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141.
Laura Chiarantini Luigia Rossi Alessandra Fraternale Mauro Magnani 《Molecular and cellular biochemistry》1995,144(1):53-59
Human and murine blood cells treated with ZnCl2 and bis(sulfosuccinimidyl)suberate (BS3) (a cross linking agent) undergo band 3 clustering and binding of hemoglobin to red blood cell membrane proteins. These clusters induce autologous IgG binding and complement fixation, thus favouring the phagocytosis of ZnCl2/BS3 treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by changing the ZnCl2 concentration in the 0.1–1.0 mM range thus providing an effective way to affect blood cell recognition by macrophages. In fact, murine erythrocytes treated with increasing ZnCl2 concentrations have proportionally reduced survivals when reinjected into the animal. Furthermore, the organ sequestration of ZnCl2/BS3 treated cells strongly resembles the typical distribution of the senescent cells. Since the ZnCl2/BS3 treatment can also be performed on red blood cells loaded with drugs or other substances, this procedure is an effective drug-targeting system to be used for the delivery of molecules to peritoneal, liver and spleen macrophages. 相似文献
142.
Paul G. Braunschweiger Vathsala S. Basrur Dayna Cameron Laura Sharpe Octavio Santos James P. Perras Bernd-Uwe Sevin Arnold M. Markoe 《Biotherapy》1997,10(2):129-137
The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1α) was studied in cultures of SCC-7 tumor cells with and without
tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1α in SCC-7 solid
tumors. Neither IL-1α nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1α had no direct effect
on tumor cell growthin vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90=6.0 μM), but, the addition of IL-1α (500–2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor
macrophages increased cell killing (IC90=3.1 μM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1α. The modulation of cisPlatin
cytotoxicity by IL-1α exhibited a biphasic dose response that paralleled the IL-1α dose dependent release of H2O2by resident tumor macrophages. Further, IL-1α modification of cisPlatin cytotoxicity was prompt and inhibited by catalase.
CisPlatin and exogenous H2O2 (50 μM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response.
Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1α treatment for 24 hrs, before cisPlatin, produced
drug resistance (IC90=11.1 μM). Our study shows that IL-1α can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity
in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explanation for the synergistic antitumor
activity of cisPlatin and IL-1αin vivo. 相似文献
143.
144.
Stereoselectivity of the Chinese hamster ovary cell sialidase: sialoside hydrolysis with overall retention of configuration 总被引:1,自引:1,他引:0
The stereochemical course of enzymatic hydrolysis by the solublesialidase from Chinese hamster ovary cells, expressed as a recombinantprotein in insect Sf9 cells, was determined using proton nuclearmagnetic resonance spectroscopy. 4-Methyl umbelliferyl-N-acetylneuraminic acid was employed as substrate, and the stereoselectivityof the enzyme catalysis was ascertained by monitoring the H3axial and equatorial protons of the sialic acid product overthe reaction course. At both high (3 U) and low concentrations(1 U) of the enzyme, the alpha anomer of the sialic acid wasclearly observed as the initial reaction product. The correspondingbeta anomer of sialic acid appeared much later in the reaction,arising from mutarotation of the alpha anomer. Similar studieswere also carried out using the Salmonella typhimurium LT 2sialidase, a protein of similar size and substrate specificity.Both enzymes apparently cleave the alpha linked sialoside substratewith retention of configuration. Based on the observations ofa wide variety of other glycohydrolytic enzymes that have showna strong correlation of the stereoselectivity of catalysis withactive site topology (Gebler et al, J. Biol. Chem. 267, 1255912561,1992), the results obtained here suggest that the microbialand mammalian sialidases have a homologous active site architectureeven though the molecules do not share significant primary sequencesimilarities. sialidase NMR enzyme mechanism Chinese hamster 相似文献
145.
The selectins are a family of proteins that mediate leukocytetethering and rolling along the vascular endothelium. E-, P-,and L-selectin recognize various derivatives of the Lewisa andLewisx trisaccharides. The distribution of negative chargeson the Lewisa and Lewisx oligosaccharides appears to be an importantfactor in their binding by the selectins. Previous work exploringthis electrostatic dependence found that a series of syntheticanionic trisaccharides, 3'-sulfo, 3'-phospho, 6'-sulfo, and3',6'-disulfo Lewisa. (Glc), exhibited differing selectin inhibitoryefficacies. To explore the possibility that these differencesarise from conformational differences between the sugars, thesolution structures of these trisaccharides were determinedusing NMR and molecular dynamics simulations. Interproton distancesand interglycosidic torsion angles were determined at 37°Cusing NOESY buildup curves and 1D LRJ experiments, respectively.Data from both experiments agreed well with predictions madefrom 2000 picosecond unrestrained molecular dynamics simulations.We found that 3'-sulfation did not alter the core Lewisa conformation,a finding that reaffirms the results of previous study. In addition,we found that sulfation at the 6' position also leaves the trisaccharideconformation unperturbed. This is significant because the proximityof the 6'-sulfate group to the fucose ring might have alteredthe canonical Lewisa structure. The disulfate exhibited greaterflexibility than the other derivatives in dynamics simulations,but not so much as to affect NOE and heteronuclear couplingconstant measurements. Taken together, our findings supportthe use of Lewisa as a template onto which charged groups maybe added without significantly altering the trisaccharide'sstructure. oligosaccharides molecular dynamics simulations NMR sulfated Lewisa phosphorylated Lewisa 相似文献
146.
Michael Garrick Donna Scott Susannah Walpole Eric Finkelstein Joy Whitbred Sandeep Chopra Lalitha Trivikram David Mayes Daphne Rhodes Kimberly Cabbagestalk Rahmi Oklu Adnan Sadiq Brett Mascia James Hoke Laura Garrick 《Biometals》1997,10(2):65-76
Belgrade rats inherit microcytic, hypochromic anemia as an autosomalrecessive trait (gene symbol b). Erythrocytes and tissue are iron deficientin the face of elevated TIBC (total iron binding capacity) and percent ironsaturation; iron injections increased the number of erythrocytes but theirappearance remained abnormal. We have investigated iron supplements toimprove husbandry of b/b rats and to learn more about the underlying defectand its tissue distribution. Weekly IM (intramuscular) injections ofiron–dextran (Imferon at 30 mg kg) improved the anemia but did not alter thered cell morphology. Certain diets also improved the health of b/b rats whencompared to standard rat chows by the criteria of weight, survival toadulthood, hematology and reproduction. The critical nutritional factorturned out to be iron bioavailability, with ferrous iron added to the dietimproving the health of Belgrade rats without affecting the underlyingerythroid defect. Tissue iron measurements after dietary or parenteralsupplementation confirmed the iron deficient status of untreated b/b rats andestablished that dietary ferrous iron partially relieved this deficiency,with injections leading to greater amounts of tissue iron. Serum iron andTIBC were also found to be elevated in untreated b/b rats, with dietarysupplementation decreasing but not eliminating the elevation in TIBC. Thesestudies indicate that iron supplements can improve the health of b/b ratswithout altering the underlying defect and also suggest that the mutationcould alter iron uptake in the GI (gastrointestinal) tract. 相似文献
147.
Three strains of Saccharomyces cerevisiae, SC-1, DBVPG 6173 and DBVPG 6037, were studied for vanadate resistance in complex Sabouraud medium since they did not thrive in different minimal media (yeast nitrogen base with and without amino acids). The strain SC-1 was resistant up to 16 mm of vanadate, whereas the strains DBVPG 6173 and DBVPG 6037 were inhibited by 8 mm and 4 mm vanadate, respectively. The vanadate resistance in strain SC-1 was constitutive and due to the reduction of this oxyanion to vanadyl, which was detected by EPR spectroscopy and visible spectroscopy. The transformation of vanadate to vanadyl took place during the exponential growth phase; 10 mm of vanadate was reduced to vanadyl outside the cells since the oxyanion was not detected in the cell biomass and only a negligible concentration of vanadyl (25 nmoles mg cells dry weight) was found in the biomass. The other two vanadate-sensitive yeast strains only accumulated vanadate and did not reduce the oxyanion to vanadyl. 相似文献
148.
Dictyostelium RasG Is Required for Normal Motility and Cytokinesis, But Not Growth 总被引:1,自引:0,他引:1
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Richard I. Tuxworth Janet L. Cheetham Laura M. Machesky George B. Spiegelmann Gerald Weeks Robert H. Insall 《The Journal of cell biology》1997,138(3):605-614
RasG is the most abundant Ras protein in growing Dictyostelium cells and the closest relative of mammalian Ras proteins. We have generated null mutants in which expression of RasG is completely abolished. Unexpectedly, RasG− cells are able to grow at nearly wild-type rates. However, they exhibit defective cell movement and a wide range of defects in the control of the actin cytoskeleton, including a loss of cell polarity, absence of normal lamellipodia, formation of unusual small, punctate polymerized actin structures, and a large number of abnormally long filopodia. Despite their lack of polarity and abnormal cytoskeleton, mutant cells perform normal chemotaxis. However, rasG− cells are unable to perform normal cytokinesis, becoming multinucleate when grown in suspension culture. Taken together, these data suggest a principal role for RasG in coordination of cell movement and control of the cytoskeleton. 相似文献
149.
†Alessandro P. Burlina †Vanni Ferrari ‡Laura Facci ‡Stephen D. Skaper § Alberto B. Burlina 《Journal of neurochemistry》1997,69(3):1314-1317
Abstract: Mast cells play a central role in both immediate allergic reactions and inflammation. A functional nerve-mast cell interaction has been proposed, given the morphological association between mast cells and neuropeptide-containing peripheral nerves. We now show that purified rat peritoneal mast cells contain large quantities of N -acetylaspartate (NAA; 747.50 nmol/mg of protein). Mast cell levels of NAA were rapidly reduced, by 64.0 and 86.4%, following treatment with compound 48/80 and mastoparan, respectively. These secretagogues strongly decreased mast cell histamine content over the same time period, suggesting also that NAA is stored in secretory granules. The data are the first to show that NAA is present in an immune effector cell type. Because NAA may be involved in myelin synthesis and glutamyl peptide metabolism, NAA released from mast cells following nervous or other stimuli could participate in neuroimmune interactions. Mast cells in multiple sclerosis plaques may contribute to the reported elevations in brain NAA in this disease. 相似文献
150.
Effects of electrically induced fatigue on the twitch and tetanus of paralyzed soleus muscle in humans 总被引:1,自引:0,他引:1
Shields Richard K.; Law Laura Frey; Reiling Brenda; Sass Kelly; Wilwert Jason 《Journal of applied physiology》1997,82(5):1499-1507
Shields, Richard K., Laura Frey Law, Brenda Reiling, KellySass, and Jason Wilwert. Effects of electrically induced fatigueon the twitch and tetanus of paralyzed soleus muscle in humans.J. Appl. Physiol. 82(5):1499-1507, 1997.We analyzed the twitch and summated torque(tetanus) during repetitive activation and recovery of the human soleusmuscle in individuals with spinal cord injury. Thirteen individualswith complete paralysis (9 chronic, 4 acute) had the tibial nerveactivated every 1,500 ms with a 20-Hz train (7 stimuli) for 300 ms anda single pulse at 1,100 ms. The stimulation protocol lasted 3 min andincluded 120 twitches and 120 tetani. Minimal changes were found forthe acute group. The chronic group showed a significant reduction inthe torque and a significant slowing of the contractile speeds of boththe twitch and tetanus. The decrease in the peak twitch torque was significantly greater than the decrease in the peak tetanus torque early during the fatigue protocol for the chronic group. The twitch time to peak and half relaxation time were prolonged during fatigue, which was associated with improved fusion of the tetanus torque. At theend of the fatigue protocol, the decrease in the peak twitch torque wasnot significantly different from the decrease in the peak tetanustorque. After 5 min of rest, the contractile speeds recovered causingthe tetanus to become unfused, but the tetanus torque became lessdepressed than the twitch torque. The differential responses for thetwitch and the tetanus suggest an interplay between optimal fusioncreated from contractile speed slowing and excitation contractioncoupling compromise. These issues make the optimal design of functionalelectrical stimulation systems a formidable task. 相似文献