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Y Iwamoto

Publications and source records attributed to Y Iwamoto.

At least 19 recordsLinked to original sources
PubMed1997

Investigation of morphological change of lateral and midline fluid percussion injury in rats, using magnetic resonance imaging.

OBJECTIVE: Investigating the time course of morphological changes in experimental traumatic brain injury (TBI) in vivo helps to clarify the mechanism of TBI and develop new therapeutic modalities. We examined the morphological changes in experimental TBI, using magnetic resonance imaging (MRI) in a rat model. METHODS: We produced lateral fluid percussion injury (LFP) and midline fluid percussion injury (MFP) in rats, using the Yamaki fluid percussion device. The rats were divided into four groups: LFP, MFP, sham LFP, and sham MFP. MRI was performed with a 4.7-T magnetic resonance apparatus 2 days and 90 days after the induction of injury. T1-, T2-, and T2- weighted images were obtained using a surface coil. RESULTS: Hemorrhage, contusion, and brain edema in LFP models were detected on the 2nd day after injury, and the necrotic tissue was absorbed and replaced by cerebrospinal fluid on the 90th day. In MFP animals, we detected a small hemorrhage in the corpus callosum with minimal brain edema around the hemorrhage on the 2nd day after injury, and on the 90th day, enlarged ventricles and cisterns were observed, indicating brain atrophy. CONCLUSION: MRI, therefore, is useful for plotting morphological changes in experimental TBI in vivo. We report the novel and clinically important finding of brain atrophy after experimental TBI.

Animals↗
PubMed1996

A quantitative assay using basement membrane extracts to study tumor angiogenesis in vivo.

We describe a quantitative assay for assessing tumor angiogenesis in vivo using basement membrane extracts (Matrigel). Nude mice were injected s.c. with liquid Matrigel mixed with HT1080 human fibrosarcoma cells. Since Matrigel rapidly forms a solid gel at body temperature, the gel containing tumor cells can be removed immediately and then processed for histological studies. Tumor angiogenesis was monitored quantitatively by measuring both the number and the total area of neovessels present in the gels using an image analyzer, which could be achieved approximately 72 hr later. Furthermore, HT1080 cell-conditioned medium, which may contain various tumor-derived factors, promoted the basement membrane degradation, migration, proliferation and tube formation of endothelial cells in vitro, as did Matrigel, although to a lesser extent. In addition, Northern blot analysis demonstrated that the amount of vascular endothelial growth factor (VEGF) mRNA in HT1080 cells was much higher than that in human fibroblasts or NIH3T3 cells. Our results suggest that angiogenesis observed in our assay may be due to the synergic effects of tumor angiogenic factors such as VEGF, and Matrigel. The advantages of our assay are: 1) it is possible to assess early angiogenesis quantitatively; and 2) this assay may be applicable for screening anti-angiogenic therapeutic agents to be used against human neoplasms.

3T3 Cells↗
PubMed1996

Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1.

Signal transducers and activators of transcription (STAT) proteins can be conditionally activated in response to epidermal growth factor (EGF) and interferon (IFN)-gamma. STAT activation was correlated with cell growth inhibition in response to EGF and IFN-gamma. Activated STAT proteins specifically recognized the conserved STAT-responsive elements in the promoter of the gene encoding the cyclin-dependent kinase (CDK) inhibitor p21 WAF1/CIP1 and regulated the induction of p21 messenger RNA. IFN-gamma did not inhibit the growth of U3A cells, which are deficient in STAT1, but did inhibit the growth of U3A cells into which STAT1 alpha was reintroduced. Thus, STAT1 protein is essential for cell growth suppression in response to IFN-gamma. The STAT signaling pathway appears to negatively regulate the cell cycle by inducing CDK inhibitors in response to cytokines.

Base Sequence↗
PubMed1996

Increased expression of brain-derived neurotrophic factor but not neurotrophin-3 mRNA in rat brain after cortical impact injury.

Levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) mRNA expression were measured in a rodent model of traumatic brain injury (TBI) following unilateral injury to the cerebral cortex. To obtain reliable data on the co-expression of neurotrophin genes, adjacent coronal sections from the same rat brains were hybridized in situ with BDNF and NT3 cRNA probes. BDNF mRNA increased at 1,3, and 5 hr after unilateral cortical injury in the cortex ipsilateral to the injury site and bilaterally in the dorsal hippocampus. NT3 mRNA did not change significantly following injury. Our results suggest that TBI produces rapid increases in BDNF mRNA expression in rat brain without changes in NT3 mRNA expression, a finding which differs from studies of ischemia and seizures. It is possible that increased levels of BDNF mRNA rather than NT3 are important components of pathophysiological responses to TBI.

Analysis of Variance↗
PubMed1996

Liposome-mediated BDNF cDNA transfer in intact and injured rat brain.

We examined the temporal profile of the expression of brain-derived neurotrophic factor (BDNF) cDNA containing a viral promotor following the injection of liposome cDNA complexes into the intact and traumatically injured rat brain. In situ hybridization and PCR confirmed the presence of injected BDNF cDNA for at least 6 days after injection. A similar profile of BDNF cDNA was observed when it was injected following cortical impact injury. mRNA was also localized around the injection areas. These results suggest that liposome-mediated delivery of neurotrophin cDNA may be a practical gene transfer method for treating traumatic brain injury.

Animals↗
PubMed1996

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on neuropeptide metabolism in the rat brain.

The effect of a novel prolyl endopeptidase (PEP) inhibitor, (S)-2-[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl] carbonyl]-N-(phenylmethyl)-1-pyrrolidine-carboxamide (JTP-4819), on neuropeptide metabolism was investigated in the rat brain. JTP-4819 exhibited a strong in vitro inhibitory effect on cortical and hippocampal PEP activity, with the IC50 values being approximately 0.58 +/- 0.02 and 0.61 +/- 0.06 nM, respectively. JTP-4819 also inhibited the in vitro degradation of substance P (SP), arginine-vasopressin (AVP), and thyrotropin-releasing hormone (TRH) by rat brain supernatants, with the IC50 values being respectively 3.4, 2.1, and 1.4 nM in the cerebral cortex and 3.3, 2.8, and 1.9 nM in the hippocampus. Oral administration of JTP-4819 at doses of 1 and 3 mg/kg increased SP-like immunoreactivity (LI) and AVP-LI in the cerebral cortex. JTP-4819 also increased hippocampal SP-LI and AVP-LI at doses of 1 and 3 mg/kg, as well as hippocampal TRH-LI at a dose of 3 mg/kg. These findings suggest that JTP-4819 inhibited the degradation of SP, AVP, and TRH in the rat brain secondary to the inhibition of PEP, and thus increased cortical and hippocampal SP-LI and AVP-LI as well as hippocampal TRH-LI.

Administration, Oral↗
PubMed1996

Spatial coordination by descending vestibular signals. 2. Response properties of medial and lateral vestibulospinal tract neurons in alert and decerebrate cats.

Spatial response properties of medial (MVST) and lateral (LVST) vestibulospinal tract neurons were studied in alert and decerebrate cats during sinusoidal angular rotations of the whole body in the horizontal and many vertical planes. Of 220 vestibulospinal neurons with activity modulated during 0.5-Hz sinusoidal rotations, 200 neurons exhibited response gains that varied as a cosine function of stimulus orientation and phases that were near head velocity for rotation planes far from the minimum response plane. A maximum activation direction vector (MAD), which represents the axis and direction of rotation that maximally excites the neuron, was calculated for these neurons. Spatial properties of secondary MVST neurons in alert and decerebrate animals were similar. The responses of 88 of 134 neurons (66%) could be accounted for by input from one semicircular canal pair. Of these, 84 had responses consistent with excitation from the ipsilateral canal of the pair (13 horizontal, 27 anterior, 44 posterior) and 4 with excitation from the contralateral horizontal canal. The responses of the remaining 46 (34%) neurons suggested convergent inputs. The activity of 38 of these was significantly modulated by both horizontal and vertical rotations. Twelve neurons (9%) had responses that were consistent with input from both vertical canal pairs, including 9 cells with MADs near the roll axis. Thirty-two secondary MVST neurons (24%) had type II yaw and/or roll responses. The spatial response properties of 18 secondary LVST neurons, all studied in decerebrate animals, were different from those of secondary MVST neurons. Sixteen neurons (89%) had type II yaw and/or roll responses, and 12 (67%) appeared to receive convergent canal pair input. Convergent input was more common on higher-order vestibulospinal neurons than on secondary neurons. These results suggest that MVST and LVST neurons and previously reported vestibulo-ocular neurons transmit functionally different signals. LVST neurons, particularly those with MADs close to the roll axis, may be involved in the vestibular-limb reflex. The combination of vertical and ipsilateral horizontal canal input on many secondary MVST neurons suggests a contribution to the vestibulocollic reflex. However, in contrast to most neck muscles, very few neurons had maximum vertical responses near pitch.

Animals↗
PubMed1996

Sensitization interval and administration method alter the effect of 15-deoxyspergualin on heart transplantation in sensitized recipient rats.

We evaluated the effect of 15-deoxyspergualin (DSG) on accelerated rejection. Brown Norway rats (BN) served as organ donors and Lewis rats (LEW) as recipients. In an accelerated rejection model, after a LEW rat was sensitized with BN skin, a BN heart was transplanted. Various intervals between sensitization and heart transplantation were examined. The heart allografts in sensitized recipients were rejected earlier than those in unmodified recipients regardless of the sensitization interval. DSG (2.5 mg/kg per day), given to the recipients during the sensitization phase, significantly prolonged graft survival compared with the untreated hosts when the sensitization interval was short. When the recipients were treated with DSG after heart transplantation, heart graft survival was significantly prolonged regardless of the sensitization interval. Flow cytometric analysis and complement-dependent cytotoxicity tests revealed that DSG suppressed antidonor antibody formation and the postoperative administration of DSG significantly decreased the proliferation of B cells when the sensitization interval was short and the proliferation of class II antigen-positive cells when the sensitization interval was long.

Animals↗
PubMed1996

Sparfloxacin phototoxicity: potential photoaugmentation by ultraviolet A and B sources.

Sparfloxacin, a quinolone antibacterial agent, frequently elicits photosensitive skin reactions. Our clinical studies of patients treated with sparfloxacin have demonstrated that this photosensitivity is primarily phototoxic and that a marked erythematous response is induced by sequential irradiation with ultraviolet A (UVA) and B (UVB) but not UVA or UVB alone, suggesting potential synergism between UVA and UVB. We evaluated the phototoxicity of this agent using in vitro DNA breaking activity and in vivo murine cutaneous responses. Sparfloxacin induced DNA strand breaks in vitro and converted the supercoiled closed circular form of plasmid DNA to the open circular form by its photodynamic action. In mice, the topical application of sparfloxacin and subsequent irradiation with UVB, but not UVA, induced ear swelling responses. However, the UVB-induced ear swelling response was augmented by irradiation with UVA before or after UVB exposure. Such interaction between UVA and UVB in the production of ear swelling was further confirmed by systemic administration of sparfloxacin. Our study suggests that sparfloxacin is a unique phototoxic agent in that photosensitivity dermatitis is evoked by photoaugmentation between UVA and UVB.

Animals↗
PubMed1996

The influence of high and low molecular weight chitosan on colonic cell proliferation and aberrant crypt foci development in CF1 mice.

The effect of dietary chitosan, a fibre of animal origin, on the induction and development of colonic precursor lesions was determined in CF1 mice. Over a 2-wk pretreatment period, one group of mice was given azoxymethane (four injections of 5 mg/kg body weight) and the other was treated with saline. Subsequent to carcinogen or saline pretreatment mice were randomized into one of three dietary groups: (i) control AIN-76 diet; (ii) control AIN-76 diet with 2% low molecular weight chitosan (LMWC); or (iii) control AIN-76 diet with 2% high molecular weight chitosan (HMWC). Mice were maintained on this diet for 6 wk. Mice fed diet containing HMWC had significant reductions in the number of aberrant crypt foci, cell proliferation, crypt height and crypt circumference in the colonic epithelium (P < 0.05). In mice given diet supplemented with LMWC there was a trend towards reduced numbers of aberrant crypts, as well as decreased crypt height and circumference. The results of this study indicate that dietary chitosan reduces the incidence of early preneoplastic markers of colon carcinogenesis, as indicated by aberrant crypts and mitotic figures and altered crypt morphometrics in the murine colon. Molecular range and viscosity of the chitosan may influence the efficacy of this activity.

Animals↗
PubMed1996

Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia.

Chordoma shows various degrees of atypia histologically, however, the relationship between the histological features and the biological behavior still remains controversial. The authors subclassified 17 specimens with chordoma into two groups (ie, trabecular type showing a trabecular patterns and solid type mainly consisting of a diffuse proliferation of tumor cells). The histological grading was performed according to the degree of nuclear atypia on a scale of 1 to 3. Using DNA flow cytometric and immunohistochemical techniques, both the proliferative index (% S + G2 + M phase) and the MIB-1 labeling index (LI) of the tumor cells were estimated regarding their proliferative activities. In addition, p53 overexpression was also investigated using immunohistochemical techniques. There were eight (47.1%) specimens of trabecular type and nine (52.9%) of solid type. In nine specimens of solid type, those with higher nuclear atypia (grade 2 or 3) were significantly more frequent (five specimens, 55.6%) than in trabecular type in which all of the eight specimens were grade 1 (P = 0.44). The proliferative index was significantly higher in grade 2 or 3 lesions than in grade 1 lesions (P = .014), and the MIB-1 LI tended to be higher in solid type than in trabecular (P = .088). p53 overexpression was detected in two specimens of solid type, and the MIB-1 LI in these two specimens was significantly higher (P = .037) than that in the specimens without p53 overexpression. It was considered that the preceding anaplastic histological features, including either diffuse proliferation or high grade nuclear atypia, together with p53 overexpression, were thus closely related to the proliferative activities in chordomas.

Adolescent↗
PubMed1996

Functional connectivity of the superior colliculus with saccade-related brain stem neurons in the cat.

Effects of stimulation of the superior colliculus on saccade-related brain stem neurons were studied in the alert cat. Extracellular recordings were made from medium-lead burst neurons (MLBNs), omnipause neurons (OPNs) and burster-driving neurons (BDNs) in the paramedian pontomedullary region rostral and caudal to the abducens nucleus. MLBNs were activated from the contralateral superior colliculus with monosynaptic latencies when single-pulse stimulation was given during saccades or ipsilateral head rotation, although this activation was not observed during fixation periods. The caudal SC was more effective than the rostral SC in monosynaptic activation of MLBNs. Most OPNs were also activated monosynaptically from the SC. In contrast to MLBNs, the activation of OPNs was more frequently induced from the rostral SC than from the caudal SC. Stimulation of the caudal SC often induced suppression of spikes in OPNs. BDNs received excitation from the ipsilateral SC through a di- or trisynaptic pathway. Like MLBNs, BDNs tended to receive stronger input from the caudal SC than the rostral SC. Results indicate the existence of tectofugal excitatory pathways to MLBNs and BDNs and an inhibitory pathway to OPNs. It seems likely that these pathways originate from saccade-related burst cells in the SC. Since excitation of BDNs and inhibition of OPNs increase the excitability of MLBNs, all of these pathways may contribute to burst activity in MLBNs and thereby saccade generation. Results also support the current idea that cells in the rostral SC may participate in fixation by activating OPNs.

Animals↗
PubMed1996

Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-Ile-Gly-Ser-Arg (YIGSR).

A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Co-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT 1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(AcY1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity in tumour cells in vivo. The effect of the peptides on angiogenesis and tumour growth respectively were evaluated by counting areas of neovessels and weighing tumours after the s.c. implantation of HT1080 cells with basement membrane extracts and the peptide into nude mice. Co-injection of 0.5 mg per mouse of AC-Y16 s.c. with HT1080 cells inhibited angiogenesis and tumour growth by 92% (P<0.05) and 76% (P<0.05) respectively, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-Y1) inhibited angiogenesis and tumour growth by 40% (P<0.05) and 9% (P>0.05) respectively. It can be inferred from these data that anti-tumour effects of Ac-Y16 are likely to result from anti-angiogenesis. Intraperitoneal administration of Ac-Y16 was also effective in inhibiting angiogenesis, tumour growth and lung colonisation of HT1080 cells. It was concluded that the multimeric YIGSR-containing peptide, Ac-Y16, inhibits angiogenesis, tumour growth and experimental metastasis more than the monomeric form and that it is active when administered i.p., iv. and s.c.

Amino Acid Sequence↗
PubMed1996

Visual form agnosia in multiple sclerosis.

We report a case of multiple sclerosis with visual form agnosia and callosal syndromes. Initially, the patient's visual recognition of object form was severely disturbed at the perceptual stage, in association with left-sided ideomotor apraxia and agraphia. Magnetic resonance imaging showed large white matter lesions in the bilateral frontal and occipital lobes, the latter extending to the occipitotemporal junction, and widespread corpus callosum lesions. Over the course of one year follow-up, neuropsychological examinations indicated that the patient's visual recognition defects occurred not only at the early substage of form perception, but also at the stage of reproducing the shape of objects from visual memory store. The present case suggests that neural connections between the striate cortex and occipitotemporal visual areas are crucial for both the perceptual and associative stages of visual object recognition.

Agnosia↗
PubMed1996

Monosynaptic activation of medium-lead burst neurons from the superior colliculus in the alert cat.

1. Extracellular recordings were made from medium-lead burst neurons (MLBNs) in the paramedian pontomedullary reticular formation rostral and caudal to the abducens nucleus in the alert cat. 2. Single-pulse stimulation of the contralateral superior colliculus during intersaccadic intervals evoked no response in most MLBNs. When collicular stimulation was applied at the beginning of saccades, spikes of MLBNs were consistently evoked with short latencies. The shortest latency was 0.8 ms, indicating monosynaptic activation of MLBNs from the superior colliculus. 3. Results suggest that monosynaptic excitatory effects from the colliculus are concealed by inhibitory input from omnipause neurons (OPNs) during intersaccadic intervals and that the monosynaptic collicular activation is disclosed when this inhibition is removed by a pause in OPN activity at the beginning of saccades.

Abducens Nerve↗
PubMed1996

In vivo evaluation of antiplatelet agents in gerbil model of carotid artery thrombosis.

BACKGROUND AND PURPOSE: Antiplatelet agents are widely used for the prevention of ischemic stroke. However, their effects on thrombus formation have rarely been evaluated in experimental animals in vivo. We introduce methods for evaluating antithrombotic action in gerbils and the effects of several antiplatelet agents on thrombus formation. METHODS: In gerbils 8 to 10 weeks of age, we tightly compressed the unilateral common carotid artery for 2 minutes using the device prepared for this purpose to damage the endothelium. Thrombus formation in the damaged artery was observed directly through the microscope for 30 minutes. In six animals, the damaged artery was examined immediately after the experiments by electron microscopy. We studied the effects of antiplatelets by injecting the drugs intravenously 10 minutes before endothelial damage. RESULTS: In control studies, 70% to 90% of animals developed thrombi after arterial compression. The electron microscopic examination displayed endothelial damage in association with platelet thrombus at the damaged site. Administration of 2 mg/kg aspirin, 3 and 10 mg/kg ticlopidine, and 0.3 and 1.0 mg/kg ibudilast, a novel prostacyclin accelerator, decreased the frequency of thrombus formation significantly, whereas 20 mg/kg aspirin and 20 mg/kg dipyridamole failed to decrease thrombus formation. CONCLUSIONS: This model is considered useful for evaluating the antithrombotic effects of drugs because of its feasibility and high reproducibility. The present results support the view that a lower dose of aspirin may prevent cerebral vascular accidents as efficiently as a higher dose of aspirin.

Animals↗
PubMed1996

Multimodal evoked potentials in Alzheimer's disease and Binswanger's disease.

Somatosensory evoked potentials (SEPs), brainstem auditory evoked potentials (BAEPs), visual evoked potentials (VEPs), and auditory event-related potentials (ERPs) were studied in 15 patients with Alzheimer's disease (AD), eight patients with Binswanger's disease (BD), and 15 normal subjects. Patients with BD showed significant prolongation of the interpeak latency between N13 and N20 (N13-N20) and N20-P40 of SEPs as compared with the normal controls, whereas patients with AD only demonstrated significant prolongation of N20-P40. The interpeak latency between waves I and V of BAEPs in patients with both AD and BD was significantly longer than that of controls. There were no significant differences in P100 latency of VEPs among these three groups. Both groups with dementia showed significant prolongation of N200 and P300 latencies of ERPs compared with normal controls. In addition, patients with AD showed significant prolongation of P200 latency. We conclude that these two dementing diseases have different electrophysiologic features that may be related to their underlying pathogenetic mechanisms. Furthermore, the measurement of multimodal evoked potentials may be helpful in the differential diagnosis of AD and BD.

Aged↗