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Biomedical subjects

S Namura

Publications and source records attributed to S Namura.

At least 37 records · Page 2Linked to original sources

Attenuation of focal cerebral infarct in mice lacking NMDA receptor subunit NR2C.

Neuronal death following cerebral vascular occlusion may be caused in part by the action of glutamate acting through the NMDA receptor. Here we demonstrate that gene disruption of the NR2C subunit of the NMDA receptor attenuates focal cerebral ischemic injury after permanent MCA occlusion, and that a low level of NR2C is expressed and active in the cerebral cortex. NR2C-deficient mice do not show impairment of motor coordination or motor learning. Therefore the development of drugs selectively inhibiting NR2C may prove beneficial in the treatment of stroke and traumatic brain injuries.

Animals↗

Attenuation of delayed neuronal death after mild focal ischemia in mice by inhibition of the caspase family.

Inhibitors of apoptosis and of excitotoxic cell death reduce brain damage after transient and permanent middle cerebral artery occlusion. We compared the neuroprotective effects of two caspase family inhibitors with the N-methyl-D-aspartate receptor antagonist (+)-MK-801 hydrogen maleate (MK-801) in a newly characterized cycloheximide-sensitive murine model of transient middle cerebral artery occlusion (30 minutes) in which apoptotic cell death is prominent. Ischemic infarction, undetected by 2,3,5-triphenyltetrazolium chloride staining at 24-hour reperfusion, featured prominently in the striatum at 72 hours and 7 days on hematoxylin-eosin-stained sections. Markers of apoptosis, such as oligonucleosomal DNA damage (laddering) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL)-positive cells first appeared at 24 hours and increased significantly at 72 hours and 7 days after reperfusion. The TUNEL-labeled cells were mostly neurons and stained negative for glial (GFAP, glial fibrillary acid protein) and leukocyte specific markers (CD-45). The caspase inhibitors, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD.FMK; 120 ng intracerebroventricularly) or N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone (z-DEVD.FMK; 480 ng intracerebroventricularly) decreased infarct size and neurologic deficits when administered 6 hours after reperfusion. The extent of protection was greater than in models of more prolonged ischemia or after permanent occlusion, and the therapeutic window was extended from 0 to 1 hours after 2-hour middle cerebral artery occlusion to at least 6 hours after brief ischemia. Also, z-VAD.FMK and z-DEVD.FMK treatment decreased oligonucleosomal DNA damage (DNA laddering) as assessed by quantitative autoradiography after gel electrophoresis. By contrast, MK-801 protected brain tissue only when given before ischemia (3 mg/kg intraperitoneally), but not at 3 or 6 hours after reperfusion. Despite a decrease in infarct size after MK-801 pretreatment, the amount of DNA laddering did not decrease 72 hours after reperfusion, thereby suggesting a mechanism distinct from inhibition of apoptosis. Hence, 30 minutes of reversible ischemia augments apoptotic cell death, which can be attenuated by delayed z-VAD.FMK and z-DEVD.FMK administration with preservation of neurologic function. By contrast, the therapeutic window for MK-801 does not extend beyond the time of occlusion, probably because its primary mechanism of action does not block the development of apoptotic cell death.

Amino Acid Chloromethyl Ketones↗

Prolonged therapeutic window for ischemic brain damage caused by delayed caspase activation.

Apoptotic cell death is prominent in neurodegenerative disorders, such as Alzheimer's disease and Huntington's disease, and is found in cerebral ischemia. Using a murine model of delayed cell death, we determined that cleavage of zDEVD-amino-4-trifluoromethyl coumarin (zDEVD-afc) in brain homogenate, a measure of caspase activation, increased initially 9 hours after brief (30 minutes) middle cerebral artery occlusion along with caspase-3p20 immunoreactive cleavage product as determined by immunoblotting. zDEVD-afc cleavage activity was blocked by pretreatment or posttreatment with the caspase-inhibitor N-benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethyl-ketone (zDEVD-fmk), and ischemic damage was reduced when the drug was injected up to 9 hours after reperfusion. The protection was long lasting (21 days). Hence, the period before caspase activation defined the therapeutic opportunity for this neuroprotective agent after mild ischemic brain injury. Prolonged protection after caspase inhibition plus the extended treatment window may be especially relevant to the treatment of neurodegenerative disorders.

Animals↗

Consistent injury in the striatum of C57BL/6 mice after transient bilateral common carotid artery occlusion.

OBJECTIVE: The recent availability of transgenic mice enables us to study the functional role of single gene products in cerebral ischemia. To establish an experimental murine model of transient forebrain ischemia, this study examined the temporal profile of ischemic neuronal damage in the striatum after bilateral common carotid artery occlusion. METHODS: C57BL/6 mice, which are frequently used for genetic manipulations, were subjected to 15-minute bilateral common carotid artery occlusion. Ischemic injury was examined (4, 8, 24, 48, and 96 h after reperfusion) by Nissl staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeling, and nuclear staining with Hoechst 33258 dye. RESULTS: Regional cerebral blood flow was decreased to 11 +/- 6% of control values during the ischemic insult. Striatal injury was observed in 95% of animals examined after 15-minute bilateral common carotid artery occlusion. The number of small and medium-size neurons in the striatum was significantly (P < 0.05) decreased 8 hours after reperfusion and continued to decrease until 96 hours, whereas the number of large neurons remained constant. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeling-positive cells appeared in the dorsomedial region of the striatum 48 hours after the ischemic insult and throughout the striatum 96 hours after the ischemic insult. Brain sections stained with Hoechst 33258 dye also demonstrated apoptotic nuclei 96 hours after the ischemic insult. CONCLUSION: Striatal injury after transient forebrain ischemia is reproducible in C57BL/6 mice and is a good model to study the molecular mechanisms of ischemic injury, including delayed neuronal death, using transgenic mice.

Animals↗

Ultrasonic imaging of the temporomandibular joint: a clinical trial for diagnosis of internal derangement.

Kinematic imaging of the temporomandibular joint (TMJ) was applied for diagnosis of TMJ disorders using an ultrasonic diagnostic imaging system. Patients with a normal TMJ (male, 24 y 1 mon) and a symptomatic TMJ (female, 20 y 2 mon) were selected for imaging. The transducer must be placed in a specific location in order to propagate ultrasound through soft tissue because it is difficult for ultrasound to penetrate bone such as the condyle and the eminence. Therefore the ultrasonic images were not taken in sagittal cross-section, as is the case with magnetic resonance images. The ultrasonic diagnostic imaging system showed a transverse cross-section and no hard tissue images. It was difficult to become accustomed to these images, thus making it difficult to find differences between the normal TMJ and the symptomatic TMJ on the basis of static ultrasonic images alone. However a difference between the kinematic images of the normal and symptomatic TMJ was observed during jaw opening. Irregularity in the striated pattern of the soft tissue surrounding the condyle was observed in the image of the symptomatic TMJ. In order to make a precise diagnosis using ultrasonic imaging, it may be useful to understand the kinematics of the soft tissue surrounding the TMJ during jaw opening and closing.

Adult↗

Collateral projections of single neurons in the posterior thalamic region to both the temporal cortex and the amygdala: a fluorescent retrograde double-labeling study in the rat.

It has been reported that the acoustic thalamus of the rat sends projection fibers to both the temporal cortical areas and the lateral amygdaloid nucleus to mediate conditioned emotional responses to an acoustic stimulus. In the present study, fluorescent retrograde double labeling with Fast Blue and Diamidino Yellow has been used in the rat to examine whether single neurons in the posterior thalamic region send axon collaterals to both the temporal cortical areas and lateral amygdaloid nucleus. One of the tracers was injected into the lateral amygdaloid nucleus and the other into the temporal cortical areas close to the rhinal sulcus. Neurons double-labeled with both tracers were found mainly in the posterior intralaminar nucleus and suprageniculate nucleus, and to a lesser extent in the subparafascicular nucleus and medial division of the medial geniculate nucleus. No double-labeled neurons were seen in either the dorsal or ventral division of the medial geniculate nucleus. When one of the tracers was injected into the lateral amygdaloid nucleus and the other into either the dorsal portion of the temporal cortex, the dorsal portion of the entorhinal cortex, or the posterior agranular insular cortex, no double-labeled neurons were found in the posterior thalamic region. The present results indicate that a substantial number of single neurons in the acoustic thalamus project to both the limbic cortical areas and lateral amygdaloid nucleus by way of axon collaterals. These neurons may be implicated in affective and autonomic components of responses to multi-sensory stimuli, including acoustic ones.

Amygdala↗

Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase.

Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30), an abundant nuclear protein activated by DNA nicks, mediates cell death in vitro by nicotinamide adenine dinucleotide (NAD) depletion after exposure to nitric oxide. The authors examined whether genetic deletion of PARP (PARP null mice) or its pharmacologic inhibition by 3-aminobenzamide (3-AB) attenuates tissue injury after transient cerebral ischemia. Twenty-two hours after reperfusion following 2 hours of filamentous middle cerebral artery occlusion, ischemic injury was decreased in PARP-/- and PARP+/- mice compared with PARP+/+ litter mates, and also was attenuated in 129/SV wild-type mice after 3-AB treatment compared with controls. Infarct sparing was accompanied by functional recovery in PARP-/- and 3-AB-treated mice. Increased poly(ADP-ribose) immunostaining observed in ischemic cell nuclei 5 minutes after reperfusion was reduced by 3-AB treatment. Levels of NAD--the substrate of PARP--were reduced 2 hours after reperfusion and were 35% of contralateral levels at 24 hours. The decreases were attenuated in PARP-/- mice and in 3-AB-treated animals. Poly(ADP-ribose)polymerase cleavage by caspase-3 (CPP-32) has been proposed as an important step in apoptotic cell death. Markers of apoptosis, such as oligonucleosomal DNA damage, total DNA fragmentation, and the density of terminal deoxynucleotidyl transferase dUTP nick-end-labelled (TUNEL +) cells, however, did not differ in ischemic brain tissue of PARP-/- mice or in 3-AB-treated animals versus controls, although there were differences in the number of TUNEL-stained cells reflecting the decrease in infarct size. Thus, ischemic brain injury activates PARP and contributes to cell death most likely by NAD depletion and energy failure, although the authors have not excluded a role for PARP in apoptotic cell death at earlier or later stages in ischemic cell death. Inhibitors of PARP activation could provide a potential therapy in acute stroke.

Animals↗

Reduction of Staphylococcus aureus in atopic skin lesions with acid electrolytic water--a new therapeutic strategy for atopic dermatitis.

The subjects studied were 22 pediatric patients newly diagnosed with atopic dermatitis (AD); 11 were treated with acid electrolytic water (AEW), which has a strong bactericidal activity (AEW group), and the other 11 with tap water (placebo group). AEW or tap water, 1 ml/cm2 (body surface area), was sprayed on their skin lesions with a spray gun each twice a day for a week. There were no significant differences between the two groups in regard to sex, age, serum IgE, peripheral eosinophil counts, grading scores of AD, and duration of AD. The study was designed as a randomized, placebo-controlled, double-blind clinical trial. Colony counts of Staphylococcus aureus on skin lesions in the AEW group, both 3 min after spraying (P < 0.05) and after 1 week of skin treatment (P < 0.01), were significantly decreased as compared with colony counts before treatment, while there was no significant difference in the placebo group before and after treatment. Grading scores of AD also decreased in the AEW group (P < 0.01), but not in the placebo group. Both the subjects' guardians' evaluation and a referee physician's evaluation of treatment effect were significantly higher in the AEW group than in the placebo group (P < 0.01). AEW may be potentially effective in preventing a staphylococcal chronic inflammation in AD because of its strong bactericidal activity.

Acids↗

Magnetic resonance imaging of sequelae of temporal lobe herniation secondary to traumatic acute subdural hematoma: Kernohan's notch and posterior cerebral artery territory infarctions contralateral to the supratentorial lesion--case report.

A 16-year-old girl presented with left hemiparesis and right oculomotor nerve paresis due to temporal lobe herniation resulting from a traumatic acute subdural hematoma secondary to a head injury. Computed tomography revealed a subdural hematoma in the right frontotemporal regions and midline structures shifted to the left. She became comatose and underwent an emergency operation. The hemiparesis and newly manifested homonymous hemianopsia on the right side persisted after surgery. Postoperative magnetic resonance imaging showed Kernohan's notch in the cerebral peduncle and infarctions in the occipital lobe and posterolateral part of the thalamus on the left side, contralateral to the supratentorial lesion.

Adolescent↗

A finite element model of the human face. Stress distribution around the chin due to articulation of the five vowels in Japanese.

In this study the authors set out to investigate the stress distribution around the chin due to articulation, and to discuss whether the calculated stresses can cause bone remodeling. A finite element model of facial soft tissue was constructed and movements related to the articulation of the five basic Japanese vowel sounds were reproduced individually on the model. The stress distribution of each vowel depended on the shapes formed by the lips and the degree of mandibular opening. Stresses increased with the strain on the soft tissue of the lips. It seemed unlikely that the calculated stress alone was sufficient to produce a hypertrophic increase in modeling. However, it seemed that muscle forces might produce an effective strain load with a range sufficient to cause bone remodeling by accumulation of stresses around the chin.

Biomechanical Phenomena↗

Studies of temporomandibular joint sounds; Part 4. Phase relations of TMJ sounds and jaw movement.

A study was conducted to investigate the timing relationship of temporomandibular joint (TMJ) sounds during mandibular movement, as evaluated by the location of the condyle, in relation to the articular fossa using axiograph recording. TMJ sounds during jaw opening and closing occurred over a wide range: opening sounds were observed within a range of 41-100% of maximum opening, while closing sounds occurred within 1-80% of maximum opening. In calculating the peak frequency of the joint sounds, it was noted that there was no correlation between the timing of the sound and its peak frequency. This study revealed that the acoustic characteristics of TMJ sounds may be unaffected by the location of the condyle.

Auscultation↗

Antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro.

We investigated the antimicrobial effects of phototherapy and photochemotherapy in vivo and in vitro. First, Staphylococcus aureus samples were obtained using stamp agar medium from inflammatory lesions of 29 adult patients with atopic dermatitis before and after a single photochemotherapy. Therapy was oral PUVA (30 mg 8-methoxypsoralen, 8MOP plus 5J/cm2 UVA), topical PUVA (0.3% 8MOP plus 200 mJ/cm2 UVA) or UVB (80 mJ/cm2) irradiation. The number of S. aureus on the lesions was significantly reduced, even after a single treatment with all therapies. Reductions (mean +/- SD) were 69.3 +/- 26.9%, 76.3 +/- 31.3% and 83.8 +/- 18.5%, respectively. Secondly, we investigated the effect of PUVA (0.001% 8MOP plus 10, 20, 30, 40, or 50 mJ/cm2 UVA) and UVB (10, 30, 50, or 100 mJ/cm2) irradiation on the proliferation of S. aureus in vitro. PUVA and UVB treatment markedly inhibited the proliferation in a dose-dependent manner. These results seem to indicate the possibility that the antimicrobial effect of UV radiation contributes to successful photochemotherapy in patients with atopic dermatitis.

Adult↗

Activity of eight fluoroquinolones against both methicillin-susceptible and -resistant Staphylococcus aureus isolated from skin infections.

The in vitro susceptibility of Staphylococcus aureus to eight fluoroquinolones, norfloxacin, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, tosufloxacin, sparfloxacin, and nadifloxacin was established by agar dilution tests, 71 isolates of methicillin-susceptible (MSSA) and 74 isolates of -resistant S. aureus (MRSA) isolated from skin infections. Among all of the fluoroquinolones, nadifloxacin exhibited the lowest MIC for both MSSA and MRSA. In addition, there were no resistant S. aureus, neither MSSA and MRSA, to nadifloxacin. With the exception of nadifloxacin, the incidence of MRSA resistant to fluoroquinolones has gradually increased in recent years. Over half of the MRSA strains were resistant to norfloxacin, ofloxacin, enoxacin, ciprofloxacin, and lomefloxacin.

Anti-Infective Agents↗

Staphylococcus aureus isolated from nostril anteriors and subungual spaces of the hand: comparative study of medical staff, patients, and normal controls.

An epidemiologic investigation of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (S. aureus) colonization was conducted at Kansai Medical University Hospital between 1990 and 1991. The incidence of nasal and subungual positivity for S. aureus was examined in a total of 156 subjects including inpatients, physicians, and nurses at a ward for dermatology, plastic surgery, and emergency patients, outpatients with atopic dermatitis and other skin diseases, and normal controls. Inpatients were most heavily colonized with MRSA (40.8%), but S. aureus colonization was most frequent in outpatients with atopic dermatitis (95.5%). Not only nostrils, which have been much discussed as a reservoir of S. aureus, but also subungual spaces seemed to be havens of S. aureus. Twelve out of 22 atopic dermatitis patients were positive for S. aureus on skin regions, and coagulase and phage testing showed a correlation between the nasal and skin-colonizing S. aureus. Coagulase type II and phase type NT (not typable) were the predominant types of S. aureus, including MRSA.

Dermatitis, Atopic↗

Studies of temporomandibular joint sounds Part 3. The clinical usefulness of TMJ Doppler.

Doppler auscultation as applied to internal derangements of the TMJ has been developed in recent years. Possible clinical use of TMJ Doppler auscultation was examined by separating the signals into their spectral components, and comparing the results with those of the conventional sound amplification system (CSAS). Observing frequency component changes with time, similar observations were made using CSAS and TMJ Doppler. However, noises found in TMJ Doppler sonograms were markedly reduced in comparison with those found using CSAS. Ultrasonic waves have high directivity, and pass through soft tissue and fluid; however they have difficulty passing through air, and this may decrease the recording noise. TMJ Doppler can be applied to record movements of the condyle because changes in the receiving frequency indicate the movement of an observed object with precision.

Adult↗

A study of temporomandibular joint sounds. Part 2. Acoustic characteristics of joint sounds.

In an attempt to gain a better understanding of temporomandibular joint (TMJ) sounds, we recorded joint sounds from 14 non-orthodontically treated dental students, analyzed the acoustic characteristics of the TMJ sounds, and correlated the sound characteristics with axiographic features, morphologic observations of X-ray images and clinical history. The group with a low peak frequency (< 500 Hz) of the opening click had a shorter history of subjective joint sound, a longer distance between the opening and closing curves, and a low rate of TMJ transformation. For the closing click, the history of subjective joint sounds tended to be longer when the duration of the wave was short. Acoustic analysis of TMJ sounds could be an aid to the differential diagnosis of temporomandibular disorders, although it is difficult to deduce the clinical history and internal deformities of the TMJ based solely on acoustic characteristics.

Auscultation↗