Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were trained to asymptotic performance in an 8-arm radial maze. They then received chronic intraventricular infusion of either artificial CSF or the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5- phosphonopentanoic acid (AP5), at a concentration (30 mM) that has been shown previously to prevent the induction of long-term potentiation in the dentate gyrus of the hippocampus in vivo. Subsequently the rats received another 9 trials in the maze in a quasi-random order, 3 uninterrupted trials, and another 6 trials each with mid-trial delays of 5, 20 or 60 min during which the animals were placed in their home cage. The mean number of errors for the AP5 rats did not differ significantly from that of the controls in the uninterrupted trials throughout the experiment, nor did it differ from that of the controls in any of the 3 delayed trials when these were first introduced. However, the control animals performed better at the longer delays when these were introduced for the second time, whilst there was no such improvement (but rather a deterioration) for the AP5 animals. The impairment of performance in the AP5 rats during the second block of delayed trials was significant, and independent of the length of the delay. These results show that NMDA receptor blockade does not impair working memory in the radial maze per se, but that it does prevent an improvement of working memory persistence with further training.
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PMID:Effects of intraventricular infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist AP5 on spatial memory of rats in a radial arm maze. 135 Apr 49

The behavioral consequences of the central administration of corticotropin releasing hormone (CRH) in rhesus monkeys was determined using food-maintained behavior. Acute doses of CRH (0.003 ng/kg-10 micrograms/kg, i.c.v.), decreased responding for food in a dose- and time-related manner. With intermediate doses, responding occurred at a high rate until food was delivered, and then abruptly ceased for several minutes. Previous studies have attributed similar effects to the noxious properties of certain drugs. Acute doses had no effect on home cage food consumption, body weight, or responding for food on subsequent days. When CRH was given repeatedly for several days, its behavioral suppressant effects increased. Home cage food intake, body weight, and subsequent responding for food decreased for up to 6 weeks before returning to normal. These results suggest that sustained elevations in central levels of CRH can result in a sensitization to its anorexigenic effects, an effect that has not been reported in other species. Because hyperaroused clinical states such as depression and anorexia nervosa are characterized biochemically by hypercortisolism and elevated CRH in CSF, these anorexigenic effects may corroborate a potential role for CRH in affective disorders.
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PMID:Corticotropin releasing hormone produces profound anorexigenic effects in the rhesus monkey. 204 89

Two groups of vervet monkeys were fed, on alternate days, either before or after a morning observation period. This enabled us to determine changes in behavior when the animals were fed a nutritionally balanced breakfast of monkey chow. Feeding did not alter the proportion of behaviors that were social or non-social, but had a marked effect on individual behaviors. Feeding increased active behaviors among the adult animals except for the vervets who were lowest in the social hierarchy in each cage. For some of the individual behaviors that were altered by feeding, the changes were most marked early on in the observation period, when the animals were still feeding. Other behavioral changes were seen only later in the observation period, a time course consistent with a food-mediated change in brain biochemistry. A parallel biochemical experiment showed that feeding decreased the levels of tryptophan and 5-hydroxyindoleacetic acid in the CSF. Our data indicate that feeding can influence both brain biochemistry and behavior. The behavioral changes may be influenced by social and psychological factors as well as changes in brain biochemistry.
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PMID:The effect of breakfast on social behavior and brain amine metabolism in vervet monkeys. 335 16

Studies on the influence of substances on the central nervous system and on the function of the blood-CSF-barrier made long-term cannulation of the CSF compartment interesting. This study was to test, whether a permanent CSF-drainage from any point of the subarachnoid space was possible with modified "tissue cages" (Guyton 1963). For that purpose a steel wire cage and a teflon cage were implanted subarachnoidally into beagle dogs. The two cages stopped draining on the second and on the third day respectively. Histological examination showed, that, because of the strong reaction of animal tissue to implanted material, direct cannulation of the CSF compartment does not seem feasible. In the second part the "Manuilov-system" was modified. An indwelling guiding tube was implanted and fixed with a horseshoe shaped plate to the occipital bone. Puncture can be made on the awake dog without local anaesthetic and produces samples of 1.5 to 2.0 ml CSF for up to 30 days without complications.
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PMID:Problems of long-term cannulation of cisterna magna and subarachnoid space in the conscious dog.--Technical note--. 714 4

Strain differences in temperament and physiology have been reported for several animal species, but nonhuman primates have not been well studied in this regard. We assessed behavioral and physiology in Chinese-Indian hybrid (n = 13) and Indian-origin (n = 29) nursery-reared rhesus monkey infants. Previous data indicate that Chinese-origin and Chinese-Indian hybrid rhesus exhibit more aggression directed toward humans and conspecifics and are more irritable in response to neonatal assessment procedures than are Indian-derived rhesus. In addition, in rhesus adults, low levels of cerebrospinal fluid 5-HIAA have been correlated with impulsivity, aggressive behavior, and diminished social competence. We therefore hypothesized that hybrid infants would exhibit more behavioral and adrenocortical reactivity in the home cage and during social separations, would be less sociable in their peer groups, and would exhibit lower CSF 5-HIAA levels than Indian-derived monkeys. Blood and cerebrospinal fluid samples were obtained on Days, 14, 30, 60, 90, 120, and 150 of life, and prior to and during social separations at 6 months of age. Behavioral observations were conducted in the home cage and during the separation condition. No differences in behavior were observed between hybrid and Indian-derived animals in the home cage. Indian-derived and hybrid infants exhibited diverging patterns of behavioral reactivity across the 4 weeks of the repetitive social-separation procedure, and during reunion periods. Although plasma cortisol levels were sensitive to the testing conditions, no group differences were observed. CSF 5-HIAA declined over time for all monkeys, and hybrid animals exhibited significantly lower 5-HIAA levels than Indian monkeys beginning at 6 months of age. These findings are consistent with the known behavioral and physiological characteristics of Chinese-origin adult rhesus.
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PMID:Behavioral and physiological characteristics of Indian and Chinese-Indian hybrid rhesus macaque infants. 922 16

The specific aim of this study was to examine the prophylactic as well as the therapeutic efficacies of irradiated mouse CT26 colon cancer cells, infected with recombinant adenoviruses harboring cDNAs specific for granulocyte macrophage-colony-stimulating factor (GM-CSF), interferon (IFN-gamma) and monocyte chemotactic protein1 (MCP-1). Results showed that tumor cells secrete the respective cytokines for several days after infection and subsequent irradiation. Vaccination with irradiated GM-CSF-secreting CT26 cells protected 90% of syngeneic mice challenged with live parental cells. On the other hand, vaccination with irradiated IFNgamma or MCP-1-secreting CT26 cells totally failed to protect mice from tumor development after challenge with parental cells. None of the tumor-free mice initially vaccinated with irradiated GM-CSF-producing CT26 cells developed tumor upon repeated challenge with parental cells during the entire observation period. The establishment of specific and long-lasting antitumor immunity following vaccination with GM-CSF-producing tumor cells requires the simultaneous presence of GM-CSF and tumor antigen at the vaccine site. Depletion of CD8+ cells, but not CD4+ cells, blocked the vaccine efficacy of GM-CSF-producing tumor cells. Subcutaneous injection of irradiated GM-CSF-producing CT26 cells also effectively prevented the growth of a small load of parental tumor that was implanted 3 days earlier or the development of metastatic foci in the lung from intravenously injected parental cells either 7 days before or 3 days after vaccination. Our data thus show that, in these experimental tumor models, subcutaneous injection of irradiated tumor cells adenovirally, transduced with the GM-CSF gene leads not only to prevention of growth of subsequently implanted tumor but also to elimination of pre-existing and metastatic tumors.
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PMID:Irradiated tumor cells adenovirally engineered to secrete granulocyte/macrophage-colony-stimulating factor establish antitumor immunity and eliminate pre-existing tumors in syngeneic mice. 976 15

Suicide gene therapy has been studied intensively for the treatment of cancer. A limited antitumoral effect was obtained by intratumoral injection of adenovirus harboring Escherichia coli cytosine deaminase gene (AdCD) in tumor-bearing mice followed by continuous administration of 5-fluorocytosine (5FC). To address the drawbacks of the limited potential for the induction of antitumoral immunity by CD suicide gene therapy, we hypothesized that antigen-presenting cells (APCs) might contribute to the efficient induction of an antitumoral immune response in tumor-bearing mice undergoing suicide gene therapy. We preinjected the mice with murine stem cell factor (SCF)-encoding adenovirus (AdSCF) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-encoding adenovirus (AdGM-CSF); after 7 days, the mice were inoculated with CT26 colon adenocarcinoma. AdCD was injected intratumorally into tumor-bearing mice followed by 5FC administration. The results showed that AdSCF/AdGM-CSF treatment could increase the number, surface molecule expression, and function of APCs efficiently. A more significant growth inhibition of established tumors and a prolongation of the survival period were observed in tumor-bearing mice after AdSCF/AdGM-CSF pretreatment in combination with AdCD/5FC therapy when compared with mice treated with AdSCF or AdGM-CSF in combination with AdCD/5FC, or AdCD/5FC alone (P < .01). Cytotoxic T-lymphocyte activity was induced efficiently after the combined therapy, and mRNA of tumor necrosis factor-alpha, interleukin-4, interferon-gamma, and interleukin-2 was present in the tumor mass after combined therapy, suggesting that a more potent antitumoral response was induced by enhanced APCs. Our results demonstrated that AdSCF/AdGM-CSF pretreatment could activate APCs, and that these APCs could present the tumor antigens released from AdCD/5FC-killed tumor cells and activate the antitumoral response of the host, thus increasing the therapeutic efficiency of suicide gene therapy.
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PMID:Enhanced antitumoral effect of adenovirus-mediated cytosine deaminase gene therapy by induction of antigen-presenting cells through stem cell factor/granulocyte-macrophage colony-stimulating factor gene transfer. 1077 Jun 25

Anti-HER2/neu therapy of human HER2/neu-expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu IgG3 fusion protein containing GM-CSF. Anti-HER2/neu IgG3-(GM-CSF) expressed in myeloma cells was correctly assembled and secreted. It was able to target HER2/neu-expressing cells and to support growth of a GM-CSF-dependent murine myeloid cell line, FDC-P1. The Ab fusion protein activated J774.2 macrophage cells so that they exhibit an enhanced cytotoxic activity and was comparable to the parental Ab in its ability to effect Ab-dependent cellular cytotoxicity-mediated tumor cell lysis. Pharmacokinetic studies showed that anti-HER2/neu IgG3-(GM-CSF) is stable in the blood. Interestingly, the half-life of anti-HER2/neu IgG3-(GM-CSF) depended on the injected dose with longer in vivo persistence observed at higher doses. Biodistribution studies showed that anti-HER2/neu IgG3-(GM-CSF) is mainly localized in the spleen. In addition, anti-HER2/neu IgG3-(GM-CSF) was able to target the HER2/neu-expressing murine tumor CT26-HER2/neu and enhance the immune response against the targeted Ag HER2/neu. Anti-HER2/neu IgG3-(GM-CSF) is able to enhance both Th1- and Th2-mediated immune responses and treatment with this Ab fusion protein resulted in significant retardation in the growth of s.c. CT26-HER2/neu tumors. Our results suggest that anti-HER2/neu IgG3-(GM-CSF) fusion protein is useful in the treatment of HER2/neu-expressing tumors.
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PMID:Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity. 1104 42

Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage stimulating factor (GM-CSF) are currently licensed for use in cancer patients and play a significant role in the management of anemia and neutropenia following myeloblative chemotherapy. EPO was the first recombinant hematopoietic growth factor to be used clinically after a number of clinical trials which demonstrated its effectiveness in treating mild to moderate cancer-associated anemia with or without concomitant chemotherapy (particulary cisplatin). An extensive research has been made for the improvement of the quality of life with EPO therapy, however, when formally assessed, variable effects of this important treatment have been observed. Recently, EPO has been shown to significantly accelerate hematopoietic reconstitution after peripheral blood stem cell transplantation (PBSCT) resulting in reduced infection rates. Both, G-CSF and GM-CSF have been shown, in numerous trials, to shorten the period of chemotherapy-induced neutropenia, with reduction in attendant morbidity and to mobilize PBSC. In addition, administration of both cytokines after PBSCT significantly reduced the use of antibiotics and duration of hospitalization suggesting an economic benefit. The narrower therapeutic window of GM-CSF at higher doses accounts for the fact that it is used much less frequently than G-CSF. To date, none of the growth factors used clinically has been shown to stimulate thrombopoiesis. Although thrombopoietin (TPO) has been found to induce megakaryocyte differentiation in vitro, it is unlikely to enter routine clinical use for treatment of post-chemotherapy thrombocytopenia, since results of clinical trials are not very encouraging, mainly because TPO is difficult to schedule and platelet aggregation may occur. Recently, innovative chimeric growth factor receptor agonists have been synthesized. Synthokine (SC-55494) (a high-affinity human IL-3 receptor ligand analog), myelopoietin (MPO) (activates human IL-3 and G-CSF receptors) and promegapoietin (PMP) (stimulates the human IL-3 and c-mpl receptors) were found to be multilineage hematopoietic growth factors and are currently undergoing clinical trials. Preliminary results suggest that these compounds may have a major impact on the management of myeloablative chemotherapy because of their ability to enhance platelet recovery in addition to their neutrophil restorative activity.
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PMID:Human hematopoietic growth factors: old lessons and new perspectives. 1132 88

Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-gamma, but not IL-4 cytokine production. Depletion of CD8(+) T cells from regressor splenocytes before in vitro stimulation with the relevant peptide abolished their cytolytic activity, while depletion of CD4(+) T cells only partially inhibited CTL generation. Tumor regression induced by DISC/mGM-CSF virus immunotherapy provides a unique model for evaluating the immune mechanism(s) involved in tumor rejection, upon which tumor immunotherapy regimes may be based.
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PMID:Tumor regression induced by intratumor therapy with a disabled infectious single cycle (DISC) herpes simplex virus (HSV) vector, DISC/HSV/murine granulocyte-macrophage colony-stimulating factor, correlates with antigen-specific adaptive immunity. 1190 13


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