine at codon 97 with aspartic acid (G97D). Two heterozygous family members for the G97D mutation presented with exercise intolerance and muscle cramps. We describe the first PGAM-M mutation in the Japanese population and confirm that heterozygous individuals can be symptomatic.

Amino Acid Sequence↗

PubMed1999

Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice.

Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E-/- selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E-/- mice and P/E+/+ wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periapical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1alpha. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases were not statistically significant. Only IL-12 was higher in P/E+/+ mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction.

Animals↗

PubMed1999

[Dental treatment and oral health care on Tokashiki Island, Okinawa].

Okinawa Prefecture has been promoting dental treatment and oral health care in places where there are no dentists. The Ministry of Health and Welfare has been cooperating with eight dental colleges, including Tokyo Medical and Dental University, for promotion thereof since 1961. The 155th promotion was held on Tokashiki Island. The caries prevalence rate of the students on Tokashiki Island was relatively high compared with the average caries prevalence rate of the same age group throughout Japan, and most of the caries were thought to be due to too many soft drinks. Resin filling was the most popular treatment during this promotion. Severe periodontal disease was observed in middle-aged persons, but we could only perform initial periodontal treatment because of the limited treatment period. Complete or partial dentures were made or repaired for many elderly. The questionnaire study showed most of the denture wearers on Tokashiki Island were satisfied with their dentures, although many dentures did not fit, and the prescription was improved. The period of this promotion was too short to perform complete dental treatment and to prevent caries and periodontal disease, and primary prevention and higher dental hygiene education should be strengthened in no dentist areas like Tokashiki Island.

Adolescent↗

PubMed1999

Receptor binding, behavioral, and electrophysiological profiles of nonpeptide corticotropin-releasing factor subtype 1 receptor antagonists CRA1000 and CRA1001.

Receptor binding, behavioral, and electrophysiological profiles of 2-[N-(2-methylthio-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-flu orophe nyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1000) and 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-fluoropheny l)- 1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1001), putative novel and selective antagonists for corticotropin-releasing factor1 (CRF1) receptor were examined. Both CRA1000 and CRA1001 inhibited 125I-ovine CRF binding to membranes of rat frontal cortex with IC50 values of 20.6 and 22.3 nM, respectively. Likewise, CRA1000 and CRA1001 inhibited 125I-ovine CRF binding to membranes of rat pituitary. In contrast, both CRA1000 and CRA1001 were without affinity for the CRF2beta receptor when examined using rat heart. In mice orally administered CRA1000 and CRA1001 reversed the swim stress-induced reduction of the time spent in the light area in the light/dark exploration task. In nonstress conditions, CRA1000 and CRA1001 were without effect on the time spent in the light area in the same task in mice. Orally administered CRA1000 and CRA1001 dose dependently reversed the effects of i.c.v. infusion of CRF on time spent in the open arms in the elevated plus-maze in rats. Lesioning of olfactory bulbs induced hyperemotionality, and this effect was inhibited by either acute or chronic oral administration of CRA1000 and CRA1001 in rats. The firing rate of locus coeruleus neurons was increased by i.c.v.-infused CRF. This excitation of locus coeruleus neurons was significantly blocked by pretreatment with i.v. administration of CRA1000 and CRA1001. CRA1000 and CRA1001 had no effects on the hexobarbital-induced anesthesia in mice, the rotarod test in mice, the spontaneous locomotor activity in mice, and a passive avoidance task in rats. These observations indicate that both CRA1000 and CRA1001 are selective and competitive CRF1 receptor antagonists with potent anxiolytic- and antidepressant-like properties in various experimental animal models, perhaps through inhibition of CRF1 receptors. CRA1000 and CRA1001 may prove effective for treating subjects with depression- and/or anxiety-related disorders without the side effects seen in the related currently prescribed medications.

Animals↗

PubMed1999

[An effective case of arterial infusion therapy of low-dose CDDP and continuous 5-FU for isolated hepatic recurrence of gastric carcinoma].

We report an effective case of arterial infusion therapy of low-dose CDDP and continuous 5-FU for isolated hepatic recurrence of gastric carcinoma. An 83-year-old man was admitted for epigastric pain and vomiting due to a huge liver metastasis of gastric carcinoma in May, 1997. Nineteen months earlier, in October of 1995, he had undergone distal gastrectomy and D2 lymph node dissection with Billroth I reconstruction. His conclusive stage and pathological findings were as follows. The conclusive stage was stage II: t3, n0, P0, H0. Histological typing was tub 2. Lymph node involvement was not detected, but venous invasion was found in the surrounding regional lymph nodes. CEA had been getting elevated from November, 1996. But he had been well until March, 1997, when CT scans revealed huge hepatic recurrence. The artery-side port was placed for hepatic arterial infusion therapy for liver metastasis. Intra-arterial bolus injection of low-dose CDDP (5 mg) and continuous intra-arterial infusion of 5-FU (250 mg/day for 7 days) were started. Through 4 courses of this arterial infusion therapy, the patient improved. CT scans revealed shrinking of liver metastasis after 3 months of this therapy. The patient was followed in an outpatient clinic and continued to receive this arterial infusion therapy once every 4 weeks. New lung metastasis was detected 9 months after the start, but liver metastasis continued to be responded. The patient died from bleeding into the bile duct from the liver metastasis 16 months after the start of arterial infusion therapy, when metastatic lesions of liver continued to shrink. Arterial infusion therapy of low-dose CDDP and continuous 5-FU may be effective for isolated hepatic recurrence of gastric carcinoma.

Aged↗

PubMed1999

[Clinical problems of home mechanical ventilation management for neuromuscular disorders].

Medical management is important for home mechanical ventilation of neuromuscular disorders. We report some problems experienced with five patients and methods to improve the care. The problems were inadequate suction of sputa, sialorrhea, underestimation of patients' symptoms and signs and excessive physical and psychological burden on patients and their families. Mechanical in-exsufflator, transdermal scopolamine and the transmission of the percutaneous oxygen saturation figures from patients' home to our hospital were effective. These management is outside the health insurance system. The Ministry of Health and Welfare must look into these issues immediately. We instructed volunteers involved in medical care for patients' family to take sufficient rest. However, the repletion of public supporters for medical home care might be warranted.

Aged↗

PubMed1998

Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice.

To study the function of GLAST, a glutamate transporter highly expressed in the cerebellar Bergmann astrocytes, the mouse GLAST gene was inactivated. GLAST-deficient mice developed normally and could manage simple coordinated tasks, such as staying on a stationary or a slowly rotating rod, but failed more challenging task such as staying on a quickly rotating rod. Electrophysiological examination revealed that Purkinje cells in the mutant mice remained to be multiply innervated by climbing fibres even at the adult stage. We also found that oedema volumes in the mutant mice increased significantly after cerebellar injury. These results indicate that GLAST plays active roles both in the cerebellar climbing fibre synapse formation and in preventing excitotoxic cerebellar damage after acute brain injury.

ATP-Binding Cassette Transporters↗

PubMed1998

Application of in situ hybridization technique for quantitative assessment of ongoing symptomatic Epstein-Barr virus infection after living related liver transplantation.

For quantitative assessment of ongoing symptomatic Epstein-Barr virus (EBV) infection in pediatric recipients of liver transplantation, we determined the number of peripheral blood mononuclear cells (PBMC) infected by EBV by in situ hybridization (ISH) and related the results with clinical courses of those patients. Twenty-four patients had symptomatic EBV infection between February 1995 and March 1996. Blood samples were obtained from these 24 patients at the time of acute phase, from 13 of them during convalescence, and 37 pediatric patients before transplantation. ISH was performed on the PBMC and polymerase chain reaction (PCR) on DNA from whole blood. Oligonucleotide probes for ISH were chosen from coding sequences of EBV-encoded small nuclear RNA 1 (EBER1). Results of ISH were reported in a number of cells expressing EBER1/5 x 104 PBMC (#EBER1). Fever, diarrhea, upper respiratory symptoms, pleural effusion, ascites, lymphadenopathy, and lymphoproliferative disease (LPD) accompanied with EBV infection proven by serology, viral-specific stain or PCR were regarded as EBV related diseases (EBVD). All samples with positive #EBER1 were accompanied by positive EBV PCR. #EBERI was 68.2 +/- 144.9 (mean +/- SD) ranging from 0 to 621 in the acute phase, 0.20 +/- 0.41 ranging from 0 to 2 in the convalescence phase, 0.27 +/- 0.77 in 23 preoperative patients with positive serology, and 0 in all 14 preoperative patients with negative serology. The #EBER1 in ongoing EBVD was significantly greater than that of patients in convalescence or before transplantation. Patients with #EBERI greater than 10 had a significantly lower chance of convalescence and a higher mortality than patients with #EBER 1 less than 10. We conclude that #EBER1 could be a specific and quantitative marker of EBVD and might predict progression to LPD.

Child↗

PubMed1997

Differential expression of isoforms of PSD-95 binding protein (GKAP/SAPAP1) during rat brain development.

PSD-95/SAP90, which binds to the C-terminus of NMDA receptor and Shaker-type potassium channel, is one of the major postsynaptic density proteins. Recently, novel classes of proteins interacting with the guanylate kinase domain of PSD-95 have been identified, guanylate kinase-associated protein (GKAP) and SAP90/PSD-95-associated proteins (SAPAPs). Here we report the isolation of new isoforms of PSD-95 binding protein (GKAP/SAPAP1) using the yeast two-hybrid system. The isolated protein directly interacts with the guanylate kinase domain of PSD-95. Northern blot analyses revealed that the expression of these isoforms containing distinct N-terminal sequences is differentially regulated during brain development. The present findings suggest that each isoform of the PSD-95 binding protein is differentially expressed in a development-dependent manner and may be involved in the complex formation of PSD-95 and channel/receptors at the postsynaptic density.

Amino Acid Sequence↗

PubMed1997

Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.

ATP-Binding Cassette Transporters↗

PubMed1997

Defense responses of dentin/pulp complex to experimentally induced caries in rat molars: an immunohistochemical study on kinetics of pulpal Ia antigen-expressing cells and macrophages.

Experimental caries was induced in rats that were inoculated orally with Streptococcus mutants and maintained on a cariogenic diet. During the caries process, kinetics of the pulpal la antigen-expressing cells and macrophages was monitored immunohistochemically and was correlated with caries depth and the status of reparative dentin formation. Initial pulpal response was characterized by a localized accumulation of la antigen-expressing cells beneath the dentinal tubules communicating with the superficial caries. This was followed by a caries-depth related increase of la antigen-expressing cells and macrophages in the coronal pulp. The accumulation of these cells under the dentin was most apparent when the caries had progressed into the reparative dentin. These findings suggest that the response of la antigen-expressing cells to carious irritants triggers the defense reactions of the pulp. The intensity of the defense reactions may be correlated with the permeability of carious dentin.

Animals↗