Biomedical subjects

Jyoji Yamate

Publications and source records attributed to Jyoji Yamate.

At least 19 recordsLinked to original sources

PubMed2026

Disrupted development of the retina in the Ccdc85c knockout rat.

The coiled-coil domain-containing 85c (Ccdc85c) knockout (KO) rat generated by genome editing exhibits hydrocephalus and subcortical heterotopia. In this study, we aimed to further investigate the function of CCDC85C protein in the development of the retina. Expression of CCDC85C, acetylated tubulin, ciliary rootlet coiled-coil protein (CROCC), zonula occludens-1 (ZO-1), glutamine synthetase, and PAX6 were examined immunohistochemically in wild-type F344 rats at embryonic day (ED) 19 and at postnatal days (PNDs) 0, 4, 6, 13, and 20. Immunoelectron microscopy was performed for CCDC85C in the normal rat retina. Retinal lesions in Ccdc85c KO rats were examined using fundus photography, optical coherence tomography (OCT), and histology. In the normal rat retina, CCDC85C was co-localized with ZO-1 in the outer limiting membrane and persistently expressed after ED19. Ultrastructurally, CCDC85C was located between the outer nuclear layer and the inner segments, and showed the same location as the tight junction. In Ccdc85c KO rats, multifocal retinal dysplasia; disarrangement of the inner and outer segments, cilia, and rootlets; and impaired development of Müller cells were observed. In OCT images, Ccdc85c KO rats showed parallel hyperintense striations in the inner nuclear layer, and low reflectivity of the outer limiting membrane and layer of rods and cones. These results suggest that CCDC85C protein is located in the tight junction complex and is involved in retinal layer formation. The Ccdc85c KO rat model provides a novel tool to study retinal development as well as genetic hydrocephalus.

Ccdc85c↗

PubMed2006

Growth of benign and malignant schwannoma xenografts in severe combined immunodeficiency mice.

OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

Animals↗

PubMed2006

Systemic candidiasis in a dog, developing spondylitis.

A 4-year-old male Shiba dog initially presented with pain of an undetermined origin and hypersensitivity to touch. Seven days later, the dog developed ataxia, hind-leg weakness and knuckling. The dog died on 20 days after presentation. Postmortem examination revealed a mass in the body of thoracic vertebra. Histopathologically, the mass consisted of granulomatous inflammation, including fungal organisms that were immunohistochemically positive for Candida albicans. Similar granulomatous lesions were observed in the systemic lymph nodes, kidneys, pancreas, spleen, prostate gland, thyroid glands and heart. This case was diagnosed as systemic candidiasis with spondylitis.

Animals↗

PubMed2006

Expression patterns of the slit subfamily mRNA in canine malignant mammary tumors.

Slit, a secreted protein, functions as a chemorepellent factor in axon guidance and neuronal migration and as an inhibitor in leukocyte chemotaxis. In humans, slit2 protein attracts endothelial cells and promotes tube formation in the tumor angiogenic mechanism. In this study, we cloned a part of the canine slit subfamily and examined the expression of slit subfamily mRNAs in 3 normal canine mammary glands and 11 mammary tumor samples by RT-PCR. The cloned part of the slit gene sequences showed high similarity to those of the human, mouse, and rat. The mRNAs were expressed at low levels in the normal mammary gland. The expression levels of slit1 mRNA were low in both the normal and tumor tissues. In contrast, the expression of slit2 mRNA increased in most of the malignant mammary tumors, and an increase in slit3 mRNA expression was observed in 2 of the malignant mixed tumors. These results suggest that the expression of slit2 plays an important role in tumor angiogenesis in canine mammary gland tumors and that slit2 can be a putative marker for malignancy diagnosis of these tumors.

Animals↗

PubMed2006

Olfactory neuroblastoma in a horse.

An 11-year-old thoroughbred gelding was euthanatized because of right nasal cavity tumor. The tumor consisted of round to oval cells with a scanty cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes, as well as microcysts were seen. Neoplastic cells were immunoreactive to vimentin, S-100 protein, and neuron-specific enolase, glial fibrillary acidic protein and microtube-associated protein in varying degrees, indicating neurogenic nature. Based on these findings, this tumor was diagnosed as an olfactory neuroblastoma. Since this type is an uncommon tumor showing histological variety, the nature is discussed.

Animals↗

PubMed2006

Synovial sarcoma of the tendon and tendon sheath in a dog.

A 19.5-year-old male mongrel dog developed a progressive lameness and swelling around the right carpus. A tumor (6 x 3 x 3 cm) was found in the caudal of distal antebrachium of the right forelimb, including tendons of the superficial digital flexor muscle and deep digital flexor muscle. No joint destruction was observed. The tumor consisted of round and spindle cells arranged in a compact sheet. There were occasional slit-like spaces or lumina, and areas rich in collagen fibers giving an appearance of tendon tissues. Neoplastic cells gave a positive immunoreaction to vimentin, but negative reactions to antibodies against S-100 protein, cytokeratin and myoglobin. Based on these findings, this tumor was diagnosed as a synovial sarcoma generating from the tendon and tendon sheath, which is very uncommon in dogs.

Animals↗

PubMed2005

Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys, and in kidney-related cell lines under fibrogenic stimuli.

Myofibroblasts play an important role in chronic renal interstitial fibrosis. However, the origin and developmental mechanisms remain to be elucidated. The myofibroblasts may express various cytoskeletons during the development. Immunoexpressions of vimentin, desmin and alpha-smooth muscle actin (alpha-SMA) were analyzed using experimentally (cisplatin and unilateral ureteral obstruction) induced rat and spontaneous canine fibrotic kidneys or kidney-related cell lines incubated with transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor-BB (PDGF-BB) or their combination at various concentrations. In rat fibrotic kidneys, both renal epithelia and interstitial cells showed positive reactions to alpha-SMA and vimentin, supporting epithelial-mesenchymal transition (EMT) theory; however, renal epithelia did not react to desmin, though interstitial cells were reactive. Renal epithelia in canine fibrotic kidneys did not show a positive reaction to alpha-SMA, whereas interstitial cells reacted strongly to alpha-SMA; conversely, renal epithelia reacted strongly to desmin, but interstitial cells did not; vimentin expression was infrequently seen in renal epithelia and interstitial cells of canine kidneys. Exposure of TGF-beta1 to porcine renal epithelial cells (LLC-PK1), rat renal interstitial cells (NRK-49F), and rat immature mesenchymal cells (MT-9) dose-dependently increased selectively alpha-SMA-positive cell numbers. Moreover, PDGF-BB exhibited an additive effect on TGF-beta1-induced alpha-SMA expression in these cell lines when simultaneously added. alpha-SMA was the most plastic cytoskeleton under fibrogenic stimuli. This study shows that there are interspecies differences in cytoskeletal immunoexpressions of renal epithelia or interstitial cells between rat and canine fibrotic kidneys, and that the derivation of renal myofibroblasts may be heterogeneous, such as renal epithelia, interstitial cells or immature mesenchymal cells.

Actins↗

PubMed2005

Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats.

The present study was designed to characterize the nephrotoxicity induced by the antineoplastic platinum complex nedaplatin (NDP) in rats of different ages in comparison with cisplatin (CDDP). A single dose of 15 mg/kg NDP or 7.5 mg/kg CDDP was administered intravenously to 8-, 11-, or 15-week-old male and female SD rats, which were then sacrificed after ten days. Body weight decreases were observed for both drugs, in direct relation to age. CDDP treatment markedly increased urinary excretion of NAG, gamma-GTP, LDH and protein, with peaks on day 4 and complete or partial recovery on day 7; NDP increased NAG, LDH and protein excretion, but to a lesser extent, and these elevations were generally more marked for females. CDDP increased plasma creatinine and BUN in males and females of all age groups at necropsy. No apparent changes were seen following NDP treatment except in the 15-week-old rats. These results also show that NDP is less nephrotoxic than CDDP. CDDP-treated rats showed remarkable proximal tubular lesions in the renal cortex and corticomedullary region, and the papillary lesions were minor. On the other hand, the NDP-induced nephrotoxicity was morphologically characterized by hyaline droplet changes (electron microscopically, hyperplasia of lysosomes), necrosis or hyperplasia of the collecting duct epithelium in the renal papilla and the epithelium covering the papilla. Cortical lesions, indicated by slight tubular dilatation, were found only in the animals with papillary lesions. In summary, NDP is a promising second-generation platinum complex with reduced nephrotoxicity.

Animals↗

PubMed2005

Mutation at the Lmx1a locus provokes aberrant brain development in the rat.

A rat short-tail mutation with neurological defects (named queue courte, qc) was discovered. Histopathology in adult qc/qc rats revealed hypoplasia of the cerebellum and hippocampus, maldevelopment of the choroid plexus and corpus callosum. These abnormalities are strongly reminiscent of the phenotypic abnormalities found in the shaker short-tail or dreher (dr) mouse mutation at the LIM homeobox transcription factor 1 alpha locus (Lmx1a). The qc mutation is an autosomal recessive and has been mapped to the dr homologous region on rat chromosome 13, and Northern blot analysis demonstrated no expression of Lmx1a in qc/qc rats. Narrowing and distortion of the ventricles were observed from embryonic day 17 (E17) in qc/qc rats. From E17, fusion of the opposing neuroepithelium and formation of neuroepithelial rosettes were also found. Arrangements of neuroepithelial cells were disturbed and processes of radial glia were disoriented in the fused lesions. Neuronal migration analysis using BrdU immunohistochemistry revealed defective migration from the neuroepithelium toward the neocortex and mesencephalon in qc/qc rats. These findings suggest that the qc mutation is involved in development of the ventricular system and dorsal migration of neurons.

Animals↗

PubMed2005

Protective effect of polyphenol-containing azuki bean (Vigna angularis) seed coats on the renal cortex in streptozotocin-induced diabetic rats.

This study was undertaken to investigate the effect of azuki bean (Vigna angularis) seed coats (ABSC), which contain polyphenols, on the infiltration of macrophages and the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. The diabetic rats were divided into three groups with 0% (commercial diet), 0.1% and 1.0% ABSC diets. The vehicle-injected controls were given a commercial diet. At 10 weeks, the macrophage kinetics, the degree of fibrosis in glomeruli and mRNA expression for monocyte chemoattractant protein-1 (MCP-1) were examined. There was no difference in plasma glucose levels between diabetic rats treated with and without ABSC. The plasma levels of malondialdehyde (MDA) in the ABSC-treated diabetic rats were significantly lower than those in the untreated diabetic rats. Histopathologically, the percentage of the fibrotic areas stained by Sirius red stain in the glomeruli in the ABSC-treated diabetic rats was lower than in the untreated diabetic rats. ED1-positive macrophages in the glomeruli and tubulointerstitium in the untreated diabetic rats showed a significant increase in number compared with the controls. In contrast, the number of macrophages in the ABSC-treated diabetic rats was smaller than that in untreated diabetic rats. MCP-1 mRNA expression, estimated by real-time quantitative RT-PCR, was increased 2.5-fold in the untreated diabetic rat kidney, while a lower level was observed in the ABSC-treated diabetic rats. In conclusion, our results suggest that ABSC treatments suppress the increased number of infiltrating macrophages and MCP-1 mRNA expression, and attenuated the glomerular expansion in STZ-induced rat diabetic nephropathy.

Animals↗

PubMed2005

Protective effect of dietary azuki bean (Vigna angularis) seed coats against renal interstitial fibrosis of rats induced by cisplatin.

OBJECTIVE: We investigated the effects of azuki bean (Vigna angularis) seed coats (ABSCs), which mainly contain proanthocyanidins and dietary fibers, on the infiltration of macrophages and the progression of renal interstitial fibrosis induced by cisplatin (CDDP). METHODS: Male rats were divided into two groups: controls received intraperitoneal injections of saline and the other rats were injected intraperitoneally with 3 mg of CDDP per kilogram once a week for 5 wk. The CDDP-injected animals received one of four diets: 1) control diet (commercial diet only), 2) 0.5% red ABSC (RABSC) diet, 3) 2.0% RABSC diet, and 4) 2.0% white ABSC (WABSC) diet. The saline-injected animals were given the commercial diet. Five weeks after the final CDDP injection, macrophage kinetics and interstitial fibrotic areas were examined. RESULTS: The content of polyphenols in the RABSC (76.3 g/kg of plant material) was higher than that in the WABSC (18.1 g/kg). Proanthocyanidins were detected in the RABSC (20.4 g/kg) but not in the WABSC. Histologically, the fibrotic areas consisting of fibroblastic cells and mononuclear cells developed around the dilated or atrophic tubules in the corticomedullary junction in CDDP-treated rat kidney, whereas the extent and magnitude of damage were less in the WABSC- and RABSC-treated rats. In immunohistochemical analysis, ED1-positive macrophages in CDDP-treated rats showed a significant increase in number compared with the control. The number of macrophages in CDDP plus WABSC or RABSC groups was significantly smaller than that in CDDP-treated rats. In addition, the number of macrophages in the RABSC group was significantly smaller than in the WABSC group, indicating that ABSC, especially RABSC, prevented macrophages from infiltrating into areas of interstitial fibrosis. CONCLUSIONS: These results suggest that ABSC, especially RABSC, suppress the increase of infiltrating macrophages in the damaged kidney and may lead to amelioration of interstitial fibrosis. Based on the composition of ABSC, molecules such as proanthocyanidins and/or dietary fibers may be associated with the amelioration of renal damage.

Animals↗

PubMed2005

Cisplatin-induced renal interstitial fibrosis in neonatal rats, developing as solitary nephron unit lesions.

Cisplatin (CDDP)-induced renal lesions in rats prove a useful model for analysis of the pathogenesis of post-tubular injury-renal interstitial fibrosis. This study investigated the histopathological changes in 10-day-old neonatal rats induced by a single injection of CDDP (4.5 mg/kg). Compared with age-matched controls, on postinjection (PI) days 1 to 6, the number of apoptotic cells, demonstrable with TUNEL method, was significantly increased in CDDP-treated neonates, and there was no marked epithelial necrosis nor fibrotic lesions. Fibrotic lesions began to be developed solitarily around some nephrons with dilated ducts in the corticomedullary junction on PI day 10 and the lesions became more prominent until PI day 20. The alpha-SMA-positive myofibroblastic cells were seen exclusively in the fibrotic lesions. Additionally, the numbers of macrophages reacting with EDI (specific for exudate macrophages), ED2 (for resident macrophages), and OX6 (recognizing MHC class II antigens expressed in antigen-presenting macrophages/dendritic cells) were significantly increased around the affected renal tubules. A greater immunoreaction for TGF-beta1 was seen mostly in the renal epithelial cells of CDDP-treated neonates. These findings indicated that macrophage populations and myofibrolastic cells as well as TGF-beta1 may be responsible for the production of neonatal renal interstitial fibrosis. Compared with CDDP-injected adult rats that develop extensive interstitial fibrosis (Yamate et al., J Comp Pathol, 1995), the formation of fibrotic lesions was delayed, and the lesions were limited to the area around the affected nephrons; this could be attributable to differences in renal morphology between neonates and mature kidney of adult rats.

Actins↗

PubMed2005

Gastric adenocarcinoma with ossification in a ferret (Mustela putorius furo).

A 6-year-old female ferret had a firm mass 2 cm in diameter in the pyloric region of the stomach. Histopathologically, the mass was composed of neoplastic proliferation of well-differentiated epithelial cells, showing tubular or glandular growth patterns. Osseous metaplastic foci were often found in the tumor. Tumor cells showed a positive reaction for immunohistochemistry against bone morphogenetic protein-6, an osteogenic factor. A diagnosis of gastric adenocarcinoma with ossification was made.

Adenocarcinoma↗

PubMed2004

Immunohistochemical and morphometrical studies on myelin breakdown in the demyelination (dmy) mutant rat.

The demyelination (dmy) rat is a unique mutant exhibiting severe myelin breakdown in the central nervous system (CNS). In this study, we conducted immunohistochemical and morphometrical investigations in the dmy rat. From around 6 weeks of age, the affected rats developed ataxia especially in the hindlimbs. Afterwards, ataxia worsened rapidly, resulting in complete paralysis of the hindlimbs and recumbency. Histopathology at 7 to 10 weeks of age revealed myelin destruction throughout the white matter of the CNS in the dmy rats. The most severely affected lesions were distributed in the corpus callosum, capsula interna, striatum, subcortical white matter, cerebellar peduncle, and ventral and lateral parts of the spinal cord. Immunohistochemistry demonstrated prominent astrogliosis and many ED-1 positive macrophages in the myelin-destructed areas. Until the 4th week, no significant differences in myelin thickness and fiber diameter were found between dmy and control rats. However, from 5 weeks of age, myelin thickness of residual myelinated fibers in dmy rats became significantly less than that in controls. These data indicated that the dmy phenotype shows a prolonged period of myelin destruction, suggesting that dmy mutation affects the adequate maintenance of myelin.

Age Factors↗

PubMed2004

Hemorrhagic hydrocephalus (hhy): a novel mutation on mouse chromosome 12.

A novel mouse hemorrhagic hydrocephalus mutation (hhy) inherited in an autosomal recessive manner on chromosome 12 has been found at the Osaka Prefecture University. The hhy homozygous mutant had dilated lateral ventricles and a communicating aqueduct, with no histological abnormalities either in the subarachnoid space or in the choroid plexus. Multiple hemorrhages in the meninges and throughout the brain parenchyma of the mutant were relevant to advanced stages of hydrocephalus. Subcortical heterotopia was detected unexceptionally in the mutants. Thus, the hhy mutation is characterized by three different abnormalities, i.e. hydrocephalus, intracranial hemorrhage and subcortical heterotopia.

Animals↗

PubMed2004

Effects of lipopolysaccharide on the appearance of macrophage populations and fibrogenesis in cisplatin-induced rat renal injury.

Macrophages play an important role in renal interstitial fibrosis via production of transforming growth factor-beta1 (TGF-beta1) and tumor necrosis factor-alpha (TNF-alpha); these fibrogenic factors mediate induction of myofibroblastic cells capable of producing extracellular matrices. We investigated the effects of lipopolysaccharide (LPS), a macrophage activator, on the appearance of macrophage populations and subsequent fibrogenesis in cisplatin (CDDP)-induced rat renal lesions. In keeping with the progression of interstitial fibrosis, alpha-smooth muscle actin (alpha-SMA)-immunopositive myofibroblastic cell number began to increase on day 4 and continued gradually until day 16 after CDDP injection. Cells immunoreactive for ED1 (for exudate macrophages), ED2 (for resident macrophages) and ED3 (for activated resident macrophages) showed the highest number on day 4 or day 7, and thereafter, the numbers were gradually decreased up to day 16. On the other hand, the number of cells immunoreactive for OX6 (rat MHC class II-recognizing antibody) was increased on day 7 and remained elevated up to day 16. LPS was injected on day 7 after CDDP injection when the greatest number of ED1-positive macrophages were present. In CDDP/LPS-injected rats, the numbers of macrophages reacting to ED1, ED2, ED3, and OX6 were higher than those in CDDP-injected rats during the observation period between days 7 and 16; ED3- and OX6-positive cells were more prominently increased than ED1- and ED2-postive cells. By RT-PCR analysis, the expression of TGF-beta1 and TNF-alpha mRNAs in CDDP/LPS-injected rats on day 7 was markedly increased in contrast to those in CDDP-injected rats. These findings indicate that LPS treatment enhanced the macrophage expression of fibrogenic factors. However, there was no marked difference in the fibrogenesis between CDDP/LPS- and CDDP-injected rats. These findings suggest that the macrophage populations appearing in CDDP-induced rat renal lesions should be investigated further, to address the complicated pathogenesis of renal interstitial fibrosis.

Animals↗

PubMed2004

Distributive and phagocytic characteristics of hepatic macrophages in five cetaceans belonging to Delphinidae and Ziphiidae.

Details of morphology and distribution of hepatic macrophages in cetaceans were investigated using the immunohistochemistry with an antibody (SRA-E5) generated against human macrophage scavenger receptor antigen. Liver samples were obtained from five species of cetaceans (Baird's beaked whales, short-finned pilot whales, Risso's dolphins, bottlenose dolphins, and pantropical spotted dolphins). Except for two species of whales, the number of SRA-E5-positive Kupffer cells was greatest in the perivenous zone (zone 3), followed by the mid-zonal (zone 2) and periportal (zone 1) zones; this distribution pattern was different from that in cattle examined here and previously reported rodents with the highest number in zone 1. The frequency of Kupffer cell in each of zones was significantly different among species, and interestingly, the total mean of the Kupffer cell number in three zones increased as the body-length of species was small. In cetaceans, Kupffer cells in zone 1 appeared larger and more stellate in shape, whereas those in zone 3 were smaller and rounder. All cetaceans but Baird's beaked whales had the black pigment-containing Kupffer cells, with the greatest number in zone 3, and macrophages with the similar pigments were also seen in the hepatic intermediate septa, indicating an active phagocytosis. Most of the black pigments were considered to be lipofuscin and such pigments were not seen in the bovine livers. These results indicate that cetacean hepatic macrophages show differences in the distribution and phagocytosis among hepatic lobular zones, or between cetacean species and terrestrial animals.

Animals↗

PubMed2004

Rat mutations cvd and hob with cerebellar malformations map to chromosome 2.

In this paper, we executed genome mapping and comparative mapping analyses for cvd and hob, autosomal recessive mutations with cerebellar vermis defect and cerebellar dysplasia in the rat. For the linkage analysis, we produced three sets of backcross progeny, (ACI x CVD)F(1) and (F344 x CVD)F(1) females crossed to a cvd homozygous male rat, and (HOB x WKY)F(1) males crossed to hob homozygous female rats. Analysis of the segregation patterns of simple sequence length polymorphism (SSLP) markers scanning the whole rat genome allowed the mapping of these autosomal recessive mutations to rat Chromosome (Chr) 2. The most likely gene order is D2Mgh12 - D2Rat86 - D2Mit15 - D2Rat185 - cvd - D2Rat66 - D2Mgh13, and D2Mit18 - Fga -D2Mit14 - D2Rat16 - hob - D2Mgh13. Crossing test between a proven cvd heterozygous and a hob heterozygous rats demonstrated their allelism. Furthermore, comparative mapping indicated the cvd locus corresponds to mouse chromosome 3 and a strong candidate gene Unc5h3, a causative gene for the rostral cerebellar malformation mouse, was implicated.

Alleles↗