TI-201 SPECT in pseudotumoral multiple sclerosis.
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Brain↗
Biomedical subjects
S Vidal
Publications and source records attributed to S Vidal.
Anticipating endoplasmic reticulum stress. A novel early response before pathogenesis-related gene induction
When it is attacked by a pathogen, a plant produces a range of defense-related proteins. Many of these are synthesized by the rough endoplasmic reticulum (RER) to be secreted from the cell or deposited in vacuoles. Genes encoding endoplasmic reticulum (ER)-resident chaperones, such as the lumenal binding protein (BiP), are also induced under these conditions. Here, we show that BiP induction occurs systemically throughout the plant. Furthermore, this induction occurs rapidly and precedes expression of genes encoding pathogenesis-related (PR) proteins. The underlying signal transduction pathway was shown to be independent of the signaling molecule salicylic acid and the unfolded protein response pathway. In addition, BiP induction was independent of PR gene induction. Overproduction of BiP alone was not sufficient to cause induction of PR gene expression; however, limiting the amount of BiP in the ER lumen via superimposed ER stress inhibited the induction of PR gene expression. We propose that the induction of BiP expression during plant-pathogen interactions is required as an early response to support PR protein synthesis on the RER and that a novel signal transduction pathway exists to trigger this rapid response.
Journal Article↗
Increased level of p21 in human ovarian tumors is associated with increased expression of cdk2, cyclin A and PCNA.
We have demonstrated over-expression of the cyclin-dependent kinase inhibitor p21 in various ovarian-cancer cell lines as well as in ovarian-tumor biopsies. This increase in p21 expression relative to that observed in normal ovarian epithelial cells is unrelated to proliferation index. In the present study, we found that p21 is functional, since the protein extracted from IGROVI cells is still able to inhibit cdk2-kinase activity. We then investigated how IGROVI cells overcome the growth-inhibitory function of p21. Immunofluorescence assays and subcellular fractionation showed that p21 is located in cytoplasm and nucleus both in normal and in tumoral cells. Compared with normal ovarian epithelial cells in culture, the increase in level of p21 in IGROVI cells was found to be associated with increased expression of cdk2, cyclin-A and PCNA proteins. In IGROVI cells, p21 is associated with inactive cdk2/cyclin-A complex, indicating that it acts as an inhibitory factor rather than an assembly factor. Over-expression of cdk2 and of cyclin A observed in IGROVI cells allows them to escape to p21-inhibitory activity. The fact that cells from ovarian-tumor biopsies exhibited a concomitant increase in p21 and in its partners cdk2 and PCNA suggest that ovarian-tumor cells can tolerate high levels of functional p21 via over-expression of other cell-cycle-regulatory proteins.
Animals↗
Loci predisposing to autoimmunity in MRL-Fas lpr and C57BL/6-Faslpr mice.
Background genes determine the incidence and severity of lymphoaccumulation and histopathologic manifestations of systemic autoimmunity in mice homozygous for the apoptosis-defective Faslpr mutation. By interval mapping of 274 F2 mice intercrossed between MRL-Faslpr (severe disease) and C57BL/6-Faslpr (minimal disease), four loci were identified with significant linkage to lymphadenopathy and/ or splenomegaly on chromosomes 4, 5, 7, and 10, which were named lupus in (MRL-Faslpr x B6-Faslpr)F2 cross1-4 (Lmb1-4), respectively. Lmb1, -2, and -3 were also linked to the production of anti-dsDNA antibodies, but not glomerulonephritis, whereas Lmb4 was associated with glomerulonephritis. Lmb2, -3, and -4 were inherited from the MRL background, but interestingly, Lmb1 was derived from the C57BL16-Faslpr. Nevertheless, each locus, regardless of the strain of origin, appeared to act in an additive manner, although certain combinations were more effective. Only a single suggestive locus on chromosome 1 could be correlated with arthritis. The identification of loci with highly significant linkage to disease manifestations in Faslpr strains will make it possible to map and clone new genetic defects contributing to autoimmunity.
Animals↗
Simultaneous localization of Pit-1 protein and gonadotropins on the same cell type in the anterior pituitary glands of the rat.
Pit-1 is a prototypic member of the POU transcription factor family and plays a critical role in pituitary-specific action of growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) beta-subunit genes. The purpose of the present study was to elucidate the changes in the expression of the Pit-1 product in the pituitary of pregnant rats employing an improved double-immunohistochemical method. The positive cells showed nuclear immunoreactivity and Pit-1 protein was frequently observed in the nuclei of many cells which were also immunopositive for GH, PRL, and betaTSH. Unexpectedly, a significant number of pituitary cells containing both Pit-1 and gonadotropins were also observed. These cells were usually distributed near blood vessels that supply the pituitary. While a prominent increase in the percentage of Pit-1/PRL, Pit-1/beta-luteinizing hormone and Pit-1/beta-follicle-stimulating hormone immunoreactive cells was observed in pregnant rats, the percentage of Pit-1/GH immunoreactive cells was strongly decreased. In contrast, no significant differences in the percentage of Pit-1/betaTSH doubly immunolabeled cells were noticed. Our findings strongly support the hypothesis that PRL could coexist in the Pit-1 immunopositive gonadotropes. Although Pit-1 protein was not detected in the nuclei of corticotropes, the existence of these cells in the rat pituitary cannot be excluded.
Animals↗
Horse bite injury.
Bite wounds are relatively frequent, the order of frequency being, dogs, cats and humans. The clinical importance of other types of bites depends on the severity of the injury or any subsequent infection. We report on the case of a woman bitten on her thigh by a horse, producing severe haematoma, fat necrosis and muscle rupture, without an external wound. We emphasize the importance of the ultrasound examination in the evaluation of the extent of the crush injury.
Adult↗
Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line.
It has been shown recently that expression of p21 is enhanced by paclitaxel. This cytotoxic compound induces mitotic spindle damage resulting in blockade of the mitotic cell cycle associated or not with apoptotic cell death. In the present study, we showed that, in MCF-7 cells, paclitaxel induced accumulation of p21 in cells with a G2/M DNA content, corresponding to cells either in abnormal mitosis or in an interphase-like state (decondensed chromatin) with multiple nuclei. In MCF-7 cells, the increase in p21 was subsequent to the mitotic arrest and was associated with the exit from abnormal mitosis leading to formation of cells with micronuclei. In this cell line, we noted a relationship between the elevation of p21 expression and the inhibition of p34cdc2 activity. High levels of p21 protein were also found to be associated with inactive p34cdc2/cyclin B protein complex after treatment with paclitaxel. Treatment with p21 antisense oligonucleotide partially blocked induction of p21 expression by paclitaxel and significantly reduced survival of MCF-7 cells exposed to this agent. In NIH-OVCAR-3 cells, which are deficient in basal and paclitaxel-induced p21 expression, paclitaxel led to a prolonged activation of p34cdc2 and a delayed mitotic exit associated with apoptotic cell death. These observations suggest that p21 is not required for the mitotic arrest in response to paclitaxel, but argue in favor of a role for this inhibitor in facilitating the exit from abnormal mitosis. This effectively enhances cell survival after paclitaxel-induced spindle damage.
Adenocarcinoma↗
Rhamnogalacturonan II, a dominant polysaccharide in juices produced by enzymic liquefaction of fruits and vegetables.
Rhamnogalacturonan II (RG-II), a small complex pectic polysaccharide, is released from apple (Malus domestica), carrot (Daucus carota), and tomato (Solanum lycopersicum) by treatment with two commercial liquefying enzyme preparations. RG-II was isolated by size-exclusion chromatography from apple, tomato, and carrot juices obtained by enzymic liquefaction. All the RG-IIs contained the diagnostic sugars, apiose, 2-O-methyl-L-fucose, 2-O-methyl-D-xylose, aceric acid, Kdo and Dha. Glycosyl-linkage compositions of the neutral and acidic sugars, including aceric acid, were consistent with the hypothetical model described for sycamore RG-II confirming the conservation of RG-II in plants. Thus, when pectinolytic enzyme preparations are used to process fruits and vegetables, RG-II is released as a main soluble polysaccharide fraction while other pectic polysaccharides are heavily degraded.
Carbohydrate Conformation↗
Ultrastructural and immunocytochemical studies of prolactin-secreting cells in adenohypophysis of the mink (Mustela vison).
This investigation aimed to identify, by the double immunogold procedure, the ultrastructural characteristics of prolactin (PRL) cells in the mink. Such cells showed a marked pleomorphism and had a close topographic relationship with growth hormone cells. A common morphological characteristic of PRL cells in all stages of mink development was the presence of round secretory granules, in contrast to changes in the ultrastructural characteristics of PRL cells with physiological state and photoperiod. Thus PRL cells in prepubertal, pubertal, and sexually inactive adult mink, killed under a short-day photoperiod, showed little development of the organelles but a significantly increased cytoplasmic electron density. In sexually active mink and in lactating females under long-day conditions, PRL cells had a highly developed cytoplasmic organelle structure consisting mainly of rough endoplasmic reticulum. The morphometric study demonstrated that the mean diameter of the secretory granules similarly varied in both sexes. Pubertal mink had PRL cells with smaller secretory granules (female 74.1 +/- 0.6 nm, male 80.4 +/- 1.7 nm), whereas adult mink killed under a long-day photoperiod presented PRL cells with larger secretory granules (female 194.5 +/- 2.2 nm, male 203.3 +/- 1.7 nm). The changes in the ultrastructural characteristics of PRL cells during the annual cycle suggest a photoperiodic influence upon these cells. In addition the heterogeneity in ultrastructural characteristics and storage characteristics of PRL in some adult mink may suggest a varying metabolic role for PRL under certain, as yet not fully characterized, conditions.
Aging↗
Description of two types of mammosomatotropes in mink (Mustela vison) adenohypophysis: changes in the population of mammosomatotropes under different physiological conditions.
The present study was undertaken to clarify the existence of mammosomatotropes (MS cells) in the mink adenohypophysis and their possible involvement in the interconversion of mammotrope and somatotrope cells under different physiological conditions: prepubertal, pubertal and adulthood. Electron microscope immunocytochemistry was used to detect growth hormone (GH) and prolactin (PRL) immunoreactivities in the anterior pituitary gland of mink. Primary antisera raised in rabbit (human anti-GH, NIDDK-AFP-1613102481; human anti-PRL, NIDDK-AFP-55781789) were localized with appropriate species-specific antisera coupled to colloidal gold particles of different sizes. MS cells were most frequently observed in adult mink. Double labeling for GH and PRL was presented in two types of MS cells. MS1 cells, observed only in adults, showed an irregular morphology, with many cytoplasmic processes. Within their cytoplasm there were numerous rounded secretory granules of approximately 135 nm mean diameter. In MS1 cells three types of secretory granules were identified. The most numerous contained only PRL. The least frequent contained only GH and the third type contained GH and PRL and appeared in an intermediate quantity. MS2 cells, observed in all age groups, presented a rounded morphology. These cells had a voluminous cytoplasm which showed little development of the organelles and contained a large number of rounded and very electron-dense secretory granules which measured about 160 nm mean diameter. Within MS2 cells two types of secretory granules, according to their immunolabeling, were observed. Monohormonal granules containing GH were the more abundant while bihormonal granules, containing GH and PRL, were present to a lesser degree. Data presented in this report suggest that MS cells could play a role in the interconversion of somatotropes into mammotropes in mink.
Animals↗
Nonspecific resistance to Mycobacteria: the role of the Nramp1 gene.
The genus Mycobacteria consists of over 50 species that include two of the best-known human pathogens, M. tuberculosis and M. leprae, the causes of tuberculosis (TB) and leprosy, respectively. Whereas the spread of leprosy currently appears to be under control, there are presently about 30 million active cases of TB worldwide, with an alarming increase in the number of multidrug resistant case of M. tuberculosis. As strategies for antibiotic intervention against TB become more limited, it is imperative to develop new therapeutic approaches against this oppressive disease. One promising avenue is to characterize the host genes and gene products which regulate resistance to mycobacterial infections. In the mouse, resistance and susceptibility to intracellular growth of Mycobacteria in macrophages is controlled by the Bcg (Nramp1) gene, which has now been cloned and shown to encode a macrophage transmembrane protein with a putative transporter function. Sequencing of Nramp1 revealed that susceptibility to infection is associates with a single, nonconservative glycine to aspartic acid substitution at position 169 (G169D). Although the intracellular location of the Nramp1 protein in macrophages has not yet been determined, a phagosomal site has been postulated. Consistent with the proposed role of Nramp1 in macrophage activation, recent studies of the Nramp1 promoter region have revealed consensus sequences associated with responsiveness to IFN-gamma and LPS. Finally, a total of 11 polymorphisms have been identified within the human NRAMP1 gene which are being used to test for linkage of NRAMP1 alleles with human susceptibility to TB and leprosy.
Animals↗
Structural characterization of red wine rhamnogalacturonan II.
The pectic polysaccharide rhamnogalacturonan II (RG-II), which accounts for approximately 20% of the ethanol-precipitable polysaccharides in red wine, has been isolated from wine polysaccharides by anion-exchange chromatography. Four fractions enriched with RG-II were obtained and the RG-II then purified to homogeneity by Concanavalin A affinity and size-exclusion chromatographies. The glycosyl-residue compositions of the four RG-IIs are similar; all the RG-IIs contain the monosaccharides (apiose, 2-O-methyl-L-fucose, 2-O-methyl-D-xylose, Kdo, Dha, and aceric acid) that are diagnostic of RG-II. The glycosyl-linkages of the neutral and acidic sugars, including aceric acid, were determined simultaneously by GC-EIMS analysis of the methylated alditol acetates generated from per-O-methylated and carboxyl-reduced RG-II. Two of the RG-IIs contain boron, most likely as a borate di-ester that cross-links two molecules of RG-II together to form a dimer. The dimer contains 3'- and 2,3,3'-linked apiosyl residues whereas the monomer contains only 3'-linked apiosyl residues which suggests that the borate di-ester is located on at least one of the apiosyl residues of RG-II. Although the wine RG-IIs all have similar structures they are not identical since they differ in the length and degree of methyl-esterification of the RG-II backbone and in the presence or absence of borate di-esters. Nevertheless, these studies show that the major structural features of wine and primary cell wall RG-II are conserved.
Borates↗
The role of BALB/c donor CD8+ lymphocytes in graft-versus-host disease in (BALB/c x A/J)F1 (CAF1) mice.
To investigate the role of donor T lymphocyte subsets in the development of chronic graft-vs-host disease (GVHD) induced in (BALB/c x A/J)F1 (CAF1) mice by injecting BALB/c lymphoid cells, we analyzed the effect that CD8+ cell removal from donor inoculum has on the manifestation of the disease. Compared with age- and sex-matched CAF1 mice injected with whole lymphocyte inoculum, CAF1 mice injected with CD8(+)-depleted inoculum exhibited: 1) a higher incidence and exacerbation of nephritis by immunocomplexes; 2) higher (five- to sevenfold) spontaneous IL-4 production; 3) higher frequency titer and precocity of anti-dsDNA, anti-histone, and IgM and IgG rheumatoid factors; 4) a dramatic change in the frequency and titer of anti-U1 small nuclear ribonucleoprotein Abs; and 5) a markedly decreased engraftment (10- to 15-fold) on BALB/c donor lymphocytes. In contrast, rheumatoid arthritis-like disease, a later clinical manifestation of the GVHD in CAF1 + BALB/c model, is not present in the CD8(+)-depleted model (CAF1 + CD8-BALB/c). Considered together, these data suggest that CD8+ donor T lymphocytes play an important role in the degree of chimerism, modulation of the response to autoantigens, and clinical aspects developed in the GVHD model presented here.
Animals↗
The Bcg/Ity/Lsh locus: genetic transfer of resistance to infections in C57BL/6J mice transgenic for the Nramp1 Gly169 allele.
The murine Bcg/Ity/Lsh locus determines the susceptibilities of inbred strains to infection with unrelated intracellular parasites, such as Mycobacterium bovis, Salmonella typhimurium, and Leishmania donovani. A candidate for Bcg/Ity/Lsh, designated Nramp1, has been recently identified and shown to encode a novel integral membrane protein that is expressed exclusively in professional phagocytes but whose function remains unknown. In inbred strains, the susceptibility to infection is associated with a single glycine-to-aspartic acid substitution at position 169 (G169D) in the predicted TM4 of the protein. To confirm the candidacy of Nramp1 as Bcg/Ity/Lsh and to determine the importance of the G169D mutation on Nramp1 function, we constructed transgenic mice in which the G169 allele of Nramp1 was transferred onto the background of a homozygous D169 allele. These transgenic mice were analyzed for their sensitivity to infections under the control of Bcg/Ity/Lsh. The transgene constructed for these studies contained the entire Nramp1G169 gene together with approximately 5 kb of sequences upstream of the transcription initiation site of this gene. We observed that these sequences were sufficient to direct Nramp1G169 expression in transgenic macrophages, resulting in the appearance of a mature protein of 90 to 100 kDa over a background of Nramp1G169 characterized by the complete absence of the mature Nramp1 polypeptide. The appearance of the Nramp1G169-encoded protein in transgenic macrophages was concomitant with the emergence of resistance to infection by M. bovis BCG, as measured by the extent of bacteria] replication in the spleen, and by S. typhimurium, as measured by survival after an intravenous challenge. The gain of function detected in transgenic Nramp1G169 animals establishes unambiguously that Nramp1 and Bcg/Ity/Lsh are allelic.
Alleles↗
Transforming growth factor beta 1-induced apoptosis in human ovarian carcinoma cells: protection by the antioxidant N-acetylcysteine and bcl-2.
We have previously shown that transforming growth factor beta 1 (TGF-beta 1) inhibits growth and induces apoptosis in NIH-OVCAR-3 ovarian adenocarcinoma cells. In this study, we investigated the role of the reactive oxygen species in the TGF-beta 1 signaling pathways. We found that both TGF-beta 1 and an oxidant, hydrogen peroxide, rapidly increase the expression of c-fos and c-jun genes and induce cell death by apoptosis; these effects are inhibited by the antioxidant N-acetylcysteine. In contrast, N-acetylcysteine did not influence TGF-beta 1-mediated cell cycle arrest at the G1-S transition. TGF-beta 1 down-regulated the endogenous expression of the anti-apoptotic bcl-2 gene, and overexpression of this gene inhibited TGF-beta 1-induced apoptosis. Taken together, these results suggest that TGF-beta 1 activates multiple signaling pathways in the NIH-OVCAR-3 cell line and that the reactive oxygen species play a role in the early gene responses and apoptosis induced by TGF-beta 1.
Acetylcysteine↗
Expression of p21WAF1/CIP1 is heterogeneous and unrelated to proliferation index in human ovarian carcinoma.
The growth-inhibitory protein p21WAF1/CIP1 is a potent inhibitor of various cyclin-dependent kinases, the expression of which is regulated at the transcriptional level by p53-dependent and -independent mechanisms. We examined p21WAF1/CIP1 mRNA and protein expression in 5 human ovarian-adenocarcinoma cell lines, 1 primary culture of normal surface epithelium and 17 human ovarian-tumor specimens. In culture cells, the p21WAF1/CIP1 protein was expressed in normal ovarian epithelial cells and at a high level in the adenocarcinoma 2008 and IGROV-1 cell lines. p21 WAF1/CIP1 expression was undetectable at the mRNA and protein levels in the NIH-OVCAR-3 and SKOV-3 ovarian-adenocarcinoma cell lines which are respectively mutated and deleted in the p53 gene. Heterogeneous expression of p21WAF1/CIP1 observed in ovarian-cancer cell lines in culture was also found in vivo on tumor specimens. p21WAF1/CIP1 expression is undetectable in 25% of the ovarian biopsies examined. Since it has been found that the p53 gene is mutated in 79% of ovarian cancer, the absence of p21WAF1/CIP1 expression in 25% of these ovarian cancer could not be correlated with p53 mutation. The proliferation index of the 17 tumors showed great variation from one tumor to another. However, no significant correlation was found between p21WAF1/CIP1 expression and the proliferation rate of the tumors.
Adenocarcinoma↗
Characterization of five type II arabinogalactan-protein fractions from red wine of increasing uronic acid content.
Five arabinogalactan-protein conjugates (AGP) were separated from red wine by two successive anion-exchange chromatography steps and further purified to apparent homogeneity by affinity and size-exclusion chromatography. Together they represent more than 40% of total wine polysaccharides, confirming the abundance of AGPs in red wine. The five purified fractions had a common arabinogalactan core with characteristics typical of wine type II AGPs, but differed mainly in their uronic acid content, as evidenced by differences in the strength of their binding to the anion-exchanger. Their uronic acid content and glycosidic linkage composition revealed that the three less acidic AGPs contained from 3 to 7% glucuronic acid, half in terminal non-reducing positions and half in terminal Rhap-(1-->4)-Glc pA-(1-->sequences. The two more acidic AGP-containing fractions contained both glucuronic (6.1 and 13.3%, respectively) and galacturonic (1.9 and 2.3%, respectively) acid in association with 2- and 2,4-linked rhamnose, indicating the presence of AG-rhamnogalacturonan fragments.
Carbohydrate Conformation↗