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At least 973 records · Page 54Linked to original sources
PubMed2005

Engraftment of freshly isolated or cultured human umbilical cord blood cells and the effect of cyclosporin A on the outcome.

Human umbilical cord blood (HUCB) is a potentially valuable resource for cell therapy. The present study investigated the short-term survival of intrastriatal grafts of either freshly isolated or cultured HUCB cells and the effect of the immunosuppressive agent cyclosporin A (CSA) in host rat brains. The group injected with either freshly isolated or cultured HUCB cells was subdivided into CSA or saline controls. Freshly isolated and cultured HUCB cells displayed surface markers CD33, CD44, CD45, CD51/61 and CD90/Thy-1. The hematopoietic progenitor marker CD34 was expressed only in freshly isolated cells. The majority of injected HUCB cells were localized within a 500-mum radius from the injection site in the striatum; however, a subpopulation migrated along the corpus callosum. There was no significant statistical difference in the cell count between freshly isolated and cultured HUCB cells with or without CSA. Some grafted HUCB cells expressed either a neural or microglial marker. There was weak up-regulation of major histocompatibility complex (MHC) class I antigen in rats either with or without CSA. However, there were considerably fewer positive cells labeled with an MHC class II antigen in CSA groups. These results suggest that neither freshly isolated nor cultured HUCB cells induce acute rejection after intrastriatal transplantation up to 14 days. CSA suppressed up-regulation of MHC class II antigen in the host brain.

Animals↗
PubMed2005

Ethyl-EPA treatment improves motor dysfunction, but not neurodegeneration in the YAC128 mouse model of Huntington disease.

Huntington disease (HD) is an adult-onset neurodegenerative disorder that is characterized by selective degeneration in the striatum. There are currently no treatments that can prevent the progressive decline of motor and cognitive function in HD. In parallel with a human clinical trial, we examined the efficacy of ethyl-EPA treatment in the YAC128 mouse model of HD. Oral delivery of ethyl-EPA to symptomatic YAC128 mice beginning at 7 months of age increased membrane EPA levels 3-fold (P < 0.001) and resulted in a modest but significant improvement in motor dysfunction by 12 months of age as measured by open-field activity (P = 0.01) and performance on the rotarod (P = 0.05). At this age, ethyl-EPA-treated YAC128 mice showed no improvement in striatal volume, striatal neuron counts, striatal neuronal cross-sectional area, or striatal DARPP-32 expression compared to untreated YAC128 mice, thereby indicating no reduction of striatal neuropathology. This result is congruent with modest motor benefits observed in HD patients treated with ethyl-EPA. Overall, this work demonstrates the feasibility of experimental therapeutics in the YAC128 mouse model and suggests that experiments in these mice may be predictive for future human clinical trials.

Animals↗
PubMed2006

Differential neurogenic potential of progenitor cells in dentate gyrus and CA1 sector of the postischemic adult monkey hippocampus.

The adult mammalian hippocampus contains neural progenitor cells capable of neuronal production under normal conditions. Cerebral injuries such as ischemia lead to their upregulation in rodent models, resulting in neurogenesis in the dentate gyrus (DG) and CA1 sector. The adult primate DG also has neurogenic potential under normal conditions, and we have previously shown that transient global cerebral ischemia increases progenitor cell proliferation in monkey DG, with a peak in the second postischemic week. Until now, however, long-term effects of ischemia on adult-generated cells in the primate hippocampus have not been described. We show here that nearly 15% of the adult-generated cells in monkey DG express neuronal features in the dentate granule layer for at least 79 days after the insult. At the same time, most adult-born cells in DG sustained their localization in the subgranular zone with an immature progenitor phenotype. In contrast to DG, no signs of neuronal production were observed in the postischemic hippocampus proper and in particular in the CA1 sector, where the newly-born cells were consistently of glial phenotype. Proliferating progenitors in DG but not in the subventricular zone adjacent to CA1 expressed the pro-neural transcription factors Emx2, Pax6 and Ngn2. Taken together, these results suggest that the neuronal production in adult monkey hippocampus after global brain ischemia is limited to DG and does not occur in the hippocampus proper. The present data implicate the proteins Emx2, Pax6 and Ngn2 as putative molecular signals controlling the fate of progenitor cells of the adult primate hippocampus.

Animals↗
PubMed2006

Long-term effect of early discharge on sEPSC and [Ca2+]i in developing neurons.

To study the long-term changes induced in immature rat cortical neuronal cultures by transient exposure to an Mg(2+)-free treatment, at cultured day 6, cells were assigned into three groups, based on the mediums they were transiently exposed to as follows: control group 1 (CONT1) was exposed to Dulbecco's Modified Eagle's Medium (DMEM), control group 2 was exposed to a physiological solution (PS), and the magnesium-free physiological solution group (MGFPS) was exposed to the same medium as CONT2 except for the removal of magnesium. Following a 3-h exposure, the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSC) were recorded and intracellular calcium concentrations ([Ca2+]i) were measured. Compared to the CONT1 and CONT2 groups, the MGFPS group displayed a significantly greater amplitude (at d6, d7, d9, and d12) and frequency (at d6, d7, and d9) of sEPSC (p<0.05). Also, both the resting and peak intracellular calcium levels were significantly greater in the MGFPS group at days 6, 7, 9, 12 and 17 (p<0.05). The rise time (time from resting level to peak level of intracellular calcium following NMDA application) was significantly shorter in the MGFPS group at culture days 7 and 17 and significantly longer at culture day 12 (p<0.05). Finally, we compared the percentage of cortical neurons expressing neuron-specific enolase (NSE) and found that there were no significant differences in the number of NSE positive neurons among three groups at days 7, 12, and 17. Our results suggests that there are long-term changes in sEPSCs and [Ca2+]i in cultured rat cortical neurons following exposure to Mg2+-free environment without cell loss.

Analysis of Variance↗
PubMed2006

Long-term fate of neural precursor cells following transplantation into developing and adult CNS.

Successful strategies for transplantation of neural precursor cells for replacement of lost or dysfunctional CNS cells require long-term survival of grafted cells and integration with the host system, potentially for the life of the recipient. It is also important to demonstrate that transplants do not result in adverse outcomes. Few studies have examined the long-term properties of transplanted neural precursor cells in the CNS, particularly in non-neurogenic regions of the adult. The aim of the present study was to extensively characterize the fate of defined populations of neural precursor cells following transplantation into the developing and adult CNS (brain and spinal cord) for up to 15 months, including integration of graft-derived neurons with the host. Specifically, we employed neuronal-restricted precursors and glial-restricted precursors, which represent neural precursor cells with lineage restrictions for neuronal and glial fate, respectively. Transplanted cells were prepared from embryonic day-13.5 fetal spinal cord of transgenic donor rats that express the marker gene human placental alkaline phosphatase to achieve stable and reliable graft tracking. We found that in both developing and adult CNS grafted cells showed long-term survival, morphological maturation, extensive distribution and differentiation into all mature CNS cell types (neurons, astrocytes and oligodendrocytes). Graft-derived neurons also formed synapses, as identified by electron microscopy, suggesting that transplanted neural precursor cells integrated with adult CNS. Furthermore, grafts did not result in any apparent deleterious outcomes. We did not detect tumor formation, cells did not localize to unwanted locations and no pronounced immune response was present at the graft sites. The long-term stability of neuronal-restricted precursors and glial-restricted precursors and the lack of adverse effects suggest that transplantation of lineage-restricted neural precursor cells can serve as an effective and safe replacement therapy for CNS injury and degeneration.

Age Factors↗
PubMed1999

Use of brain slices in the study of pathogenic role of inducible nitric oxide synthase in cerebral ischemia-reperfusion.

We have recently demonstrated that inducible nitric oxide synthase (iNOS) is expressed in rat forebrain slices exposed to oxygen and glucose deprivation (OGD). Now, we have found that the expression of iNOS after OGD is time-dependent since 20 min of OGD produces the appearance of iNOS at earlier times than 10 min of OGD. OGD also causes neurotoxicity in this model, as revealed by the increase in excitatory amino acid, neuron specific enolase and lactate dehydrogenase (LDH) efflux to the incubation solution. Finally, the administration of the NMDA receptor antagonist MK-801 (100 nM) inhibits both the expression of iNOS and the release of LDH. Our findings demonstrate that this method may be considered an useful in vitro model of ischemia-reperfusion to determine the therapeutic role of neuroprotective tools.

Animals↗
PubMed1995

Gliomatosis peritonei combined with mature ovarian teratoma: immunohistochemical observations.

Gliomatosis peritonei (GP) is the metastatic implantation of glial cells within the peritoneal cavity of patients with ovarian teratomas. The case of a young woman is presented, who initially developed a mature teratoma in the left ovary that was surgically removed. Nine years later a mature teratoma in the right ovary was excised, upon which GP was found in the greater omentum. To identify the cellular composition of the ovarian teratoma and of the omental implants, immunostainings were performed using antibodies against glial and neuronal antigens as well as against determinants of hematopoietic cells. In the teratoma the neuroectodermal part was strongly HNK-1-positive and contained GFAP- and vimentin-positive astrocytes and some NSE-positive neuron-like cells. In addition, neuroectodermal tissue was infiltrated by numerous CD68-positive macrophages/histiocytes and CD20-positive B lymphocytes. The omental nodules consisted of astrocytes, which expressed GFAP, vimentin and desmin. The implants also contained macrophages/histiocytes, which exhibited morphologic features reminiscent of microglial cells. In GP, macrophages might release glia-promoting trophic factors, which could allow the neural component of ovarian teratoma to implant in the peritoneal cavity and survive there for many years. Macrophage-derived factors might induce astroglial differentiation, which could explain why the peritoneal implants are mostly mature even when they originate from immature teratomas.

Adolescent↗
PubMed2003

Identification of a novel plasmin(ogen)-binding motif in surface displayed alpha-enolase of Streptococcus pneumoniae.

The interaction of Streptococcus pneumoniae with human plasmin(ogen) represents a mechanism to enhance bacterial virulence by capturing surface-associated proteolytic activity in the infected host. Plasminogen binds to surface displayed pneumococcal alpha-enolase (Eno) and is subsequently activated to the serine protease plasmin by host-derived tissue plasminogen activator (tPA) or urokinase (uPA). The C-terminal lysyl residues of Eno at position 433 and 434 were identified as a binding site for the kringle motifs of plasmin(ogen) which contain lysine binding sites. In this report we have identified a novel internal plamin(ogen)-binding site of Eno by investigating the protein-protein interaction. Plasmin(ogen)-binding activity of C-terminal mutated Eno proteins used in binding assays as well as surface plasmon resonance studies suggested that an additional binding motif of Eno is involved in the Eno-plasmin(ogen) complex formation. The analysis of spot synthesized synthetic peptides representing Eno sequences identified a peptide of nine amino acids located between amino acids 248-256 as the minimal second binding epitope mediating binding of plasminogen to Eno. Binding of radiolabelled plasminogen to viable pneumococci was competitively inhibited by a synthetic peptide FYDKERKVYD representing the novel internal plasmin(ogen)-binding motif of Eno. In contrast, a synthetic peptide with amino acid substitutions at critical positions in the internal binding motif identified by systematic mutational analysis did not inhibit binding of plasminogen to pneumococci. Pneumococcal mutants expressing alpha-enolase with amino acid substitutions in the internal binding motif showed a substantially reduced plasminogen-binding activity. The virulence of these mutants was also attenuated in a mouse model of intranasal infection indicating the significance of the novel plasminogen-binding motif in the pathogenesis of pneumococcal diseases.

Amino Acid Motifs↗
PubMed1996

Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation.

We have examined the regulation of neuron-specific gamma-enolase gene (NSE) expression in oligodendrocytes at various steps of their differentiation/maturation. We have demonstrated for the first time that NSE is expressed in oligodendroglial cells in vitro and in vivo, and only at a certain stage of differentiation. A heterogeneity of the gamma subunit was observed in cultured oligodendrocytes and the same one was found in adult rat brain. The level of gamma mRNA increased when precursor cells differentiated into oligodendrocytes. By contrast, no significant change in alpha-enolase gene expression was observed. High NSE (gamma gamma and alpha gamma) enolase activity was detected in cultured oligodendrocytes. Treatment with basic fibroblast growth factor, which stimulates the proliferation of oligodendrocyte precursor cells and reversibly blocks their differentiation, resulted in lower alpha gamma- and gamma gamma-enolase activities in these cells, but it enhanced alpha alpha-enolase activity slightly. These data indicate that gamma-enolase gene expression is associated with the differentiation of the oligodendrocytes and that it is repressed in adult fully mature cells.

Aging↗
PubMed1999

Copurification of selected glycolytic enzymes with retinal S-antigen (arrestin) by hydroxyapatite agarose chromatography of bovine retina.

PURPOSE: A variety of methods have been developed for the purification of S-antigen but a simple and rapid procedure based on hydroxyapatite-agarose (HA) adsorbtion is most widely used. In the present study, we investigated the nature of proteins purified with the aid of HA chromatography. METHODS: After elimination of retinal S-antigen by HA, the soluble extract of retinal tissue was readsorbed on HA. The proteins were thereafter desorbed by 10 to 500 mM phosphate buffer gradient. Two peaks obtained by SDS-PAGE were used for the generation of specific antisera for subsequent analysis by ELISA and Western blotting. RESULTS: Four proteins (two 48 kDa , one 50 kDa and one 46 kDa) were obtained in this manner. Partial amino acid sequencing permitted the identification of these proteins as alpha-enolase (48 kDa), gamma-enolase (48 kDa), Glucose-6-phosphate-Isomerase (50 kDa) and aspartate-amino-transferase (46 kDa). CONCLUSION: The selected glycolytic enzymes co-purified with retinal S-antigen by hydroxyapatite agarose chromatography of bovine retina.

Amino Acid Sequence↗
PubMedDate not supplied

Energy status, ubiquitin proteasomal function, and oxidative stress during chronic and acute complex I inhibition with rotenone in mesencephalic cultures.

Complex I impairment with rotenone produces damage though a mechanism thought to be distinct from effects on mitochondrial respiration. The outcome of chronic rotenone on energy status in relation to toxicity, however, is unknown. To examine this, mesencephalic cultures were exposed to chronic, low-dose rotenone (5-100 nM, 8 days in vitro) or acute, high-dose rotenone (500 nM, 1-24 h), and ATP/ADP levels and toxicity were measured. Chronic exposure to 5-50 nM rotenone produced selective dopamine cell loss. High-dose rotenone produced nonselective damage at all exposure times. Chronic, low-dose rotenone (37.5 nM) decreased ATP/ADP gradually over several days to 40% of controls, whereas high-dose rotenone (500 nM, 1-6 h), collapsed ATP/ADP by 1 h of exposure. The ubiquitin proteasomal pathway, an ATP-dependent pathway, is implicated in Parkinson's disease and, thus, various rotenone exposures were examined for effects on ubiquitin proteasomal function. Chronic, low-dose rotenone (25-50 nM, 8 days), but not acute, high-dose rotenone (500 nM, 1-6 h), caused accumulation of ubiquitinated proteins, E1-ubiquitin activation, and increased proteasomal activities prior to toxicity even though both exposures increased free radical production. Findings show that selective dopamine cell loss and alterations in ubiquitin proteasomal function only occur with rotenone exposures that partially maintain ATP/ADP. High concentrations of rotenone that collapse energy status kill neurons in a nonselective manner independent of the ubiquitin proteasomal pathway.

Adenosine Triphosphate↗
PubMed1997

Glial choristoma in the oral cavity: histopathologic and immunohistochemical features.

This report describes the morphologic and immunohistochemical features of two cases of glial choristoma arising in the palate. The bulk of the lesions consisted of mature neuroglial tissue admixed with salivary glands, adipose tissue and lymphoid aggregates in case 1 and of cartilage, bone and foci of smooth muscle cells in case 2. In addition, case 2 showed choroid plexus and melanin-containing epithelium. Neuroglial tissue was intensely positive for CD57 as well as for glial fibrillary acidic protein, S-100 protein and vimentin. Neuron-specific enolase and neurofilament were focally or weakly positive. Proliferating cell nuclear antigen was negative in case 1 but sparsely positive in case 2. These features reflect the fact that glial choristoma is a developmental malformation of heterotopic central nervous tissue with limited growth potential.

Adipose Tissue↗
PubMed1999

Identification, N-terminal region sequencing and similarity analysis of differentially expressed proteins in Paracoccidioides brasiliensis.

Paracoccidioides brasiliensis is the causal agent of paracoccidioidomycosis, which is a systemic mycosis in Latin America. This human pathogen is a dimorphic fungus existing as mycelium (26 degrees C) and in infected tissues as a yeast form (36 degrees C). The in vitro differentiation process is reversible and dependent on temperature shift. In the present study, the total proteins from both forms of P. brasiliensis (isolate Pb01) were analysed by two-dimensional electrophoresis. Differentially expressed proteins were identified. Two of these proteins, PbM46 (mycelium) and PbY20 (yeast), were submitted to automated protein sequencing of their N-terminal regions. The 15 amino acid residue sequence of PbM46, AITKIFALKVYDSSG, is similar to enolases from several sources, and specially those from Saccharomyces cerevisiae (80%) and Candida albicans (67%), when compared to the NR database at NCBI using the BLASTP program. The 34 amino acid residue sequence of PbY20, APKIAIVFYSLYGHIQKLAEAQKKGIEAAGGTAD, could probably represent an allergen protein since it is very similar (90%) to the minor allergen protein of Alternaria alternata and 82% similar to the allergen protein of Cladosporium herbarum. This comparative analysis of proteins from mycelium and yeast forms has allowed the identification and characterization of differentially expressed proteins, probably related to differential gene expression in P. brasiliensis.

Amino Acid Sequence↗
PubMed2000

Histopathological variants of central neurocytoma: Report of 10 cases.

Central neurocytoma is a rare neuronal tumor affecting young adults and usually located in the lateral ventricles. Post-operative prognosis is generally good. Histologically, central neurocytoma is composed of isomorphous small round or ovoid cells alternating with irregularly shaped patches of fibrillary matrix similar to the neuropile. In a series of 10 cases, two central neurocytomas were histologically "atypical" at first examination. One was intra-ventricular, and the second had an intra-parenchymatous juxta-ventricular location. Both were highly cellular with mitotic activity, and tumor necrosis was seen in one. Neuronal differentiation was assessed by synaptophysin immunoreactivity in all 10 cases and by ultrastructural examination in four, including the two "atypical" forms. Neuronal differentiation was less marked in these "atypical" forms, one also presenting focal GFAP immunoreactivity. The proliferative potential was determined by MIB-1 labeling index and compared with clinical outcome. The eight classical central neurocytomas had a MIB-1 labeling index < 2.3%, whereas the two "atypical" forms had a MIB-1 labeling index > 5.2% and both recurred. We think that there is a spectrum of small-cell neuronal tumors. The two extremes could be the central neurocytoma and the primary cerebral neuroblastoma, while the intermediate forms might be qualified as "atypical neurocytoma". In our series, the histological and immunohistochemical criteria of biological aggressiveness appeared to be high mitotic activity, tumor necrosis, loss of neuronal differentiation and high MIB-1 labelling index.

Adult↗
PubMed1988

Paragangliomas of the head and neck: immunohistochemical neuroendocrine and intermediate filament typing.

Twenty-nine paragangliomas of the head and neck region including 20 glomus jugulare (GJ) and nine carotid body (CB) tumors were evaluated for the presence of neuroendocrine and intermediate filament antigens. Immunohistochemistry on formalin-fixed, paraffin-embedded tissue was used to identify: S-100 protein (S-100); neuron-specific enolase (NSE); chromogranin A (CHA); serotonin (SER); synaptophysin (SYN); cytokeratin (CK); neurofilament (NF); desmin (DES); vimentin (VIM); and glial fibrillary acidic protein (GFAP). S-100 protein staining of sustentacular cell nuclei and cytoplasm was found in all tumors and was present in chief cells in 4 of 20 GJ and 3 of 9 CB tumors. All tumors stained with at least three neuroendocrine markers (29 of 29 NSE, 28 of 29 SYN, 26 of 29 CHA, 25 of 29 SER). CK was detected in 2 GJ and 1 CB tumor using anticytokeratins AE 1/3 and CAM 5.2. Neurofilament protein could not be demonstrated in fixed material, and all tumors were negative for GFAP and desmin. Vimentin was inconsistently detected in chief and sustentacular cells. We conclude that, in formalin-fixed material, paragangliomas have S-100 protein staining of sustentacular cells with chief cells containing antigens associated with neuroendocrine differentiation. The presence of CK in some paragangliomas is consistent with recent tissue culture studies demonstrating immunoblot confirmation of CK in pheochromocytomas and represents a potential source of immunohistologic misinterpretation in diagnosis, unless a panel of markers is utilized.

Antibodies↗
PubMed1989

Differentiation in medulloblastomas: immunohistochemical study of twenty-one cases.

Twenty-one cases of medulloblastoma (MB), 20 corresponding to the classical type and 1 to the desmoplastic variant (DPM), were studied immunohistochemically with glial fibrillary acidic protein (GFAP), S-100 protein (S-100P), neuron-specific enolase (NSE) and 200-kd neurofilaments (NF) in order to assess their differentiation potential. Their respective positivities in neoplastic cells were: 42% for GFAP, 47% for S-100P, 61% for NSE and absence of NF. Isolated neoplastic cells (e.g., cells lacking processes and with scanty cytoplasm), appeared positive for neuroglial markers (GFAP and S-100P). Most cases, however, showed positive reactive neuroglial cells. NF were never found in neoplastic cells, but in trapped neuronal processes. In most cases, large numbers of cells had high positivity to NSE. Cells of lucent islands of DPM were positive for GFAP and S-100P, while Homer-Wright type rosettes showed positive only for NSE. The above results support a neuroglial differentiation in MB. NSE was considered a nonspecific marker for neuroblastic cells.

Adolescent↗
PubMed1984

Interconversion of biological characteristics of small cell lung cancer depending on culture conditions.

Two distinct cell lines were obtained from a single heterotransplanted tumor which had originated from a primary focus of small cell carcinoma of the lung (SCCL). They were maintained separately from the beginning in culture media with and without fetal calf serum supplementation. Cells in the serum-free medium grew mostly floating in loose aggregates and showed poor cell cohesiveness, scanty cytoplasm and a few intracytoplasmic small dense-cored granules; all of these features are characteristics of oat cell type SCCL. On the other hand, cells in the serum-supplemented medium grew mostly floating in flatter and more closely associated clumps, were larger, and showed increased cell cohesiveness, occasional tubular structures, better developed organelles including dense-cored granules, and an increased number of cell attachments; these features are characteristics of intermediate cell type SCCL. The modal number of chromosomes differed from each other. Neuron-specific enolase (gamma enolase) and aromatic L-amino acid decarboxylase (ADC) activities in cell pellets were significantly higher in both lines than in control non-small cell lung cancer cell lines. The alpha/gamma type enolase ratio was lower, as was the ADC activity, in serum-free cultures than in serum-supplemented cultures. Interchange of the culture medium induced changes of the growth pattern and cell type from "oat cell type" to "intermediate cell type" and vice versa. The chromosomal number also partially changed. These findings suggest that cultured cells of SCCL alter their growth pattern and cell type depending on the culture conditions and that the selective growth of one cell type might then take place.

Animals↗