[Anti-reticulin antibody].
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Autoantibodies↗
Biomedical subjects
Y Tajima
Publications and source records attributed to Y Tajima.
Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line.
Stroke mortality has declined over recent decades, prompting a demand for the development of effective rehabilitative therapies for stroke survivors. This effort has been facilitated by significant progress in replicating the behavioral and neuropathological changes of authentic human cerebral ischemia using relevant animal models. Since the rodent model of middle cerebral artery occlusion mimics several motor abnormalities seen in clinical cerebral ischemia, we have utilized this model to investigate treatment strategies for stroke. The present study explored the potential benefits of neural transplantation of fetal rat striatal cells or human neurons derived from a clonal embryonal carcinoma cell line to correct the abnormalities associated with cerebral ischemia. We report here that ischemia-induced behavioral dysfunctions were ameliorated by the neural grafts as early as 1 month post-transplantation. Of note, transplantation of human neurons induced a significantly more robust recovery than fetal rat striatal grafts. Thus, the logistical and ethical concerns about the use of fetal striatal cells for transplantation therapy can be eliminated by exploiting cell line-derived human neurons as alternative graft sources. Transplantation of human neurons has a therapeutic potential for treatment of behavioral deficits associated with cerebral ischemia.
Animals↗
Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases.
BACKGROUND: Malignant myoepithelioma (MME) of the salivary gland, also known as myoepithelial carcinoma, is rare and its biologic behavior has not been clarified fully. METHODS: Ten cases of MME were analyzed for their clinicopathologic features and immunohistochemical characteristics, focusing on prognostic factors and tumor differentiation. In addition, six cases of benign myoepithelioma (BME) also were examined for comparison. RESULTS: The ten patients with MME (3 men and 7 women) ranged in age from 48-81 years (mean, 61.9 years). Seven cases of MME arose in the parotid salivary gland, two in the submandibular salivary gland, and one in minor salivary glands of the soft palate. In the current series, the incidence of MME was 0.45% among 1945 cases of major salivary gland tumors. Seven cases of MME developed from a benign preexisting tumor (six in pleomorphic adenoma and one in BME). Four of nine patients with MME died of the disease and two patients developed a recurrence. It was shown that MMEs were comprised of one cell type or a combination of two cell populations; these included, in order of incidence, epithelioid, spindle, and plasmacytoid cells. Patients with MME with marked cellular pleomorphism and perineural invasion had a poor prognosis. Immunohistochemically, putative myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, and calponin, and S-100 protein were expressed highly in MME. High and low molecular weight cytokeratins and epithelial membrane antigen also frequently were positive in MME. p53 expression was observed in five MME cases, four of which either recurred or were fatal. Cellular proliferative activity assessed by mitotic count and the Ki-67 labeling index was significantly higher in MME cases than in BME cases. In limited cases, such cellular proliferative activity was shown to have prognostic value. Ultrastructurally, the tumor cells displayed certain myoepithelial characteristics. CONCLUSIONS: MME is a rare salivary gland tumor showing clinicopathologic diversity and presenting with various stages of myoepithelial differentiation. Histologic aggressiveness, marked cellular pleomorphism, p53 expression, and high cell proliferative activity were found to be correlated with a poor clinical outcome.
Actins↗
Consequences of exclusive expression in vivo of Kit-ligand lacking the major proteolytic cleavage site.
Membrane growth factors that are processed to produce soluble ligands may function both as soluble factors and as membrane factors. The membrane growth factor Kit-ligand (KL), the ligand of the Kit receptor tyrosine kinase, is encoded at the Sl locus, and mice carrying Sl mutations have defects in hematopoiesis, gametogenesis, and melanogenesis. Two alternatively spliced KL transcripts encode two cell-associated KL protein products, KL-1 and KL-2. The KL-2 protein lacks the major proteolytic cleavage site for the generation of soluble KL, thus representing a more stable cell-associated form of KL. We investigated the consequences of exclusive expression of KL-2 in vivo. The KL gene in embryonic stem cells was modified and KL exon 6 was replaced with a PGKneoNTRtkpA cassette by homologous recombination, and mice carrying the SlKL2 allele were obtained. SlKL2/SlKL2 mice had only slightly reduced levels of soluble KL in their serum, suggesting that in vivo KL-2 may be processed to produce soluble KL-2S. The steady-state characteristics of the hematopoietic system and progenitor numbers were normal, and the mutant animals were not anemic. However, mast cell numbers in the skin and peritoneum were reduced and the mutant animals displayed increased sensitivity to sublethal doses of gamma-irradiation. Therefore, KL-2 may substitute for KL-1 in most situations with the exception of the production of mast cells, and induced proteolytic cleavage of KL-1 to produce soluble KL may have a role in the regeneration of hematopoietic tissue after radiation injury.
Alternative Splicing↗
Role of dimerization of the membrane-associated growth factor kit ligand in juxtacrine signaling: the Sl17H mutation affects dimerization and stability-phenotypes in hematopoiesis.
The Kit ligand (KL)/Kit receptor pair functions in hematopoiesis, gametogenesis, and melanogenesis. KL is encoded at the murine steel (Sl) locus and encodes a membrane growth factor which may be proteolytically processed to produce soluble KL. The membrane-associated form of KL is critical in mediating Kit function in vivo. Evidence for a role of cytoplasmic domain sequences of KL comes from the Sl17H mutation, a splice site mutation that replaces the cytoplasmic domain with extraneous amino acids. Using deletion mutants and the Sl17H allele, we have investigated the role of the cytoplasmic domain sequences of KL in biosynthetic processing and cell surface presentation. The normal KL protein products are processed for cell surface expression, where they form dimers. Both Sl17H and the cytoplasmic deletion mutants of KL were processed to the cell surface; however, the rate of transport and protein stability were affected by the mutations. Deletion of cytoplasmic domain sequences of KL did not affect dimerization of KL. In contrast, dimerization of the Sl17H protein was reduced substantially. In addition, we have characterized the hematopoietic cell compartment in Sl17H mutant mice. The Sl17H mutation has only minor effects on hematopoiesis. Tissue and peritoneal mast cell numbers were reduced in mutant mice as well as in myeloid progenitors. Interestingly, long-term bone marrow cultures from Sl17H mice did not sustain the long-term production of hematopoietic cells. In addition, homing of normal hematopoietic progenitors to the spleen of irradiated Sl17H/Sl17H recipient mice was diminished in transplantation experiments, providing evidence for a role of Kit in homing or lodging. These results demonstrate that the membrane forms of KL exist as homodimers on the cell surface and that dimerization may play an important role in KL/Kit-mediated juxtacrine signaling.
Amino Acid Sequence↗
Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats.
This study was designed to explore the efficacy of a human clone cell line as an alternative neural graft source and to validate the practice of cryopreservation and xenografting as logistical approaches toward conducting neural transplantation. We investigated the biological effects of transplanting cultured human neurons (NT2N cells) derived from a well-characterized embryonal carcinoma cell line into the brains of rats subjected to transient, focal cerebral ischemia induced by embolic occlusion of the middle cerebral artery. At 1 month and extending throughout the 6-month posttransplantation test period, ischemic animals that were transplanted with NT2N cells and treated with an immunosuppressive drug displayed a significant improvement in a passive avoidance task as well as a normalization of asymmetrical motor behavior compared to ischemic animals that received rat fetal cerebellar cell grafts or vehicle alone. Remarkably, cryopreserved NT2N cell grafts compared with fresh NT2N cell grafts, remained viable in the immunosuppressed rat brain and effective in producing behavioral recovery in immunosuppressed ischemic animals. The long-term viability of cryopreserved NT2N cell xenografts in vivo and their sustained effectiveness in promoting behavioral recovery suggest potential utilization of xenografting and cryopreservation as useful protocols for establishing clone cell lines as graft source in neural transplantation therapies for central nervous system disorders.
Animals↗
Neurotrophins and neuronal versus glial differentiation in medulloblastomas and other pediatric brain tumors.
Medulloblastomas are highly malignant and poorly understood childhood neoplasms. To determine if neurotrophins might influence the phenotypic properties of medulloblastoma in a paracrine or autocrine manner, 51 pediatric brain tumors including 20 biopsy specimens of these primitive neuroectodermal tumors (PNETs) and 31 other pediatric brain tumors were studied. Immunohistochemistry was used with antibodies to nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3, their cognate high affinity receptors as well as to neuronal and glial markers. TrkA, TrkB, and TrkC were observed in 5 (25%), 8 (40%), and 17 (85%), respectively, of these medulloblastomas while NGF, BDNF, and NT-3 were observed in 6 (30%), 8 (40%), and 3 (15%), respectively, and antibodies to neurofilament (NF) and glial fibrillary acidic proteins (GFAP) stained 16 (80%) and 11 (55%), respectively. TrkA and NGF were not observed in the same biopsy samples, while TrkB and BDNF were co-distributed in 6 of the cases, all of which expressed NF proteins. TrkC and NT-3 were co-distributed in 3 of the medulloblastomas, and these areas overlapped with NF protein-positive tumor cells in all 3 cases. In contrast to medulloblastomas, TrkA and NGF co-distributed in other pediatric brain tumors, and both Trk receptors and their neurotrophins co-distributed with GFAP-positive tumor cells in 13 (42%) of the non-PNET pediatric brain tumors. The absence of medulloblastomas that contain NGF and TrkA is consistent with in vitro data demonstrating that NGF-mediated TrkA signaling induces apoptosis. Finally, this study also suggests that BDNF and NT-3 may act in a paracrine or autocrine manner through TrkB and TrkC receptors, respectively, to induce neuronal differentiation in medulloblastomas.
Adolescent↗
Small non-functioning endocrine tumor of pancreas: comparison with solid cystic tumor.
A small non-functioning islet-cell tumor of the pancreas in a 79-year-old man is reported. Ultrasonography showed a solid small mass in the body of the pancreas. All laboratory data, including serum hormones and tumor markers, were within normal limits. A distal pancreatectomy was performed. Cut sections of the specimen revealed a small, hard, solid mass measuring 2.8 x 2.2 x 2.0 cm. Histologically, the tumor consisted of large acidophilic cells with round nuclei, and these cells were similar to those normally found in solid and cystic tumors (SCT) of the pancreas. However, the tumor cells were slightly positive for somatostatin and neuron-specific enolase. Ultrastructural studies revealed clear nuclei with no zymogen but immature neurosecretory granules in the cytoplasm of the tumor cells. These findings were consistent with those of non-functioning islet-cell tumors. We describe the clinical and histological differences between non-functioning islet-cell tumors and SCT based on an analysis of the literature.
Adenoma, Islet Cell↗
Immunohistochemical profile of basic fibroblast growth factor and heparan sulphate in adult rat mandibular condylar cartilage.
Basic fibroblast growth factor (bFGF) and heparan sulphate (HS) were detected immunohistochemically in mandibular condylar cartilage, and the findings compared with those on epiphyseal articular cartilage. In the condylar cartilage, both bFGF and HS were localized in chondrocytes throughout the various zones including the fibrous, proliferative, mature-cell and hypertrophic zones: bFGF immunostaining was most significant in the proliferative and mature-cell zones, while intense staining for HS was found mainly in the hypertrophic zone. Immunoreaction for bFGF was detected in the nuclei of chondrocytes, whereas HS staining was observed in the cytoplasm. In articular cartilage, only chondrocytes beneath the superficial zone (intermediate zone) demonstrated both bFGF and HS immunoreactivities. Chondrocytes in the deeper calcifying region of the articular cartilage did not immunoreact for either bFGF or HS. These findings suggest that, in contrast to the epiphyseal articular cartilage, a continuous bFGF-mediated remodelling of cells and matrix takes place in mandibular condylar cartilage during the process of endochondral ossification.
Animals↗
The effects of estrogen deficiency on glycosylation of odontoblasts in rats.
To investigate the effects of estrogen deficiency on odontoblast metabolism, we induced osteoporosis in rats by ovariectomy and examined the glycosylation of the matrix component in odontoblasts. Peanut agglutinin (PNA) lectin histochemistry, which detects D-galactose and N-acetylgalactosamine sugars, was conducted in incisor odontoblasts of ovariectomized (OVX) and sham-operated (sham) rats. At 5 wk after the operation, bone mineral density and serum level of estrogen in OVX rats were lower than those in sham rats. PNA binding sites were found in the odontoblasts in incisors, and the binding sites in OVX rats were much stronger than those in sham rats. Furthermore, PNA binding sites were localized at the predentin matrix in OVX rats, but the reaction in sham rats was not detected. Because D-galactose and N-acetylgalactosamine sugars bound to PNA are important constituents of proteoglycans in dentin matrix and the PNA binding sites reflect the proteoglycan production of odontoblasts, these results indicated that galactosyl glycosylation of proteoglycans in odontoblasts is influenced by estrogen deficiency in rat incisors.
Acetylgalactosamine↗
Ovariectomy causes cell proliferation and matrix synthesis in the growth plate cartilage of the adult rat.
The in vivo effects of ovariectomy in rats have been studied on cell proliferation and matrix synthesis in the growth plate cartilage by assessing immunohistochemically the levels of proliferating cell nuclear antigen and chondroitin sulphate proteoglycan(s). The serum levels of insulin-like growth factor-I and growth hormone were also measured by radioimmunoassay procedures. At 5 weeks after ovariectomy, the serum levels of the growth factor were significantly higher than those in sham-operated rats. In contrast, the level of growth hormone was lower. The nuclear staining of proliferating cell nuclear antigen was generally seen in the zone of proliferative chondrocytes from both groups of rats. Whereas almost all chondrocytes in the proliferative zone of ovariectomized rats expressed proliferating cell nuclear antigen immunoreactivity, fewer did so in that of the sham rats. Quantitative image analysis by ACAS 570 laser cytometry demonstrated that the nuclear antigen-positive sites in ovariectomized rats had significantly higher integrated values (staining intensity), areas and perimeters than those in sham rats. In addition, the number of chondroitin sulphate proteoglycan-immunoreactive cells in the proliferative chondrocytes was also higher in ovariectomized rats than in sham ones. These results suggest that ovariectomy significantly stimulates the cell proliferation and matrix synthesis in the growth plate cartilage, probably through the higher serum level of insulin-like growth factor-I.
Animals↗
Mucoepidermoid carcinoma arising in Warthin's tumour of the parotid gland: report of two cases with histopathological, ultrastructural and immunohistochemical studies.
AIMS: Malignant transformation of Warthin's tumour (WT) is a rare event. We present two cases of mucoepidermoid carcinoma (MEC) arising in WT in the parotid gland. METHODS AND RESULTS: Two cases of MEC arising in WT, which were found in 185 cases of WT of the parotid gland, were investigated by light and electron microscopy, and immunohistochemistry. Both cases had largely similar macroscopic and histological features with some differences. Histologically, the tumours consisted mainly of WT with multilayered hyperplastic arrangements of oncocytic cells and focal squamous and goblet cell metaplasia. In the same tumour mass, however, the features of MEC were observed with invasion to adjacent adipose tissue. A transitional zone between WT and MEC was evident. Both patients were alive and well without evidence of recurrence 30 and 34 months after surgery, respectively. Electron microscopy revealed that cyst lining epithelial cells in WTs had abundant mitochondria whereas some of the MEC cells contained numerous tonofilaments and mucinous granules. Immunohistochemically, oncocytic cells of WTs were strongly positive for mitochondria and SalylTn was extensively stained in MECs. The labelling index for Ki67 was obviously higher in the carcinoma cells than the epithelial cells of WT. CONCLUSIONS: Our cases confirmed the possibility of malignant transformation of the epithelial component in WT to MEC.
Adenolymphoma↗
Comparison of proliferating cell nuclear antigen expression in odontogenic keratocyst and ameloblastoma: an immunohistochemical study.
Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S phase of the cell cycle, and immunohistochemical detection of the protein represents a useful marker for the proliferating fraction of cells in tissue specimens. PCNA expression was studied in odontogenic keratocysts (n = 15) and ameloblastomas (n = 46) using an avidin-biotin-peroxidase complex method on routinely processed paraffin sections. The percentage of PCNA-positive cells determined by point counting was significantly lower in the ameloblastomas (mean 9.4%, standard deviation (SD) 11.0) than in odontogenic keratocysts (mean 29.9%, SD 24.0). In ameloblastomas, the mean percentage of PCNA-positive cells was lowest in the acanthomatous pattern and highest in plexiform pattern. The mean percentage of PCNA-positive cells in plexiform pattern was non-significantly higher than that in follicular pattern. The mean percentage of PCNA-positive cells in plexiform and follicular patterns was significantly higher than that in cystic and acanthomatous patterns. The frequency of PCNA-positive cells was significantly higher in the peripheral cells of follicular and plexiform patterns than in the central cells of both patterns (p < 0.01). Therefore, peripheral cells were regarded as reserve cell of central cells. The mean percentage of PCNA-positive cells in the epithelial lining of odontogenic keratocyst was not significantly different from those in the peripheral cells of follicular and plexiform patterns of ameloblastoma. In contrast, the odontogenic keratocyst exhibited a mean percentage of PCNA-positive cells which was statistically higher than that in other histological elements of ameloblastomas. The present study suggests that odontogenic keratocyst is regarded as benign odontogenic tumour.
Ameloblastoma↗
Laparoscopic external drainage of a pancreatic pseudocyst associated with periportal collaterals.
A pseudocyst of the pancreas was detected in a 44-year-old man with alcoholic chronic pancreatitis. Ultrasound-guided puncture and drainage were attempted but were unsuccessful because of unexpected bleeding from the collateral veins around the cyst wall. Consequently, a laparoscopic puncture was performed and proved to be effective.
Adult↗
[Serial MRI, SPECT and 1H-MRS findings in a case of herpes simplex encephalitis].
We report herein a case of herpes simplex encephalitis (HSE) in which magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and proton magnetic resonance spectroscopy (1H-MRS) were performed sequentially. Both MRI and SPECT demonstrated a lesion on the left temporal lobe in its early stage. However, SPECT seemed more sensitive because it could detect subtle alterations of the blood flow. Hyperperfusion identified by SPECT had returned to normal levels while the abnormal MRI findings still remained. This may indicate that normalization of the blood perfusion precedes the tissue recovery. Contrast enhancement using Gd-DTPA was observed along the surface of the cerebral cortex on MRI, but that involved only part of the hyperperfusion areas depicted with SPECT. In the affected left temporal lobe, 1H-MRS exhibited reduction of N-acetyl-asparate (NAA), and an elevated lactate level. The former represented the neuronal loss, and the latter indicated impairment of oxidative metabolism. Furthermore, alterations of NAA/creatine (Cr) and choline (Cho)/Cr ratios were also observed in the seemingly normal right temporal lobe. Those ratios returned to nearly normal levels in accordance with the patient's clinical recovery. Subsequently, our results indicate that 1H-MRS might be a very useful tool in qualifying the tissue damage and possibly estimating the prognosis.
Encephalitis, Viral↗
Purification of a factor that enhances the antibacterial activity of beta-lactams against methicillin-resistant Staphylococcus aureus: its identification as undecaphosphotungstate.
Previously, a factor (Factor T) was found in aged mixtures of tungstate and phosphate, which greatly enhances the antibacterial effects of beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus. Factor T was purified and identified as undecaphosphotungstate ([PW11O39]7-). Undecasilicotungstate ([SiW11O39]8-), a compound closely related to undecaphosphotungstate, showed a similar enhancing effect.
Anti-Bacterial Agents↗
Cloning of human chromosome 17-specific cDNAs using representational difference analysis and human-mouse hybrid cells.
We employed cDNA representational difference analysis (RDA) with human-mouse somatic hybrid cells containing human chromosome 17 and obtained several cDNA clones specific for this chromosome. A cDNA library from PHA-stimulated T cells was screened with unknown cDNA clones obtained by RDA as probes. Subsequently, 1 complete gene and 1 partial cDNA clone were obtained. Our successful result implies that this subtractive amplification technique with hybrid cells will be a useful aid in positional cloning in large-spanning regions.
Amino Acid Sequence↗
K-ras gene mutations in intrahepatic bile duct tumors of Syrian golden hamsters.
BACKGROUND AND OBJECTIVES: In our laboratory, we have developed a new model of carcinoma of the bile duct in Syrian golden hamsters, using N-nitrosobis(2-oxopropyl)amine (BOP). Morphologic and biologic characteristics of the carcinoma induced in this model are similar to those seen in humans. In order to examine the gene-related carcinogenesis of intrahepatic bile duct carcinoma, we investigated mutations in the K-ras gene in various early hyperplastic and neoplastic lesions of these hamsters, according to the original sites of the lesions. METHODS: Inbred female hamsters were given a subcutaneous injection of N-nitrosobis(2-oxopropyl)amine (BOP) following dissection of the extrahepatic bile duct on the distal end of the common duct and preparation of a cholecystoduodenostomy (CDDB) or simple laparotomy (SL). Neoplastic lesions arising from the intrahepatic bile duct were histologically examined, and K-ras mutations were investigated. RESULTS: Mutations of K-ras codon 12 were evident in 12% of tubular hyperplasias, 19% of tubular adenocarcinomas, 15% of papillary hyperplasias and 36% of papillary adenocarcinomas. In papillary adenocarcinoma arising from a large bile duct, K-ras mutations occurred more frequently than in tubular adenocarcinoma arising from ductule or ductular proliferation. K-ras mutations were present even in a hyperplasia; the positive rates of the mutations increased in the presence of a carcinoma. Genetic changes in carcinoma of the intrahepatic bile duct varied based on sites of the duct and the histological type. CONCLUSIONS: A part of the hyperplastic lesions of the intrahepatic bile duct presented K-ras gene mutation. This suggests that K-ras gene mutation is an early event in the carcinogenic process. In carcinoma of the intrahepatic bile duct, the lesion arising from a large bile duct of the hepatic hilum tended to exhibit a higher frequency of K-ras gene mutation than did a tubular lesion arising from ductule or ductal proliferation. This hamster model is useful to examine the carcinogenesis of human intrahepatic bile duct carcinoma.
Adenocarcinoma↗