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31.
Lymphopenia is due to a frameshift mutation in Gimap5 on rat chromosome 4 and is linked to type 1 diabetes in the diabetes prone (DP) BB rat. The hypothesis that bone marrow derived cells confer the lymphopenia phenotype was tested by reciprocal bone marrow transplantation in 40-day-old lethally irradiated diabetes resistant (DR) congenic DR.lyp/lyp (lymphopenia and diabetes) and DR.+/+ (no lymphopenia and no diabetes) rats. In two independent series of transplants, all DR.lyp/lyp rats (n=5 and 4) receiving DR.lyp/lyp bone marrow retained lymphopenia and developed insulitis (5/5 and 4/4) as well as diabetes in some (2/5 and 3/4). Both DR.+/+ and DR.lyp/lyp rats receiving DR.+/+ bone marrow cells as well as DR.+/+ rats receiving DR.lyp/lyp bone marrow cells showed no lymphopenia or diabetes. In accordance with earlier studies in non-congenic BB rats, the DR.+/+ rats receiving DR.lyp/lyp bone marrow cells recapitulated an intermediary phenotype rather than the +/+ or lyp/lyp phenotypes. Our data demonstrate that BBDP rat lymphopenia and diabetes are transferred by bone marrow transplantation to syngeneic DR.lyp/lyp but not DR.+/+ recipients. The intermediary recapitulation of DR.lyp/lyp T cells in recipient DR.+/-/+/- rats suggests that radiation resistant +/-/+/- T cells, the Gimap5 mutation in bone marrow cells, or both may not support the development of lymphopenia. 相似文献
32.
33.
Astrocytes give rise to oligodendrogliomas and astrocytomas after gene transfer of polyoma virus middle T antigen in vivo
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Holland EC Li Y Celestino J Dai C Schaefer L Sawaya RA Fuller GN 《The American journal of pathology》2000,157(3):1031-1037
The cells of origin for oligodendrogliomas and astrocytomas are not known but are presumed to be oligodendrocyte and astrocyte precursors, respectively. In this paper we report the generation of mixed gliomas from in vivo transformation of glial fibrillary acidic protein (GFAP)-positive cells (differentiated astrocytes) with polyoma virus middle T antigen (MTA). MTA is a powerful oncogene that activates a number of signal transduction pathways, including those proposed to be involved in gliomagenesis, and has been shown to induce tumors in many cell types. We have achieved transfer of MTA expression specifically to GFAP(+) cells in vivo using somatic cell gene transfer, and find resultant formation of anaplastic gliomas with mixed astrocytoma and oligodendroglioma morphological features. We conclude that GFAP- expressing astrocytes, with appropriate signaling abnormalities, can serve as the cell of origin for oligodendrogliomas, astrocytomas, or mixed gliomas. 相似文献
34.
Yamaguchi Mamoru Fuller Geraldine Anne Klomkleaw Wuthichai Yamano Shuji Oba Toshiharu 《Journal of muscle research and cell motility》1999,20(4):371-381
The structural changes of the Z-line between small square net (ss) and basket weave (bw) cross-sectional patterns were examined using intact single fibers and mechanically skinned fibers in the passive state to determine if the pattern is related to the sarcomere length (SL) and if the pattern undergoes a reversible transition in low- and high-osmotic medium.Frog single fibers were isolated from the anterior tibial muscle in Ringer's solution. Entirely or partially skinned single fibers were prepared in relaxing solution (also called low-osmotic medium).The high osmotic medium contained 10% polyvinylpyrrolidone (PVP) in relaxing solution.The sarcomere length (SL) of each fiber was measured directly by use of a laser beam or indirectly from electron micrographs with use of a correction factor. The ss and bw forms in cross sections were quantified by analysis of electron micrographs. The results show that the structural change of Z-line occurs around bw 2.3–2.4m ss (n = 25) and bw 3.1–3.2m ss (n = 13) in intact single fibers and skinned fibers, respectively. With the quick freeze-freeze substitution method, an intact single fiber with a SL of 2.35m showed almost 100% of ss form. The structural transition in cross section was also confirmed in four partially skinned fibers, where patterns went from mostly ss form (intact portion) to mostly bw form (skinned portion) at the SL between 2.40 to 3.20m.The reversibility of the change between ss and bw was proved by using low- and high-osmotic medium. The transition and reversion of cross-sectional patterns both occur in the passive state. 相似文献
35.
Experiences of patients with false positive results from colorectal cancer screening. 总被引:1,自引:1,他引:1
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D Mant R Fitzpatrick A Hogg A Fuller A Farmer J Verne J Northover 《The British journal of general practice》1990,40(339):423-425
A survey was conducted to study the experiences of patients with false positive results for colorectal cancer. The study patients were participants in a randomized trial of compliance with different methods of colorectal cancer screening by faecal occult blood testing. Fifty four out of fifty six patients (96.4%) with false positive results agreed to be interviewed. An age and sex matched control group of 112 patients with negative test results was identified --92 (82.1%) returned questionnaires. Thirteen of the patients with false positive results (24.1%) and 19 controls (20.7%) were to some extent distressed by the initial letter inviting them to participate in the screening programme. Thirty seven of the patients with false positive results (68.5%) felt some degree of distress at the initial positive test result and 19 (35.2%) some distress because of delays experienced in the process of being screened. Ten false positive patients had colonoscopy and the median waiting time for this procedure was 10 days--half of the patients found this wait distressing. Nevertheless, 53 of the patients with false positive results (98.1%) felt that it had been worthwhile to have had the test. Generally, colorectal screening was as acceptable to the patients who experienced false positive results as to those with negative results. 相似文献
36.
Fuller JR Pitzer JE Godwin U Albertino M Machon BD Kearse KP McConnell TJ 《Developmental and comparative immunology》2004,28(6):603-617
Folding and assembly of MHC molecules in mammals occurs in the endoplasmic reticulum (ER), but has not been studied in teleosts. Calnexin (CNX) is an ER chaperone that associates with glycoproteins bearing a monoglucosylated N-linked oligosaccharide side chain. Here we report the first identification and characterization of a full-length CNX cDNA clone in a teleost, and the association of the CNX chaperone with MHC class II in a channel catfish T cell line. The 1.8 kb CNX clone encodes a protein of 607 amino acids that is 72% identical to the consensus sequence of mammalian CNXs. The association of CNX with class II is of particular interest because the native MHC class II alpha chain of Ictalurus punctatus does not bear any N-linked oligosaccharide consensus glycosylation sequences. Thus the assembly of class II molecules in the catfish probably proceeds via different steps than occurs in mammals. 相似文献
37.
Yide Jin Laphalle Fuller Manuel Carreno Keith Zucker David Roth Violet Esquenazi Theodore Karatzas Sidney J. Swanson III Andreas G. Tzakis Joshua Miller 《Journal of clinical immunology》1997,17(2):140-153
Liver infiltrating lymphocytes (LIL) were isolated from HCV-positive (+) and HCV-negative (–) end-stage livers. Phenotypic analysis and functional studies using proliferative and lymphocytotoxic assays were performed with the isolated LIL. Two CD3+ lymphocyte populations were found in LIL using FITC anti-CD3 monoclonal antibodies (mAb). One was a bright fluorescence intensity population (as in PBL), and the other dim. We calculated the number of FITC-anti-CD3 mAbs bound per lymphocyte on PBL and LIL and found 80,040 ± 4628 and 39,615 ± 3932, respectively. Therefore, HCV+ and HCV– patient PBL contained approximately twice the number of CD3 molecules per cell than patient CD3+ LIL. LIL also contained approximately a threefold higher concentration of TCR+, CD4–CD8–, and CD56,16 (NK) cells than the patient PBL. Thus, a major subset of LIL is phenotypically similar to mouse NK1.1+ intermediate T cells. LIL freshly isolated from HCV+ livers exhibited weak CTL activity against EBV- or Con A-transformed lymphoblast targets infected with vaccinia–HCV recombinant virus (rHCV) or primary hepatocyte cultured cells. However, after in vitro coculture of LIL with rHCV, these cells developed a strong cytotoxicity for the above targets. In contrast, LIL from HCV– livers were not cytotoxic against the same targets. Histochemical studies (in situ) demonstrated that these hepatocytes express CD95, and stains demonstrated apoptosis. The HCV+ hepatocytes also express class I MHC molecules and ICAM-1. The addition of mAb specific for these adhesion molecules inhibited CML activity. Short-term cultured hepatocytes (targets) from HCV+ and HCV– patients produced low levels of cytokines IL-1, IL-2, IL-6, TNF, and IFN- but a high level of IL-8. It is speculated that LIL expressing reduced numbers of CD3 molecules may even function as immune regulators as proposed for intermediate T cells in mice. 相似文献
38.
Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes 总被引:17,自引:8,他引:17
Campuzano V; Montermini L; Lutz Y; Cova L; Hindelang C; Jiralerspong S; Trottier Y; Kish SJ; Faucheux B; Trouillas P; Authier FJ; Durr A; Mandel JL; Vescovi A; Pandolfo M; Koenig M 《Human molecular genetics》1997,6(11):1771-1780
Friedreich ataxia is a progressive neurodegenerative disorder caused by
loss of function mutations in the frataxin gene. In order to unravel
frataxin function we developed monoclonal antibodies raised against
different regions of the protein. These antibodies detect a processed 18
kDa protein in various human and mouse tissues and cell lines that is
severely reduced in Friedreich ataxia patients. By immunocytofluorescence
and immunocytoelectron microscopy we show that frataxin is located in
mitochondria, associated with the mitochondrial membranes and crests.
Analysis of cellular localization of various truncated forms of frataxin
expressed in cultured cells and evidence of removal of an N-terminal
epitope during protein maturation demonstrated that the mitochondrial
targetting sequence is encoded by the first 20 amino acids. Given the
shared clinical features between Friedreich ataxia, vitamin E deficiency
and some mitochondriopathies, our data suggest that a reduction in frataxin
results in oxidative damage.
相似文献
39.
Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro 总被引:2,自引:0,他引:2
The present study was designed to ascertain whether the negative effects on
reproductive potential of post-ovulatory ageing in vitro of oocytes can be
prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were
aged in vitro for 12 h prior to insemination in the presence of varying
concentrations of L-ascorbic acid, 6-methoxy-
2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine
dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta-
mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was
associated with lower fertilization rate, higher proportion of concepti
exhibiting cellular fragmentation at 24 h post-insemination and lower
percentage of concepti reaching the blastocyst stage. Ascorbic acid, Trolox
and EDTA had no effect on cellular fragmentation or potential of oocytes
for development. However, the probability of an oocyte reaching the
blastocyst stage was decreased (P < or = or = 0.05) in oocytes incubated
in the presence of L-cystine (50 and 500 microM) and beta-mercaptoethanol
(5, 50 and 500 microM) when compared to control aged oocytes.
Age-associated cellular fragmentation at 24 h post-insemination was
partially prevented (P < or = 0.05) by incubating oocytes in the
presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM)
increased (P < or = 0.05) fertilization rate and number of cells at 81 h
post-insemination to levels similar to those exhibited by control oocytes.
Furthermore, both age-associated fragmentation at 24 h post-insemination (P
< or = 0.05) and decreased potential of oocytes for development to the
blastocyst stage (P < or = 0.05) were prevented, at least in part, by
culturing oocytes in the presence of DTT (50 microM). Although the
mechanism by which DTT exerts its beneficial effects on aged oocytes
remains to be elucidated, it may protect oocytes by preventing oxidation of
free thiol groups and/or altering a redox-independent signalling pathway
that mediates cellular fragmentation and death.
相似文献
40.
It is well recognized that the ability to cryopreserve unfertilizedhuman oocytes would make a significant contribution to infertilitytreatment. However, despite considerable interest, very fewsuccessful pregnancies have arisen from cryopreserved oocytesafter thawing, insemination and transfer of the subsequent embryo.The reasons for this lack of progress may well result from adearth of information on how the various biophysical changesduring a cryopreservation regimen affect human oocyte function.Recently, fundamental studies on the effects of cooling, membranepermeability, cryoprotectant addition and ice formation havebeen performed on human oocytes by a number of groups, and theseform the basis of the current review. It is likely that successfulhuman oocyte cryopreservation will only follow once these factorsare fully understood, but the existing base of knowledge shouldprovide a platform for further improvements in the techniquescurrently employed. 相似文献