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A Guha 《Journal of molecular biology》1971,56(1):53-62
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B Mukherji S A Wilhelm A Guha M T Ergin 《Journal of immunology (Baltimore, Md. : 1950)》1986,136(5):1888-1892
The potential existence of down-regulation of cytotoxic immune response against an autologous human melanoma line was investigated as a possible explanation for cytotoxic unresponsiveness against the autologous melanoma cells. The melanoma cell line, PJ-M, was established and lymph node resident lymphocytes (LNL) were isolated from a lymph node which was partially infiltrated with the melanoma cells. Autologous peripheral blood lymphocytes (PBL) were sensitized in in vitro co-culture (IVC) against radiated PJ-M cells in the presence or absence of PJ-M-sensitized LNL and enriched suppressor (OKT8+) or inducer (OKT4+) LNL populations, and were assayed for cytotoxicity in a 4-hr 51Cr-release microcytotoxicity assay. Significant cytotoxic response against PJ-M could be generated in the PBL, but not in the LNL. The addition of sensitized, unfractionated LNL, OKT8+, or OKT4+ LNL populations abrogated cytotoxic response in the PBL against PJ-M. The suppression of cytotoxic response was induced selectively against the PJ-M targets, because IVC of PBL in the presence of the sensitized LNL did not affect the generation of polyclonal cytotoxic alloreactivities, nor did they abrogate the generation of cytotoxic response against allogeneic targets in IVC against the corresponding allogeneic targets. These results suggest the possibility that cytotoxic immune response against the autologous melanoma cells might have been suppressed by the individual's own immunoregulatory circuit. 相似文献
4.
A Guha W Szybalski W Salser E P Geiduschek J F Pulitzer A Bolle 《Journal of molecular biology》1971,59(2):329-349
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E Waxman J B Ross T M Laue A Guha S V Thiruvikraman T C Lin W H Konigsberg Y Nemerson 《Biochemistry》1992,31(16):3998-4003
We find that the isolated, extracellular domain of tissue factor (TF1-218; sTF) exhibits only 4% of the activity of wild-type transmembrane TF (TF1-263) in an assay that measures the conversion of factor X to Xa by the TF:VIIa complex. Further, the activity of sTF is manifest only when vesicles consisting of phosphatidylserine and phosphatidylcholine (30/70 w/w) are present. To determine whether the decreased activity results from weakened affinity of sTF for VIIa, we studied their interaction using equilibrium ultracentrifugation, fluorescence anisotropy, and an activity titration. Ultracentrifugation of the sTF:VIIa complex established a stoichiometry of 1:1 and an upper limit of 1 nM for the equilibrium dissociation constant (Kd). This value is in agreement with titrations of dansyl-D-Phe-L-Phe-Arg chloromethyl ketone active site labeled VIIa (DF-VIIa) with sTF using dansyl fluorescence anisotropy as the observable. Pressure dissociation experiments were used to obtain quantitative values for the binding interaction. These experiments indicate that the Kd for the interaction of sTF with DF-VIIa is 0.59 nM (25 degrees C). This value may be compared to a Kd of 7.3 pM obtained by the same method for the interaction of DF-VIIa with TF1-263 reconstituted into phosphatidylcholine vesicles. The molar volume change of association was found to be 63 and 117 mL mol-1 for the interaction of DF-VIIa with sTF and TF1-263, respectively. These binding data show that the sTF:VIIa complex is quantitatively and qualitatively different from the complex formed by TF1-263 and VIIa. 相似文献
7.
Dominant-negative mutants of platelet-derived growth factor revert the transformed phenotype of human astrocytoma cells. 总被引:7,自引:2,他引:5 下载免费PDF全文
Malignant astrocytoma is the most common primary human brain tumor. Most astrocytomas express a combination of platelet-derived growth factor (PDGF) and PDGF receptor which could close an autocrine loop. It is not known whether these autocrine loops contribute to the transformed phenotype of astrocytoma cells or are incidental to that phenotype. Here we show that dominant-negative mutants of the PDGF ligand break the autocrine loop and revert the phenotype of BALB/c 3T3 cells transformed by the PDGF-A or PDGF-B (c-sis) gene. Then, we show that these mutants are selective in that they do not alter the phenotype of 3T3 cells transformed by an activated Ha-ras or v-src gene or by simian virus 40. Finally, we show that these mutants revert the transformed phenotype of two independent human astrocytoma cell lines. They have no effect on the growth of human medulloblastoma, bladder carcinoma, or colon carcinoma cell lines. These observations are consistent with the view that PDGF autocrine loops contribute to the transformed phenotype of at least some human astrocytomas. 相似文献
8.
Brain glucose bisphosphatase requires inosine monophosphate 总被引:4,自引:0,他引:4
Glucose bisphosphate phosphatase has been partially purified from the cytosol of mouse brain. Enzyme activity required Mg2+ and a heat-stable cofactor. The activator was present in boiled extracts of mouse brain mitochondrial-nuclear fraction, of red blood cells, or of rabbit muscle. The chemical properties of the activator are consistent with its identification as inosine monophosphate (IMP), including its mobility in a high pressure liquid chromatography (HPLC) system capable of resolving all of the biologically important mononucleotides. A large number of other biologically important compounds were not effective, including AMP, cAMP, cGMP, and UMP, GMP, purified by HPLC, (50 or 74 microM), gave a rate about 35% of that obtained with IMP (5 microM). The enzyme was separated completely from phosphoglucomutase and significantly from glucose bisphosphate synthase. The products of the reaction are glucose-P and Pi. Fructose bisphosphate at 500 microM inhibited only 40% in the presence of 20 microM glucose bisphosphate. The activation by IMP follows hyperbolic kinetics with an apparent Ka of 5 microM in the presence of 12 microM glucose bisphosphate. The apparent Km of glucose bisphosphate was 10 microM in the presence of 50 microM IMP. There was no inhibition by 5 or 50 microM AMP or ADP. The possible regulatory importance of glucose bisphosphate in carbohydrate metabolism and the significance of the regulation of the phosphatase by the nucleotide are discussed. 相似文献
9.
Hadley KC Borrelli MJ Lepock JR McLaurin J Croul SE Guha A Chakrabartty A 《Cell stress & chaperones》2011,16(5):549-561
The inability of cells to maintain protein folding homeostasis is implicated in the development of neurodegenerative diseases,
malignant transformation, and aging. We find that multiphoton fluorescence imaging of 1-anilinonaphthalene-8-sulfonate (ANS)
can be used to assess cellular responses to protein misfolding stresses. ANS is relatively nontoxic and enters live cells
and cells or tissues fixed in formalin. In an animal model of Alzheimer’s disease, ANS fluorescence imaging of brain tissue
sections reveals the binding of ANS to fibrillar deposits of amyloid peptide (Aβ) in amyloid plaques and in cerebrovascular
amyloid. ANS imaging also highlights non-amyloid deposits of glial fibrillary acidic protein in brain tumors. Cultured cells
under normal growth conditions possess a number of ANS-binding structures. High levels of ANS fluorescence are associated
with the endoplasmic reticulum (ER), Golgi, and lysosomes—regions of protein folding and degradation. Nuclei are virtually
devoid of ANS binding sites. Additional ANS binding is triggered by hyperthermia, thermal lesioning, proteasome inhibition,
and induction of ER stress. We also use multiphoton imaging of ANS binding to follow the in vivo recovery of cells from protein-damaging
insults over time. We find that ANS fluorescence tracks with the binding of the molecular chaperone Hsp70 in compartments
where Hsp70 is present. ANS highlights the sensitivity of specific cellular targets, including the nucleus and particularly
the nucleolus, to thermal stress and proteasome inhibition. Multiphoton imaging of ANS binding should be a useful probe for
monitoring protein misfolding stress in cells. 相似文献
10.