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151.
Activation of opioid receptors in the periphery and centrally in the brain results in inhibition of gastric and other vagally mediated functions. The aim of this study was to examine the role of the endogenous opioid agonist endomorphin 1 (EM-1) in regulating synaptic transmission within the nucleus tractus solitarius (NTS), an integration site for autonomic functions. We performed whole cell patch-clamp recordings from coronal brain slices of the rat medulla. A subset of the neurons studied was prelabeled with a stomach injection of the transsynaptic retrograde virus expressing EGFP, PRV-152. Solitary tract stimulation resulted in constant latency excitatory postsynaptic currents (EPSCs) that were decreased in amplitude by EM-1 (0.01-10 microM). The paired-pulse ratio was increased with little change in input resistance, suggesting a presynaptic mechanism. Spontaneous EPSCs were decreased in both frequency and amplitude by EM-1, and miniature EPSCs were reduced in frequency but not amplitude, suggesting a presynaptic mechanism for the effect. Spontaneous inhibitory postsynaptic currents (IPSCs) were also reduced in frequency by EM-1, but the effect was blocked by TTX, suggesting activity at receptors on the somata of local inhibitory neurons. Synaptic input arising from local NTS neurons, which were activated by focal photolysis of caged glutamate, was inhibited by EM-1. The actions of EM-1 were similar to those of D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) and were blocked by naltrexone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP). These results suggest that EM-1 acts at mu-opioid receptors to modulate viscerosensory input and specific components of local synaptic circuitry in the NTS. 相似文献
152.
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154.
Barbara A Malynn Albert C Shaw Faith Young Valerie Stewart Frederick W Alt 《Molecular immunology》2002,38(7):547-556
Early stages of B cell development are dependent on the expression of a pre-B cell receptor (BCR), composed of a mu heavy chain (HC) in association with surrogate light chain (SLC) proteins and the signaling molecules, Igalpha and Igbeta. During the formation of the variable region of the mu chain by somatic gene rearrangement, a truncated form of the mu protein (called Dmu) is sometimes produced by the rearrangement of a D(H) segment to a J(H) segment using one of three reading frames (designated rf2). When a Dmu protein is formed, subsequent B cell development is blocked by down-regulation of further HC rearrangements, so that a full-length muHC cannot be formed. In this study, we demonstrate that in recombinase activating gene (RAG)-2-deficient B220(+) CD43(+) pro-B cells in which B lymphopoiesis has been arrested at fraction C, transgenic expression of Dmu promoted partial developmental progression to fraction C', but was unable to mediate the pro-B to pre-B cell transition to fraction D effected by full-length muHC protein. These data suggest that the intracellular signaling pathways engaged by the Dmu pre-BCR are insufficient to facilitate the expansion and/or survival of pre-B cells, and are distinct from those engaged by the pre-BCR-containing full-length muHC. 相似文献
155.
P Vandenabeele B Jayaram R Devos A Shaw W Fiers 《European journal of immunology》1988,18(7):1027-1031
The Epstein-Barr virus-transformed B cell line RPMI 1788 constitutively produces autocrine growth factors with molecular masses of 17 kDa, 24 kDa and 35 kDa. All three molecular forms were completely neutralized with anti-interleukin (IL) 1 alpha antiserum. Although IL 1 alpha and IL 1 beta mRNA were both equally detectable by Northern blotting, no IL 1 beta activity was found in partially purified RPMI 1788 supernatant. The growth of low density-seeded RPMI 1788 cells is specifically dependent on the presence of either IL 1 alpha or IL 1 beta. Since no other cytokine was found to be capable of sustaining proliferation, this cell line is suitable for the identification and quantification of IL 1, even in the presence of other cytokines. 相似文献
156.
Kenneth Micklethwaite Anna Hansen Aaron Foster Elizabeth Snape Vicki Antonenas Mary Sartor Peter Shaw Ken Bradstock David Gottlieb 《Biology of blood and marrow transplantation》2007,13(6):707-714
Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation. 相似文献
157.
Tetanus toxin (about 20 mouse LD50) injected into the ventral hippocampus of rats leads to brief seizures occurring intermittently over a period of weeks. Toxin injection leads to the appearance of activated microglia (detected with OX42 immunohistochemistry) in the hippocampus. After 7-14 days, many activated microglia are visible in CA1 area of dorsal hippocampus aligned with the pyramidal cell dendrites and having the morphology characteristic of 'rod cells'. Extensive cell loss is found in dorsal CA1, but not at the injection site, in about one third of injected rats. 相似文献
158.
Involvement of 2p23 in pulmonary inflammatory pseudotumors 总被引:2,自引:0,他引:2
Pulmonary inflammatory pseudotumors (IP) are rare mesenchymal proliferations that have a polymorphic histology and an unpredictable biologic behavior. The histologic spectrum of IP has led to uncertainty as to whether this tumor has a reactive or neoplastic pathogenesis. Reports of extrapulmonary IP have identified clonal chromosomal aberrations involving 2p23 in the region of the ALK gene. Using fluorescence in situ hybridization with a probe flanking the ALK gene at 2p23 and immunostaining for the ALK gene product, we studied formalin-fixed, paraffin-embedded tissues of pulmonary IP and found a subset (33%) with 2p23 aberrations. We suggest that chromosomal rearrangements and ALK immunostaining may be helpful in the diagnosis of a group of pulmonary IP and should be investigated as a potential tool for predicting their future biologic behavior. An association with anaplastic large-cell lymphoma was also observed. HUM PATHOL 32:428-433. 相似文献
159.
1. A small volume of artificial sea water containing 300 nM tetrodotoxin (TTX) was applied successively to seven lobster nerve trunks and the cumulative uptake of toxin investigated by bio-assay.2. Light and electron microscopy indicated that the nerve trunks had a total axonal area of 0·7 × 104 cm2/g.3. Sodium analysis gave a sodium space for the nerve trunks of 30%.4. The amount of toxin taken up by the cells in 1 g of nerve is less than 1·6 × 10-11 moles.5. It is argued that there are probably fewer than 13 sodium channels/μ2 axon in lobster nerve. 相似文献
160.
Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs 总被引:8,自引:2,他引:8
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Park SS Stankiewicz P Bi W Shaw C Lehoczky J Dewar K Birren B Lupski JR 《Genome research》2002,12(5):729-738
An approximately 4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is located between them. SMS-REPs are believed to mediate nonallelic homologous recombination, resulting in both SMS deletions and reciprocal duplications. To delineate the genomic structure and evolutionary origin of SMS-REPs, we constructed a bacterial artificial chromosome/P1 artificial chromosome contig spanning the entire SMS region, including the SMS-REPs, determined its genomic sequence, and used fluorescence in situ hybridization to study the evolution of SMS-REP in several primate species. Our analysis shows that both the proximal SMS-REP (approximately 256 kb) and the distal copy (approximately 176 kb) are located in the same orientation and derived from a progenitor copy, whereas the middle SMS-REP (approximately 241 kb) is inverted and appears to have been derived from the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were duplicated after the divergence of New World monkeys from pre-monkeys approximately 40-65 million years ago. Our findings potentially explain why the vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and distal SMS-REPs and further support previous observations that higher-order genomic architecture involving LCRs arose recently during primate speciation and may predispose the human genome to both meiotic and mitotic rearrangements. 相似文献