Akinori Shimada

Azabu University, Sagamihara, Kanagawa, Japan

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Publications (184)286.39 Total impact


  • No preview · Article · Apr 2015 · Leukemia Research
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    ABSTRACT: Introduction: Exposure to Asian sand dust (ASD) is associated with enhanced pulmonary morbidity and mortality, and the reporting of such cases has rapidly increased in East Asia since 2000. The purpose of the study was to assess chronic lung toxicity induced by ASD. Material and methods: A total of 174 ICR mice were randomly divided into 5 control and 17 exposure groups. Suspensions of low dose (0.2, 0.4 mg) and high dose (3.0 mg) of ASD particles in saline were intratracheally instilled into ICR mice, followed by sacrifice at 24 hours, 1 week, and 1, 2, 3 and 4 months after instillation. Paraffin sections of lung tissues were stained with hematoxylin and eosin and by immunohistochemistry to detect α-smooth muscle actin, collagen III, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), CD3, CD20, immunoglobulin G, interleukin-1β and inducible nitric oxide synthase. Results: A lung histological examination revealed similar patterns in the lesions of the groups treated with high (3.0 mg) or low dose (0.4 mg) of ASD. Acute inflammation was observed 24 h after treatment and subsided after 1 week; persistent granulomatous changes were observed at 2 months, focal lymphocytic infiltration at 3 months, and granuloma formation at 4 months. An increase in the size of granulomatous lesions was observed over time and was accompanied by collagen deposition in the lesions. The cytoplasm of macrophages in inflammatory lesions showed positive immunolabeling for MMP-9 at 24 h, 1 and 2 months after instillation of 3.0 mg of ASD. Positive immunolabeling for TIMP-1 was demonstrated in the cytoplasm of macrophages at 2 and 4 months after instillation of 3.0 mg of ASD. These findings suggest association between the expression of MMP-9 and TIMP-1 with the development of lung granulomatous lesions. Conclusions: These findings suggest that collagen deposition resulting from the altered regulation of extracellular matrix is associated with granuloma formation in the lungs of mice treated with ASD.
    Preview · Article · Feb 2015 · Folia Histochemica et Cytobiologica
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    ABSTRACT: Sand storms in Mongolia have increased in frequency and scale, resulting in increased exposure of the inhabitants of Asian countries, including Japan and Korea, to Asian sand dust (ASD), which results in adverse effects on the respiratory system. However, there is no information on the health risks of severe sand storms in domestic animals in Mongolia. The aim of the study was to investigate the effects of sand dust particles on the respiratory organs, including the lungs and tracheobronchial lymph nodes, of sheep and goats exposed to severe sand storms in Mongolia. Seven adult sheep and 4 adult goats that had been exposed to sand storms and 3 sheep with no history of exposure were included in this study. Lung tissues and tracheobronchial lymph nodes were subjected to histopathological and immunohistochemical examination. The mineralogical contents of the lungs and lymph nodes were determined using inductively coupled plasma atomic emission spectroscopy. Fibrosis and granulomatous lesions comprising macrophages containing fine sand dust particles were observed exclusively in the lungs of sheep and goats exposed to sand storms. The activity of macrophages was also demonstrated by the presence of IL-6, TNF, and lysozyme. In addition, silicon, which is the major element of ASD (kosa aerosol), was detected exclusively in the lung tissues of the exposed animals. Our findings suggest that exposure to sand dust particles may affect the respiratory systems of domestic animals during their relatively short life span.
    Preview · Article · Oct 2014 · Folia Histochemica et Cytobiologica
  • M Tanaka · K Inoue · Y Kitamura · A Shimada · H Takano
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    ABSTRACT: Although Sho-seiryu-to (SST), used as a traditional herbal (Kampo) medicine mainly in China and Korea, is shown to have immunomodulating potential, such as an anti-allergic one, its underlying mechanism has not been completely clarified. To partially address the issue, we explored its effects on allergen-exposed mononuclear cells. Male balb/c mice were intraperitoneally administered ovalbumin (OVA: 20 μg) plus alum or vehicle twice (Day 0 and Day 14). At Day 21, mice were sacrificed and splenocytes (mononuclear cells) were isolated and cultured in the presence or absence of OVA with or without SST. Thereafter, helper T-related cytokines in the culture supernatants were evaluated by means of ELISA. Protein level of interferon-γ was lower than 5.0 pg/mL in the supernatants from OVA– non-exposed or -exposed mononuclear cells in the presence or absence of OVA stimulation. On the other hand, SST induced the cytokine from both types of mononuclear cells in the presence (P < 0.05) or absence of OVA stimulation as compared to corresponding control. By contrast, interleukin (IL)-4 level tended to be decreased by SST in OVA-non-exposed mononuclear cells as did IL-13 in both non-exposed and exposed mononuclear cells as compared to vehicle. In conclusion, immunoregulating efficacy by SST on allergy-prone subjects may include, at least in part, restoring helper T balance mainly through hyperproduction of IFN-γ against mononuclear cells such as lymphocytes.
    No preview · Article · Oct 2014 · International journal of immunopathology and pharmacology
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    ABSTRACT: Recurrent seizures without interictal resumption (status epilepticus) have been reported to induce neuronal death in the midline thalamic region that has functional roles in memory and decision-making; however, the pathogenesis underlying status epilepticus-induced thalamic neuronal death is yet to be determined. We performed histological and immunohistochemical studies as well as cerebral blood flow measurement using 4.7 tesla magnetic resonance imaging spectrometer on midline thalamic region in Sprague–Dawley rats (n = 75, male, 7 weeks after birth, body weight 250–300 g) treated with intraperitoneal injection of kainic acid (10 mg/kg) to induce status epilepticus (n = 55) or normal saline solution (n = 20). Histological study using paraffin-embedded specimens revealed neuronal death showing ischemic-like changes and Fluoro-Jade C positivity with calcium deposition in the midline thalamic region of epileptic rats. The distribution of neuronal death was associated with focal loss of immunoreactivity for excitatory amino acid transporter 2 (EAAT2), stronger immunoreaction for glutamate and increase in number of Iba-1-positive microglial cells showing swollen cytoplasm and long processes. Double immunofluorescence study demonstrated co-expression of interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) within microglial cells, and loss of EAAT2 immunoreactivity in reactive astrocytes. These microglial alterations and astrocytic EAAT2 downregulation were also observed in tissue without obvious neuronal death in kainic acid-treated rats. These results suggest the possible role of glutamate excitotoxicity in neuronal death in the midline thalamic region following kainic acid-induced status epilepticus due to astrocytic EAAT2 downregulation following microglial activation showing upregulation of IL-1β and iNOS.
    Full-text · Article · Aug 2014 · Neuropathology
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    ABSTRACT: In the last five years in western Mongolia, a neurological disorder and resultant economic loss have developed in goats, sheep, cattle and horses: association of the disease with ingestion of Oxytropis glabra, a toxic plant, was suggested. Affected goats showed neurological signs, including ataxia, incoordination, hind limb paresis, fine head tremor, and nystagmus. Three goats, one with moderate clinical signs and the other two with severe clinical signs, were necropsied and examined to describe and characterize the histologic, immunohistochemical and ultrastructural lesions. Although no gross pathological changes were observed in a variety of organs including the central nervous system of these goats, microscopic examination of the cerebellum demonstrated degenerative changes in all these goats, such as vacuolar changes and loss of Purkinje cells, torpedo formation in the granular layer, increased number of spheroids in the cerebellar medulla, and loss of axons and myelin sheaths of Purkinje cells. The chemical analysis of the dried plant detected 0.02-0.05% (dry weight basis) of swainsonine. This is the first report describing the clinical and pathological findings in Mongolian goats suspected to be affected by O. glabra poisoning.
    Full-text · Article · Feb 2014 · Journal of Veterinary Medical Science
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    ABSTRACT: Abstract The effects of environmental pollutants on airway clearance have not been well elucidated. This study examined mucociliary transport using different sized-fluorescent particles on polarized human airway epithelial cells which were maintained in an air-liquid interface (ALI) culture system. The effects of hydrogen peroxide (H2O2) exposure on mucociliary transport were also investigated. The movement of fluorescent particles with diameters of 10-14 µm and 2.5-4.5 µm was observed by fluorescent microscopy as an index of the mucociliary transport. The mixture of the particles with two different sizes were propelled concentrically on the apical surface by the interaction of ciliary activity and mucus in the control condition, whereas H2O2 exposure for 24 h significantly inhibited the movement of the particles. The particle sizes did not affect their movement after the control or H2O2 exposure. These results suggest that particle tracking on polarized human airway epithelial cells is a useful experimental tool for the evaluation of the effect of environmental pollutants on mucociliary transport. In addition, reactive oxygen species may impair mucociliary transport, leading to the airway damage, and exacerbation of respiratory diseases.
    No preview · Article · Dec 2013 · Toxicology mechanisms and methods
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    ABSTRACT: Exposure to nanoparticles during pregnancy is a public concern, because nanoparticles may pass from the mother to the fetus across the placenta. The purpose of this study was to determine the possible translocation pathway of gold nanoparticles across the maternal-fetal barrier as well as the toxicity of intravenously administrated gold nanoparticles to the placenta and fetus. Pregnant ICR mice were intravenously injected with 0.01% of 20- and 50-nm gold nanoparticle solutions on the 16th and 17th days of gestation. There was no sign of toxic damage to the placentas as well as maternal and fetal organs of the mice treated with 20- and 50-nm gold nanoparticles. ICP-MS analysis demonstrated significant amounts of gold deposited in the maternal livers and placentas, but no detectable level of gold in the fetal organs. However, electron microscopy demonstrated an increase of endocytic vesicles in the cytoplasm of syncytiotrophoblasts and fetal endothelial cells in the maternal-fetal barrier of mice treated with gold nanoparticles. Clathrin immunohistochemistry and immunoblotting showed increased immunoreactivity of clathrin protein in the placental tissues of mice treated with 20- and 50-nm gold nanoparticles; clathrin immunopositivity was observed in syncytiotrophoblasts and fetal endothelial cells. In contrast, caveolin-1 immunopositivity was observed exclusively in the fetal endothelium. These findings suggested that intravenous administration of gold nanoparticles may upregulate clathrin- and cavelin-mediated endocytosis at the maternal-fetal barrier in mouse placenta.
    Full-text · Article · Nov 2013 · Journal of Veterinary Medical Science
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    ABSTRACT: It has been demonstrated that exposure to diesel exhaust (DE) is associated with the induction and exacerbation of respiratory disorders; however, the impacts of DE containing mainly nanoparticles have been less studied. We have previously demonstrated that inhalation exposure to nanoparticle-rich DE (NR-DE) exacerbated allergic pulmonary inflammation, in the context of enhanced local expression of proinflammatory molecules. However, the underlying mechanisms have not been fully elucidated. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative damage, particularly in DNA. This study examined the effects of NR-DE on 8-OHdG synthesis in the lung in the presence or absence of an allergen. Institute for Cancer Research (ICR) mice were exposed by inhalation to four different gas compositions (control air, low-concentration DE, high-concentration DE and high-concentration DE without particulate matter) for 8 weeks, in the presence or absence of repetitive intratracheal administration of ovalbumin (OVA). Thereafter, we assessed the levels of 8-OHdG synthesis and expression in the lungs by means of enzyme immunoassay (EIA) and immunohistochemistry. The EIA revealed that the level of 8-OHdG was significantly higher in the high-concentration NR-DE-exposed and allergen-sensitized/stimulated group compared with that in the control air-exposed and allergen-treated group. The immunohistochemistry results demonstrated that the level of immunoreactive 8-OHdG was higher in the NR-DE-exposed and allergen-treated lungs compared with that in the corresponding control air-exposed lungs. The results suggested that NR-DE exposure enhanced 8-OHdG formation in asthmatic lungs. This, at least in part, is involved in the NR-DE-mediated exacerbation of the allergic pathophysiology that was identified in our previous study.
    Preview · Article · Sep 2013 · Experimental and therapeutic medicine
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    ABSTRACT: Objective-To determine whether angiogenesis and microglial activation were related to seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Animals-Cadavers of 10 Shetland Sheepdogs from the same family (6 dogs with seizures and 4 dogs without seizures) and 4 age-matched unrelated Shetland Sheepdogs. Procedures-Samples of brain tissues were collected after euthanasia and then fixed in neutral phosphate-buffered 10% formalin and routinely embedded in paraffin. The fixed samples were sectioned for H&E staining and immunohistochemical analysis. Results-Evidence of seizure-induced neuronal death was detected exclusively in samples of cerebral cortical tissue from the dogs with familial epilepsy in which seizures had been observed. The seizure-induced neuronal death was restricted to tissues from the cingulate cortex and sulci surrounding the cerebral cortex. In almost the same locations as where seizure-induced neuronal death was identified, microvessels appeared longer and more tortuous and the number of microvessels was greater than in the dogs without seizures and control dogs. Occasionally, the microvessels were surrounded by oval to flat cells, which had positive immunohistochemical results for von Willebrand factor. Immunohistochemical results for neurons and glial cells (astrocytes and microglia) were positive for vascular endothelial growth factor, and microglia positive for ionized calcium-binding adapter molecule 1 were activated (ie, had swollen cell bodies and long processes) in almost all the same locations as where seizure-induced neuronal death was detected. Double-label immunofluorescence techniques revealed that the activated microglia had positive results for tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor receptor 1. These findings were not observed in the cerebrum of dogs without seizures, whether the dogs were from the same family as those with epilepsy or were unrelated to them. Conclusions and Clinical Relevance-Signs of angiogenesis and microglial activation corresponded with seizure-induced neuronal death in the cerebral cortex of Shetland Sheepdogs with familial epilepsy. Microglial activation induced by vascular endothelial growth factor and associated proinflammatory cytokine production may accelerate seizure-induced neuronal death in dogs with epilepsy.
    No preview · Article · May 2013 · American Journal of Veterinary Research
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    ABSTRACT: The purpose of this study was to investigate a possible translocation pathway of intratracheally instilled gold nanoparticles after the induction of acute pulmonary injury by Asian sand dust. ICR mice were intratracheally instilled with 800μg Asian sand particles (CJ-2 particles) 24h before instillation of 50-nm gold nanoparticles. Lungs from mice treated with Asian sand particles and gold nanoparticles showed an acute focal inflammation with an increased expression of proinflammatory cytokines (IL-6 and TNF-α) and oxidative stress markers (Cu/Zn SOD and iNOS) in alveolar macrophages, type I alveolar epithelial cells, and endothelial cells at the alveolar walls. Electron microscopy revealed a destruction of the alveolar walls with an increased number of endocytic vesicles in the cytoplasm of both type I epithelial cells and endothelial cells; gold nanoparticles were demonstrated in these endocytic vesicles. These findings suggest that translocation of the exposed nanoparticles may be enhanced in the lung tissues with acute inflammatory changes.
    No preview · Article · Apr 2013 · Experimental and toxicologic pathology: official journal of the Gesellschaft fur Toxikologische Pathologie
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    ABSTRACT: To study the subchronic and chronic lung effects of low dose of Diesel Exhaust Particles (DEPs), mice were intratracheally instilled with 50 μg of DEPs. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alteration were determined at 90, 120, 150 and 180 days after instillation. From BALF results, exposure to 50 μg of DEPs did not cause any pulmonary inflammation. However, mild to moderate pulmonary changes evidenced by multifocal DEPs laden alveolar macrophages (AMs) aggregation, type II alveolar cell proliferation, thickening of alveolar wall, interstitial fibrosis and edema were observed in treated mouse lungs. Basement (BM) damage detected by laminin immunohistochemistry and myofibroblast proliferation detected by smooth muscle actin immunoreactivity on the lungs remained in the alveolar region until chronic stage. Metallothionein expression in DEPs-treated mice occurred in lung epithelial cells and laden AMs, which correlated with lung lesions. These findings suggest that instillation of a low dose of DEPs causes mild to moderate pulmonary changes and tissue damage related to the existence of DEPs.
    No preview · Article · Mar 2013 · The Thai veterinary medicine
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    Z Anis · T Morita · K Azuma · H Ito · T Ito · A Shimada
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    ABSTRACT: The chicken and duck are important hosts of Newcastle disease virus (NDV) with distinctive responses to infection. NDV infection in ducks is often subclinical and chronic, while in chickens the infection is clinically apparent and transient. These differences may be due to in part to the host response to NDV infection. This study compares the histopathological changes in the spleen, thymus and bursa of Fabricius following infection with NDV in chickens and ducks. The 9a5b isolate of NDV was inoculated intranasally into specific pathogen-free chickens and Japanese commercial ducks. NDV nucleoprotein (NDV-NP) and interferon (IFN)-β were detected in tissues by immunohistochemistry (IHC), apoptosis was detected by haematoxylin and eosin staining, caspase-3 IHC and the TUNEL assay. Labelling of NDV-NP and lymphoid depletion were most marked in chicken tissues. The pattern of apoptosis in the spleen differed between chickens and ducks. In chickens there were numerous apoptotic cells in the peri-ellipsoidal white pulp and the peri-ellipsoidal, peri-arteriolar and peri-venous lymphoid sheaths, while apoptosis in duck spleens was mainly within the germinal centres. Lymphoid depletion was the main feature in the bursal and thymic tissues of chickens, but apoptosis was marked in these organs in ducks. Expression of IFN-β appeared earlier and was more intense in the tissues from ducks compared with those from chickens. The differences in IFN-β and NDV-NP expression may reflect the relative clinical severity of the infection in the two avian species.
    Full-text · Article · Jan 2013 · Journal of comparative pathology
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    ABSTRACT: Because precise information as to the toxicity of vanadium is required for practical use of vanadium compounds as antidiabetic drugs, we examined vanadium toxicity in mice fed normal diet or high-fat diet (C57BL/6N, male, 7 weeks) by oral administration of ammonium metavanadate (AMV) with a maximum dose of 20 mgV/kg/day. Marked lipid accumulation in hepatocytes, renal epithelial cells, and mucosal epithelial cells of the small and large intestines and severe degeneration, necrosis, and loss of mucosal epithelial cells in the small intestine were observed. These pathological changes were more severe in mice fed high-fat diet than mice fed normal diet, and the intensity of the changes increased with increase in the administered dose of AMV. By electron microscopy, the number and size of lipid droplets in hepatocytes were increased. In the small intestine, a TUNEL assay showed a decreased number of positive cells, and positive cells for acrolein immunohistochemistry were observed specifically in the mucosal epithelial cells indicating degeneration and necrosis in the AMV-treated group, suggesting that a possible factor responsible for cell necrosis in the small intestine could be oxidative stress. In conclusion, AMV may impair cellular lipid metabolism, resulting in lipid accumulation, and induce mucosal epithelial cell necrosis in the small intestine.
    Preview · Article · Dec 2012 · Toxicologic Pathology
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    Z Anis · T Morita · K Azuma · H Ito · T Ito · A Shimada
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    ABSTRACT: Lentogenic Newcastle disease viruses (NDVs), circulating among waterfowl, have the potential to become highly pathogenic by replication in chickens. The pathological studies that compare NDV infections in chickens and waterfowl are rare. The virulent 9a5b mutant NDV isolate was generated by passaging the lentogenic Goose/Alaska/415/91 NDV isolate in chickens. The pathogenesis of the virulent 9a5b mutant isolate is unknown in both chickens and waterfowl. In this study, the virulent 9a5b mutant NDV isolate was inoculated intranasally in 32-day-old specific pathogen-free white Leghorn chickens and Japanese commercial ducks. Unlike ducks, which remained clinically normal throughout the study, chickens had depression, gasping, oral discharges, and greenish-white soft feces. Gross and histologic lesion patterns as well as viral replication supported the differing clinical outcome. Ducks had slight inflammation mainly in respiratory and digestive tracts, whereas slight nonpurulent encephalitis, necrotizing pancreatitis, tubulointerstitial nephritis, and mild inflammation in respiratory and digestive tracts were detected in chickens. In agreement, interferon-beta (IFN-β)-immunopositive signals were more intense in lung tissue of ducks than that of chickens, and NDV replications were detected intensively in chicken tissues. These results suggest that the 9a5b mutant NDV isolate is more virulent in chickens, and slight histological lesions were induced in ducks even with virulent NDVs.
    Full-text · Article · Dec 2012 · Veterinary Pathology
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    ABSTRACT: Metallothionein (MT), a low-molecular-weight protein with a high affinity for divalent heavy metal ions, is involved in many pathophysiological processes, including metal homeostasis, detoxification, cell proliferation and protection against oxidative damage. We previously found that MT in gastric mucosa plays a role in protecting against Helicobacter pylori (H. pylori)-induced gastritis at the early stage of infection. H. pylori-induced chronic gastric inflammation is shown to be associated with gastric carcinogenesis. Thus, to examine whether gastric MT contributes to protection against H. pylori-induced chronic inflammation, we compared histological changes in the gastric mucosa of MT-null and the wild-type mice at 53 weeks after inoculation three times with H. pylori SS1. As a result, we observed disruption of the gastric mucosa in MT-null mice, but not in the wild-type mice, even at the late stage of H. pylori-infection. Evaluation of pathological changes in gastric specimens by the updated Sydney grading system revealed that scores related to chronic inflammation and polymorphonuclear cell activity were higher in infected MT-null mice than those in the wild-type mice. Furthermore, a higher score for metaplasia was also observed in the MT-null stomach. These results suggested that MT might be involved in protecting against H. pylori-induced gastric chronic inflammation associated with carcinogenesis.
    No preview · Article · Dec 2012 · The Journal of Toxicological Sciences
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    ABSTRACT: Endocytosis is the primary mechanism by which nanoparticles are translocated over the alveolar epithelium. The purpose of this study was to elucidate the association between endocytosis and the translocation of nanoparticles at the air-blood barrier (ABB). Gold colloid particles (diameter, 20 nm) were intratracheally instilled into male ICR mice. Fifteen minutes after instillation, localized accumulation of agglomerated gold particles was observed in the cytoplasm of macrophages, on the surface of alveolar epithelial cells (AECs), and in alveoli. Electron microscopy revealed particles in the vesicles of macrophages, on the surface of AECs, and in caveolae-like vesicles in type 1 AECs. Immunohistochemistry demonstrated positive immunolabeling for caveolin-1 in the ABB of untreated lungs as well as lungs treated with gold particles. Double immunofluorescence and immunoelectron microscopy revealed the presence of caveolin-1 in AECs in the untreated lungs. These results suggest that instilled gold colloid particles are internalized into the alveolar epithelium at the ABB by caveolae-mediated endocytosis, which is regarded as a physiological function of AECs.
    Preview · Article · Aug 2012 · Toxicologic Pathology
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    ABSTRACT: A cerebral vascular hamartoma was identified in the frontal lobe, striatum and thalamus of the right side of the brain of a male, 7-year-old Shih Tzu. Histologically, the lesion consisted of thin-walled vessels, which showed various sizes and occasionally contained fibrin thrombi. These vascular walls were composed of a single layer of fibromuscular tissue lined by flat endothelium with various amount of collagen, but devoid of large coat of smooth muscles and elastic tissue. Immunohistochemically, the lining endothelial cells were positive for von Willebrand Factor antibody. Neuropil between the vessels was stained with Klüver-Barrera stain, and positive for synaptophysin and GFAP antibodies. Based on these findings, the lesion was diagnosed as vascular hamartoma, which might resemble venous malformation in humans.
    No preview · Article · Jun 2011 · Journal of Veterinary Medical Science
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    ABSTRACT: Cadmium (Cd) causes renal dysfunction with damage to kidney proximal tubule cells; however, the precise mechanisms of the toxicity remain unclear. Previously, we found that the expression of Ube2d4 gene, which is a member of the ubiquitin-conjugating enzyme Ube2d family, is suppressed by Cd in NRK-52E rat renal tubular epithelial cells. To investigate the mechanisms of Cd-induced renal toxicity, we examined the effects of Cd on the ubiquitin-proteasome system, particularly the expression and function of Ube2d family members in the NRK-52E cells and mice. Cd markedly decreased the expression of Ube2d1, Ube2d2, Ube2d3 and Ube2d4 prior to the appearance of cytotoxicity in the NRK-52E cells. Cd also dramatically increased p53 protein levels in the cells, without stimulation of p53 gene expression or inhibition of proteasome activity. In addition, Cd induced phosphorylation of p53 and caused apoptosis in the NRK-52E cells. In vivo, we examined the effect of orally administrated Cd for 12 months on the expression of Ube2d genes and accumulation of p53 in the mouse kidney. Chronic Cd exposure also caused suppression of Ube2d genes expression and accumulation of p53. Cd did not induce severe kidney injury, but caused apoptosis in the renal tubules. These results suggest that the Cd-induced accumulation of p53 may be due to inhibition of p53 degradation through the down-regulation of Ube2d family genes, and that Cd induces p53-dependent apoptosis in renal tubular cells. Moreover, Ube2d family members may be one of the critical targets of renal toxicity caused by Cd.
    Full-text · Article · Apr 2011 · The Journal of Toxicological Sciences
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    ABSTRACT: Japanese flounder (Paralichthys olivaceus) were experimentally infected with the highly pathogenic scuticociliate Miamiensis avidus (syn. Philasterides dicentrarachi) using the immersion method to clarify/identify the possible neural routes of entry and possible ways of dissemination of the scuticociliate in the fish body. Scuticociliates were observed on the skin and gills right from day 0-1 post-infection, muscle tissue on day 2 post-infection, reached the brain, and spinal cord on day 3 post-infection, and systemic infection was prominent afterwards. Brain lesions were observed in most of the examined fish from days 3 and 4 post-infection and considered to be the cause of the sudden increase in mortality. Affected fish showed varying degrees of tissue damage including severe epidermal and dermal necrotic lesions, necrotic myositis, encephalitis and myelitis. Whereas, scuticociliates were frequently observed along the optic and/or olfactory nerve in the fish which were accompanied by severe brain lesions but by minimum lesions in the gills and skin, suggesting that in addition to skin and/or gills, neural routes including periorbital and nasal routes may play a role in scuticociliate invasion to the brain. Scuticociliates were also observed in the peripheral nerve fibers in the muscle tissue, cranial and spinal nerves, cranial cavity and in the vertebral canal, suggesting that nerve fibers and/or cerebrospinal fluid circulation may be involved in the spread of the scuticociliate throughout the body in addition to the blood circulation and connective tissue.
    No preview · Article · Dec 2010 · Journal of Veterinary Medical Science

Publication Stats

2k Citations
286.39 Total Impact Points

Institutions

  • 2013-2014
    • Azabu University
      • Laboratory of Pathology
      Sagamihara, Kanagawa, Japan
  • 1992-2013
    • Tottori University
      • Faculty of Agriculture
      TTJ, Tottori, Japan
  • 2007
    • National Institute for Environmental Studies
      • Center for Environmental Health Sciences
      Tsukuba, Ibaraki, Japan