Biomedical subjects

S Kawahara

Publications and source records attributed to S Kawahara.

At least 19 recordsLinked to original sources

PubMed2005

N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit delta2 mutant mice.

Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently consistent with this, glutamate receptor subunit delta2 null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay paradigm. However, these mutant mice successfully learn in trace paradigm, even in '0-trace paradigm,' in which the unconditioned stimulus starts just after the conditioned stimulus terminates. Our previous studies revealed that the hippocampus and the muscarinic acetylcholine receptors play crucial roles in 0-trace paradigm in glutamate receptor subunit delta2 null mutant mice unlike in wild-type mice, suggesting a large contribution of the forebrain to 0-trace conditioning in this type of mutant mice. In the present study, we investigated the role of N-methyl-D-aspartate receptors in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice. Mice were injected intraperitoneally with the noncompetitive N-methyl-d-aspartate receptor antagonist (+)MK-801 (0.1mg/kg) or saline, and conditioned with 350-ms tone conditioned stimulus followed by 100-ms periorbital shock unconditioned stimulus. Glutamate receptor subunit delta2 null mutant mice that received (+)MK-801 injection exhibited a severe impairment in acquisition of the conditioned response, compared with the saline-injected glutamate receptor subunit delta2 null mutant mice. In contrast, wild-type mice were not impaired in acquisition of 0-trace conditioned response by (+)MK-801 injection. After the injection solution was changed from (+)MK-801 to saline, glutamate receptor subunit delta2 null mutant mice showed a rapid and partial recovery of performance of the conditioned response. On the other hand, when the injection solution was changed from saline to (+)MK-801, glutamate receptor subunit delta2 null mutant mice showed a marked impairment in expression of the pre-acquired conditioned response, whereas impairment of the expression was small in wild-type mice. Injection of (+)MK-801 had no significant effects on spontaneous eyeblink frequency or startle eyeblink frequency to the tone conditioned stimulus in either glutamate receptor subunit delta2 null mutant mice or wild-type mice. These results suggest that N-methyl-D-aspartate receptors play critical roles both in acquisition and expression of the conditioned response in 0-trace eyeblink conditioning in glutamate receptor subunit delta2 null mutant mice.

Animals↗

PubMed2003

Trans-Tenon's retrobulbar triamcinolone infusion for the treatment of uveitis.

AIM: To assess efficacy and complications of trans-Tenon's retrobulbar infusion of triamcinolone acetonide for posterior uveitic inflammation. METHODS: Non-randomised, uncontrolled, retrospective study of 51 eyes of 37 patients who underwent triamcinolone infusion for vitritis, cystoid macular oedema (CMO), or posterior retinal vasculitis using a long blunt cannula via an incision made through conjunctiva and Tenon's capsule. RESULTS: Overall clinical efficacy was 86%; 96% for vitritis, 82% for CMO, and 33% for posterior retinal vasculitis. Mean visual acuity improved within 1 month after triamcinolone infusion (p <0.05). Cataract progression and intraocular pressure elevation were observed in 31% and 27% of eyes, respectively. CONCLUSION: Trans-Tenon's retrobulbar triamcinolone infusion may be a safe and effective treatment for posterior uveitic inflammation.

Adult↗

PubMed2001

Age-dependent impairment of delay and trace eyeblink conditioning in mice.

The age effect on classical eyeblink conditioning in unrestrained mice (C57BL/6J strain) was evaluated. Mice were trained at one of three age periods (8, 45-50 or 85-90 weeks). In the delay paradigm, significant learning deficits were evident in the 85-90 week-old group, but no deficits were observed in the behavior of the 45-50 week-old group. On the other hand, in the trace paradigm with a stimulus-free trace interval of 500 ms, significant deficits became apparent at the age of 45-50 weeks. These results indicate that trace eyeblink conditioning is more susceptible to age-related deterioration of memory in mice than delay eyeblink conditioning.

Aging↗

PubMed2001

Impaired delay but normal trace eyeblink conditioning in PLCbeta4 mutant mice.

To elucidate the functional role of phospholipase Cbeta4 (PLCbeta4), which is highly expressed in the Purkinje cells of the rostral cerebellum, cerebellar long-term depression (LTD) and delay and trace eyeblink conditioning were investigated in PLCbeta4-deficient mice. Rostral cerebellar LTD and delay eyeblink conditioning were severely impaired, whereas trace eyeblink conditioning was not. These results indicate that PLCbeta4 is essential for LTD in the rostral cerebellum and delay conditioning, but not trace conditioning. Rostral cerebellar LTD may be required as a neural substrate for delay conditioning, but is not required for trace conditioning.

Afferent Pathways↗

PubMed2001

Phospholipase Cbeta4 and protein kinase Calpha and/or protein kinase CbetaI are involved in the induction of long term depression in cerebellar Purkinje cells.

Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKCgamma-deficient mice, thus, in the present study, we examined cerebellar LTD in PLCbeta4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLCbeta1 was expressed weakly and uniformly, PLCbeta2 was not detected, PLCbeta3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLCbeta4 was expressed uniformly throughout. In PLCbeta4-deficient mice, expression of total PLCbeta, the mGluR1-mediated Ca(2+) response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKCalpha, -betaI, -betaII, and -gamma in mouse cerebellar Purkinje cells during LTD induction. Both PKCalpha and PKCbetaI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLCbeta4 in rostral cerebellar Purkinje cells induced LTD via PKCalpha and/or PKCbetaI.

Animals↗

PubMed2001

Modulation of oscillatory neural activities by cholinergic activation of interneurons in the olfactory center of a terrestrial slug.

The neurons in the procerebrum (PC) of the terrestrial slug Limax marginatus show regular oscillation of their membrane potential, and the oscillation has been implicated in olfactory processing. The neural mechanisms for the generation and modulation of the oscillation have been poorly understood. In the present work, we examined the ionic conductances evoked by acetylcholine (ACh) in the PC neurons and the effects of ACh application on the population activities of intrinsic and extrinsic neurons. The PC neurons are categorized into bursting neurons, which are putative local inhibitory neurons, and nonbursting neurons, which likely mediate the input and output of information in the PC. Bath application of ACh augmented the local field potential oscillation in the PC. Perforated patch recording from single PC neurons revealed that ACh has direct excitatory effects on bursting neurons, while it suppresses the activity of nonbursting neurons, possibly via augmented inhibitory synaptic input from bursting neurons. The correlation between the membrane potential of bursting neurons and the frequency of oscillation suggests that bursting neurons are the main determinant of the oscillation frequency. Application of ACh also resulted in a reduction of the oscillation amplitude in the olfactory nerve, suggesting that the frequency modulation in the oscillatory network could change the activities in the follower neurons.

Acetylcholine↗

PubMed2001

Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice.

N-methyl-D-aspartate (NMDA) receptors are involved in synaptic plasticity and play a critical role in learning and memory. We investigated the effects of the noncompetitive NMDA receptor antagonist (+)MK-801 on classical eyeblink conditioning of mice, using various interstimulus intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). A tone was used for the CS and a periorbital shock was used for the US. In the delay paradigm, in which the US coterminated with the CS or started immediately after CS offset, the effect of (+)MK-801 (0.1mg/kg, i.p.) was a slight impairment in the acquisition of the conditioned response (CR). During subsequent CS-alone trials, the responses of (+)MK-801-injected mice were extinguished as easily as those of saline-injected mice. In the trace paradigm, (+)MK-801 impaired acquisition of the CR with a trace interval of 250 ms more than it did with a trace interval of 100 ms, and more than in the delay paradigm. (+)MK-801 injected after acquisition of 250-ms trace conditioning did not impair expression or extinction of the CR. These results suggest that NMDA receptors are involved in acquisition of the CR during longer trace interval conditioning more than during shorter trace interval conditioning or delay conditioning, and that their contribution to extinction is much smaller than their contribution to acquisition in mouse eyeblink conditioning.

Animals↗

PubMed2001

Long-trace interval eyeblink conditioning is impaired in mutant mice lacking the NMDA receptor subunit epsilon 1.

To elucidate the role of the N-methyl-D-aspartate (NMDA) -type glutamate receptor subunit epsilon 1 (GluR epsilon 1) in classical eyeblink conditioning, delay and trace eyeblink conditioning were investigated in GluR epsilon 1-null mutant mice. In delay conditioning and short-trace interval conditioning with a trace interval of 250 ms, GluR epsilon 1 mutant mice attained a normal level of the conditioned response (CR), although acquisition was a little slower than in wild-type mice. In contrast, GluR epsilon 1 mutant mice exhibited severe impairment of the attained level of the CR and disturbed temporal pattern of CR expression in trace conditioning with a longer trace interval of 500 ms. These findings indicate that GluR epsilon 1 is essential for long-trace interval eyeblink conditioning. The impairments of the associative learning with a long temporal separation between the conditioned and unconditioned stimuli observed in the GluR epsilon 1 mutant mice could be attributed to an impairment of hippocampal long-term potentiation in this line of mutant mice.

Animals↗

PubMed2001

Classical eyeblink conditioning in glutamate receptor subunit delta 2 mutant mice is impaired in the delay paradigm but not in the trace paradigm.

In mice lacking glutamate receptor subunit delta 2 (GluR delta 2(-/-_ mice), cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell synapses is disrupted. Unlike the cerebellar LTD-deficient mice previously used for eyeblink conditioning, however, the abnormalities of the GluR delta 2(-/-) mice are restricted to the cerebellar cortex. In delay eyeblink conditionings (interstimulus interval of 252 and 852 ms), in which the conditioned stimulus (CS) overlaps temporally with a coterminating unconditioned stimulus (US), GluR delta 2(-/-) mice are severely impaired in learning, strongly supporting the hypothesis that cerebellar cortical LTD is essential for delay conditioning. In the trace paradigm, in which a stimulus-free trace interval of 500 ms intervened between the CS and US, GluR delta 2(-/-) mice learned as successfully as wild-type mice, indicating that cerebellar LTD is not necessary for trace conditioning. Thus, the present study has revealed a cerebellar LTD-independent learning in eyeblink conditioning.

Animals↗

PubMed2001

Impairment of eyeblink conditioning in GluRdelta2-mutant mice depends on the temporal overlap between conditioned and unconditioned stimuli.

Mice lacking the glutamate receptor subunit delta2 (GluRdelta2) are deficient in cerebellar long-term depression (LTD) at the parallel fibre-Purkinje cell synapses. We conducted delay and trace eyeblink conditioning with these mice, using various temporal intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). During trace conditioning in which a stimulus-free trace interval (TI) of 250, 100 or 50 ms intervened between the 352-ms tone CS and 100-ms US, GluRdelta2-mutant mice learned as successfully as wild-type mice. Even in the paradigm with TI = 0 ms, in which the end of CS and onset of US are simultaneous, there was no difference between the GluRdelta2-mutant and wild-type mice in their acquisition of a conditioned response. However, in the delay paradigm in which the 452-ms CS overlapped temporally with the coterminating 100-ms US, GluRdelta2-mutant mice exhibited severe learning impairment. The present study together with our previous work [Kishimoto, Y., Kawahara, S., Suzuki, M., Mori, H., Mishina, M. & Kirino, Y. (2001) Eur. J. Neurosci., 13, 1249-1254], indicates that cerebellar LTD-independent learning is possible in paradigms without temporal overlap between the CS and US. On the other hand, GluRdelta2 and cerebellar LTD are essential for learning when there is CS-US temporal overlap, suggesting that the cerebellar neural substrates underlying eyeblink conditioning may change, depending on the temporal overlap of the CS and US.

Animals↗

PubMed2001

Identification and expression of a novel gene in odour-taste associative learning in the terrestrial slug.

Odour-taste associative learning in the terrestrial slug offers a useful model for long-term memory formation and retention. The genes which are expressed over 2 h after a learning event are thought to include those related to memory formation and/or consolidation. It is very important to examine what kinds of genes are expressed following associative learning. We identified a novel slug gene, the expression of which was regulated by associative learning and mostly restricted to the procerebrum (PC), a place that olfactory information is believed to be processed in slug. This gene encodes a 121 amino acid, 18 kDa secretory protein which we term LAPS18. Expression of the LAPS18 gene was induced in somata and the protein spread to neurites in the PC of slugs subjected to paired conditioning. Recombinant LAPS18 promoted the aggregation and movement of PC neurones in culture and they were blocked by the anti-LAPS18 antibody. Beads coupled with LAPS18 protein attached to PC neurones and the beads aggregated through PC cells but not by themselves, suggesting that LAPS18 may require a counterpart molecule for PC neurone aggregation. An increased expression and translocation of LAPS18 protein after paired conditioning may be needed for long-term memory formation and retention in the slug. Since genes homologous to LAPS18 genes in the land slug Limax are found from vertebrates including human, analysing the expression and function of LAPS18 may be important in understanding the molecular mechanism of memory formation and retention.

Amino Acid Sequence↗

PubMed2001

Ab initio molecular orbital evaluation of the hydrogen bond energy of base pairs formed between substituted 1-methylcytosine derivatives and 9-methylguanine.

The substitution effect on hydrogen bond energy of the Watson-Crick type base pair between 9-methylguanine (G) and chemically modified 1-methylcytosine (CX) derivatives was evaluated by ab initio molecular orbital theory. A remarkable trend was observed in the substitution effect of the hydrogen bond stability: Cytosine derivatives possessing an electron-donating group form stable base pairs with guanine. However, both the hydrogen bond distance and the charge distribution were not good indexes for the hydrogen bond status in CX-G base pairing.

Base Pairing↗

PubMed2001

[In vitro antimycobacterial activities of a new quinolone, balofloxacin].

Balofloxacin (BLFX), a newly developed fluoroquinolone, was studied for its in vitro antimycobacterial activity by the agar dilution method with 7H11 agar medium. The MIC90s were as follows: 0.39 microgram/ml for M. tuberculosis, > 50 micrograms/ml for M. avium, > 50 micrograms/ml for M. intracellulare, 0.39 microgram/ml for M. kansasii, 0.39 microgram/ml for M. fortuitum, > 50 micrograms/ml for M. abscessus, and 50 micrograms/ml for M. chelonae. The antimycobacterial activity of BLFX was comparable or slightly inferior to that of levofloxacin (LVFX). Considering the present findings and pharmacokinetics of BFLX, it appears that BFLX may achieve favorable outcome in the treatment of patients with infection due to M. tuberculosis, M. kansasii, or M. fortuitum similar to that of ofloxacin or LVFX.

Anti-Infective Agents↗

PubMed2001

[Comparison of in vitro antimicrobial activities of ofloxacin, levofloxacin, ciprofloxacin, and sparfloxacin against various mycobacteria].

In vitro antimicrobial activities of ofloxacin (OFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), and sparfloxacin (SPFX) were compared against various mycobacteria using the agar dilution method with 7H11 medium, and the following results were obtained. (1) These four new quinolones showed excellent antimicrobial activities against M. tuberculosis, M. kansasii, and M. fortuitum. (2) SPFX was most active against slowly growing mycobacteria. The activity against M. tuberculosis was in the order of SPFX > CPFX > LVFX > OFLX. The activity against M. kansasii was in the order of SPFX > LVFX > OFLX > or = CPFX. (3) On the other hand, CPFX was most active against rapidly growing mycobacteria. The activity against M. fortuitum was in the order of CPFX > SPFX > LVFX > OFLX. Considering the in vitro antimicrobial activities and the pharmacokinetics of these four drugs, they could achieve favorable clinical outcomes for all the patients with pulmonary infection due to M. tuberculosis or M. fortuitum and some of the patients with pulmonary infection due to M. kansasii or M. chelonae.

Anti-Infective Agents↗

PubMed2001

[Clinical study on the cases in which INH or RFP was discontinued during treatment for pulmonary tuberculosis].

Short course regimens; 2HRZ (E)(S)/4HR (E), 6HRS (E)/3-6HR and 6-9HR have been accepted as a standard chemotherapy (SC) for initial treatment of pulmonary tuberculosis in Japan. We studied the frequency of the treatment completion, the causes of the treatment failure and the outcome of the patients in whom INH or RFP was discontinued within 6 months after starting SC. The subjects included 597 newly diagnosed culture positive pulmonary tuberculosis patients admitted to 16 national hospital in 1996. Results were as follows. 1. In 47 (7.9%) of the 597 patients, either INH (19; 3.2%) or RFP (33; 5.5%) was discontinued. These 47 cases were defined as a SC incompleted group and the other 550 as a SC completed group. 2. The patients in the SC incompleted group were seen more frequently in the ages of 20s (11.9%), 50s (10.9%), 60s (11.7%) or 70s (11.4%). 21 (13.6%) of 154 female patients and 26 (5.9%) of 443 male patients were in the SC incompleted group. 3. The causes of cessation of INH or RFP were drug side effects (33; 5.5%), drug resistance (10; 1.7%) and complications or underlying diseases (8; 1.3%). 4. Fever or eruption (19; 3.2%) and drug induced hepatitis (12; 2.0%) were frequently seen as drug related side effects causing the cessation of INH or RFP. 5. The rate of culture negative conversion of TB bacilli at 6 months after the start of the treatment was 98.9% in the SC completed and 88.9% in the SC incompleted group respectively. In the SC incompleted group, there were three cases continuously positive and two other patients who relapsed and became culture positive again. In these five patients, INH or RFP was discontinued because of drug resistance.

Adolescent↗

PubMed2001

[Tuberculosis of the elderly (above the age of 75) in national hospitals].

In Japan tuberculosis is becoming rapidly the disease of the elderly. We studied the background, the type and level of hospital cares needed, and the outcome of patients with pulmonary tuberculosis (sputum smear and/or culture positive) above the age of 75 who were admitted to 8 national hospitals during the period from January 1 to December 31, 1997. The study included 150 patients (male: 109, female: 41, mean age: 81.6), of whom 25% needed care in a single-bed room, 84.3% had underlying diseases (cardiovascular diseases: 43.3%, malignant diseases: 20.9%, neuro-psychiatric diseases: 13.4%), and 47.6% needed cares mainly in feeding and excretions. 92 patients (62.6%) improved and 45 patients (30.6%) died, of whom the cause of death was directly related to tuberculosis in 42. The mean hospital stay was 4.7 months. However, in 42 patients whose cause of death was related to tuberculosis, 66% died within 3 months, while in 102 patients who were discharged 71% stayed more than 3 months. The same comparison was done in 508 patients with bacteriologically proven tuberculosis above the age of 75 admitted to National Tokyo Hospital during the period from 1990 to 1999. The result was almost the same, among 133 patients died in the hospital 60% died within 3 months, while in 375 patients who were discharged hospital stay was more than 3 months in 70%. In the near future, the elderly will occupy more than 25% of the beds of the tuberculosis ward in Japan and most of them have underlying diseases other than tuberculosis. Because tuberculosis, once the disease of the young, is becoming rapidly the disease of the elderly, it is imperative for us to make necessary adjustments to meet this inevitable trend.

Aged↗

PubMed2001

[Anesthesia for electroconvulsive therapy during pregnancy--a case report].

We experienced anesthetic management for ECT in a patient with psychiatric disease during the third trimester of pregnancy. The 24 year-old patient had been on oral antipsychotics prescribed to treat schizophrenia for ten years. Her signs and symptoms deteiorated during pregnancy in spite of increased doses of antipsychotics. With tocolytic agent administered intravenously, anesthesia was induced by intravenous thiamylal immediately followed by intravenous suxamethonium for muscle relaxation. Alternative current was applied on both side of the head after the sufficient anesthesia had been obtained. The patient received intermittent mandatory ventilation by breathing mask with 100% oxygen during the procedure. Along with monitoring of maternal hemodynamic variables and arterial oxygen saturation (Spo2), fetal heart rate and uterine contraction were recorded by cardiotocogram throughout the procedure. At the first two treatments, the patient showed neither significant uterine contraction nor fetal heart rate changes. At the third treatment, continuous uterine contraction refractory to tocolysis was recorded for six minutes, resulting in fetal bradycardia. At the sixth treatment, general anesthesia was induced and maintained by sevoflurane in oxygen followed by suxamethonium for muscle relaxation. The uterine contraction was remarkably diminished and fetal heart rate remained unchanged during the procedure. In conclusion, inhalation anesthesia is beneficial for ECT in the last stage of pregnancy to reduce uterine contraction by potential uterine relaxation effect of anesthetics.

Adult↗

PubMed2001

[Pulmonary involvement, pleural effusion, and electrocardiographic abnormality in hypereosinophilic syndrome].

A 47-year-old man was admitted to our hospital with complaints of cough and shortness of breath. Chest radiography showed infiltration of the right lung and left pleural effusion, the eosinophil count increased notably in the peripheral blood, sputum, and pleural effusion. Transbronchial lung biopsy revealed the invasion of eosinophils like eosinophilic pneumonia. Heart failure easily developed in this patient after the intravenous infusion. Myocardial involvement was suspected, and hypereosinophilic syndrome was diagnosed. After prednisolone was administered, the peripheral blood eosinophil count normalized rapidly, and subsequently, the pleural effusion and infiltration shadows in the lung disappeared.

Anti-Inflammatory Agents↗