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At least 1,351 records · Page 75Linked to original sources
PubMed2003

Cyclooxygenase (COX)-2 and COX-1 potentiate beta-amyloid peptide generation through mechanisms that involve gamma-secretase activity.

In previous studies we found that overexpression of the inducible form of cyclooxygenase, COX-2, in the brain exacerbated beta-amyloid (A beta) neuropathology in a transgenic mouse model of Alzheimer's disease. To explore the mechanism through which COX may influence A beta amyloidosis, we used an adenoviral gene transfer system to study the effects of human (h)COX-1 and hCOX-2 isoform expression on A beta peptide generation. We found that expression of hCOXs in human amyloid precursor protein (APP)-overexpressing (Chinese hamster ovary (CHO)-APPswe) cells or human neuroglioma (H4-APP751) cells resulting in 10-25 nM prostaglandin (PG)-E2 concentration in the conditioned medium coincided with an approximately 1.8-fold elevation of A beta-(1-40) and A beta-(1-42) peptide generation and an approximately 1.8-fold induction of the C-terminal fragment (CTF)-gamma cleavage product of the APP, an index of gamma-secretase activity. Treatment of APP-overexpressing cells with the non-selective COX inhibitor ibuprofen (1 microM, 48 h) or with the specific gamma-secretase inhibitor L-685,458 significantly attenuated hCOX-1- and hCOX-2-mediated induction of A beta peptide generation and CTF-gamma cleavage product formation. Based on this evidence, we next tested the hypothesis that COX expression might promote A beta peptide generation via a PG-E2-mediated mechanism. We found that exposure of CHO-APPswe or human embryonic kidney (HEK-APPswe) cells to PG-E2 (11-deoxy-PG-E2) at a concentration (10 nM) within the range of PG-E2 found in hCOX-expressing cells similarly promoted (approximately 1.8-fold) the generation of the CTF-gamma cleavage product of APP and commensurate A beta-(1-40) and A beta-(1-42) peptide elevation. The study suggests that expression of COXs may influence A beta peptide generation through mechanisms that involve PG-E2-mediated potentiation of gamma-secretase activity, further supporting a role for COX-2 and COX-1 in Alzheimer's disease neuropathology.

Alzheimer Disease↗
PubMed2005

Regiochemistry of neuroprostanes generated from the peroxidation of docosahexaenoic acid in vitro and in vivo.

Isoprostanes (IsoPs) are isomers of prostaglandins that are generated from the free radical-initiated peroxidation of arachidonic acid (C20.4 omega-6). IsoPs exert potent bioactivity and are regarded as the "gold standard" to assess oxidative stress in various human diseases. Analogously, autoxidation of docosahexaenoic acid (DHA, C22.6 omega-3) generates an array of IsoP-like compounds that are termed neuroprostanes (NPs). A major class of NPs identified in vitro and in vivo contains F-type prostane rings and are know as F4-NPs. A number of different F4-NP regioisomers are formed from the peroxidation of DHA. Among the eight possible regioisomeric groups, we hypothesize that 4- and 20-series NPs are generated in greater amounts than other classes because the precursors that lead to regioisomers other than those of the 4- and 20-series can be further oxidized to form novel dioxolane-IsoP-like compounds, analogous to those generated from arachidonate. Various mass spectrometric approaches, including electron capture atmospheric pressure chemical ionization mass spectrometry, were utilized to analyze NPs formed in vitro and in vivo based on their characteristic fragmentation in the gas phase. Experimental results were consistent with our hypothesis that 4- and 20-series NP regioisomers are preferentially generated. The discovery of regioselectivity in the formation of NPs will allow studies of the biological activities of NPs to focus on the more abundantly generated compounds to determine their role in modulating the pathophysiological consequences of DHA oxidation and oxidant stress.

Animals↗
PubMed2006

Characterization of the mechanism of cytochrome P450 reductase-cytochrome P450-mediated nitric oxide and nitrosothiol generation from organic nitrates.

Mammalian cytochrome P450 reductase (CPR) and cytochrome P450 (CP) play important roles in organic nitrate bioactivation; however, the mechanism by which they convert organic nitrate to NO remains unknown. Questions remain regarding the initial precursor of NO that serves to link organic nitrate to the activation of soluble guanylyl cyclase (sGC). To characterize the mechanism of CPR-CP-mediated organic nitrate bioactivation, EPR, chemiluminescence NO analyzer, NO electrode, and immunoassay studies were performed. With rat hepatic microsomes or purified CPR, the presence of NADPH triggered organic nitrate reduction to NO2(-). The CPR flavin site inhibitor diphenyleneiodonium inhibited this NO2(-) generation, whereas the CP inhibitor clotrimazole did not. However, clotrimazole greatly inhibited NO2(-)-dependent NO generation. Therefore, CPR catalyzes organic nitrate reduction, producing nitrite, whereas CP can mediate further nitrite reduction to NO. Nitrite-dependent NO generation contributed <10% of the CPR-CP-mediated NO generation from organic nitrates; thus, NO2(-) is not the main precursor of NO. CPR-CP-mediated NO generation was largely thiol-dependent. Studies suggested that organic nitrite (R-O-NO) was produced from organic nitrate reduction by CPR. Further reaction of organic nitrite with free or microsome-associated thiols led to NO or nitrosothiol generation and thus stimulated the activation of sGC. Thus, organic nitrite is the initial product in the process of CRP-CP-mediated organic nitrate activation and is the precursor of NO and nitrosothiols, serving as the link between organic nitrate and sGC activation.

Animals↗
PubMed2004

Fasciola hepatica: cercarial productivity of redial generations in long-surviving Galba truncatula.

Bimiracidial infections of Galba truncatula with Fasciola hepatica were carried out to determine the effect of food quality on the frequency of 1- and 2-sporocyst infections, to analyse its impact on the developmental patterns (normal, or abnormal) of redial generations, and to verify its consequences on cercarial production. These investigations were performed in snails reared at 20 degrees C and provided with cos lettuce and commercial fish food (Tetraphyll) as a food source until their death. Double-sporocyst infections with normal development of redial generations were recorded in 43.9% of infected snails (out of 296). Single-sporocyst infections were noted in the other snails, with normal development of generations in 53.7% and abnormal development (the first mother redia early degenerated) in 2.4%. Four successive redial generations were found in long-surviving snails (more than 90 days). In both 1- and 2-sporocyst infections, showing normal development of generations, the daughter rediae, which exited from the first mother redia (R2a rediae), constituted the greater group of free rediae and produced the highest percentages of cercariae (46.2-48.2%). However, the development of these rediae inside the snail body was slower in 2-sporocyst infections than in 1-sporocyst infections. The numbers of rediae noted in subsequent generations (R2b/R3a and R3b/R4a rediae) were similar, whatever the number of full-grown sporocysts. The number of shed cercariae recorded in the 1- and 2-sporocyst infections did not significantly differ. When long-surviving snails died, 19.8-20.7% of cercariae produced by free rediae (essentially by R2b/R3a and R3b/R4a rediae) were still present in their bodies. The increased frequency of 2-sporocyst infections demonstrated that food quality had a significant effect on the redial burden of F. hepatica developing inside G. truncatula.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Analysis of magnetic resonance imaging acoustic noise generated by a 4.7 T experimental system.

High intensity acoustic noise is an undesirable side-effect in magnetic resonance imaging (MRI) that can cause discomfort and hearing loss in patients and may be an impediment in functional MRI (fMRI) studies of the auditory system. Experimental MRI systems with high magnetic field strengths may generate acoustic noise of higher sound pressure levels (SPLs) than conventional 1.0 and 1.5 T clinical systems. We measured the SPL and spectral content of the acoustic noise generated by the Bruker Biospect 47/40 4.7 T experimental MRI system during scanning sequences commonly used in animal testing. Each sequence generated acoustic noise of high SPL, rapid pulse rates, amplitude-modulated pulse envelopes and multi-peaked spectra. The rapid acquisition with enhancement sequence with a 0.25 mm slice thickness generated SPLs of up to 129 dB peak SPL and 130 dB (A). Fourier analysis of the spectral content of the acoustic noise generated by each MRI sequence showed a wide band of acoustic energy with spectral peaks from 0.2-5 kHz. The intense MRI acoustic impulse noise generated by the 4.7 T system may cause masking of stimuli used in fMRI of the auditory cortex, reduce the hearing acuity of experimental animals and present a risk for unprotected human ears.

Acoustics↗
PubMedDate not supplied

Stimulation and scavestrogen-induced inhibition of reactive oxygen species generated by rat sertoli cells.

The ability of Sertoli cells harvested from 18-day-old Sprague-Dawley rats to generate reactive oxygen species (ROS) occurs under unstimulated and stimulated conditions. Thus, the generation of ROS and its regulation by stimulating and inhibiting compounds was determined as a lucigenin-dependent chemiluminescence reaction. According to the data, ROS generation was influenced by different cell preparation conditions--stimulating substances such as PMA, FMLP, C5a, A23187, and scavestrogens characterized by antioxidant, radical-scavenging properties. The mechanical homogenization during cell preparation procedures leads to an increase of ROS generation. ROS generation of Sertoli cells was followed by elected substances in the following rank order of efficacy: PMA > FMLP > or = C5a > Ca-ionophore A23187. The registered inhibiting effects of the scavestrogens J811 and J861 were significant. The measured CL counts decreased at 72 and 77%, respectively, of control experiments done without scavestrogens. The generation of reactive oxygen species in Sertoli cells and especially the increase in oxygen free radicals and their effects on cellular structures of spermatids are directly involved in inducing morphological alterations. Sertoli cells play an important role in spermatogenesis. The measurements of ROS may have clinical relevance in the evaluation of infertility.

Animals↗
PubMed2005

Generation of hypotheses in Wason's 2-4-6 task: an information theory approach.

We explored the "context of discovery" in Wason's 2-4-6 task, focusing on how the first hypothesis is generated. According to Oaksford and Chater (1994a) people generate hypotheses extracting "common features", or regularities, from the available triples, but their model does not explain why some regularities contribute to the hypothesis more than do other regularities. Our conjecture is that some regularities contribute to the hypothesis more than do other regularities because people estimate the amount of information in the perceived regularities and try to preserve as much information as possible in their initial hypotheses. Experiment 1, which used two initial triples, showed that the presence of high-information relational regularities in the initial triples affected the information in the initial hypotheses more than did the presence of low-information object regularities. Experiment 2 extended the results to the classic situation in which only one initial triple is given. It also suggested that amount of information is the only aspect of the structure of the triple that affects hypotheses generation. Experiment 3 confirmed the latter finding: Although relations are commonly distinguished between first-order and higher order relations, the latter being most important for generating hypotheses (Gentner, 1983), higher order relations do have an effect on Wason's 2-4-6 task only if their presence incre ases information. In the conclusion we discuss the statistical soundness of human hypotheses generation processes, and we ask an unanswered question: Amount of information explains why some regularities are preferred to others, but only within a set of "nonarbitrary" regularities; there are object regularities that are rich in information content, but are considered "arbitrary", and are not used in generating hypotheses. Which formal property can distinguish between these two sets of regularities?

Adult↗
PubMedDate not supplied

Differential actions of naftopidil, doxazosin and nifedipine on platelet thromboxane generation and platelet-derived growth factor efflux in vitro.

We examined the effects of the alpha(1)-adrenoreceptor blockers naftopidil and doxazosin and the Ca(2+) antagonist nifedipine on platelet function with reference to stimulus-induced thromboxane (TxB(2)) generation and platelet-derived growth factor (PDGF) efflux. Collagen (5 micro g/ml) caused a 12.5-fold increase in TxB(2) generation, from a basal level of 7.69 +/- 1.28 ng/10(8) platelets to 96.34 +/- 13.37 ng/10(8) platelets (P<0.001). Adrenaline (16 micro M) increased TxB(2) production 3-fold from 2.44 +/- 0.61 to 8.02 +/- 1.08 ng/10(8) platelets (P<0.01). Adrenaline-induced TxB(2) generation was inhibited 42.5 +/- 10.3% (P<0.05) and 81.8 +/- 7.5% (P<0.05) by 10 and 40micro M naftopidil, respectively. Collagen-stimulated TxB(2) generation was inhibited 59.5 +/- 9.2% (P<0.01) by 40 micro M naftopidil and 53.7 +/- 11.3% (P<0.01) by 28 micro M nifedipine. Doxazosin (7.5 and 30 micro M) did not influence adrenaline- or collagen-induced TxB(2) synthesis. Collagen increased PDGF efflux from 1.17 +/- 0.39 to 4.25 +/- 0.51 ng/10(8) platelets (P<0.01), whilst adrenaline raised concentrations from 1.08 +/- 0.19 to 5.37 + 1.02 ng/10(8) platelets (P<0.01). Naftopidil had no effect on collagen-induced PDGF release. Adrenaline-stimulated PDGF efflux was, however, inhibited 82.9 +/- 13.7% (P<0.001) and 125.7 +/- 16.3% (P<0.001) by 10 and 40 micro M naftopidil, respectively. Doxazosin (30 micro M) inhibited adrenaline-induced PDGF release by 70.3 +/- 31.5% (P<0.05), whilst nifedipine (28 micro M) had no effect on collagen-stimulated release. We conclude that naftopidil, like nifedipine, may block stimulated TxB(2) generation via inhibition of phospholipase A(2), the Ca(2+)-dependent, rate-limiting enzyme in thromboxane synthesis. Although adrenaline-induced PDGF release was inhibited by naftopidil and doxazosin, collagen-induced release was unaffected by either alpha(1)-adrenoreceptor blocker or nifedipine, indicating that platelet alpha-granular release is not dependent on Ca(2+) mobilisation or thromboxane generation. Thus, the effects of these drugs on PDGF release may be mediated through alternative cellular signalling mechanisms.

Adrenergic alpha-Antagonists↗
PubMed2003

Irradiation of cells with ultraviolet-A (320-400 nm) in the presence of cell culture medium elicits biological effects due to extracellular generation of hydrogen peroxide.

Biological effects of ultraviolet A (UVA) irradiation have been ascribed to the photochemical generation of singlet oxygen. Not all effects described in the literature, however, are explicable solely by the generation of singlet oxygen, but rather resemble effects elicited by hydrogen peroxide (H2O2). Here, we show that when cells are kept in cell culture media during exposure to UVA, stress kinases, including ERK 1 and ERK 2 as well as Akt (protein kinase B), are activated, whereas there is no or only minor activation when cells are kept in phosphate-buffered saline during irradiation. Indeed, the exposure of cell culture media to UVA (30 J/cm2) results in the generation of significant amounts of H2O2, with concentrations of about 100 microM. H2O2 concentrations are at least three-fold higher in HEPES-buffered culture media after UVA irradiation. From experiments with solutions of riboflavin, tryptophan or HEPES, as well as combinations thereof, it is concluded that riboflavin mediates the photooxidation of either tryptophan or HEPES, resulting in the generation of H2O2. Thus, if signaling effects of UVA radiation are to be investigated in cell culture systems, riboflavin and HEPES/tryptophan should be avoided during irradiation because of artificial H2O2 generation. It should be taken into account, however, that in vivo tryptophan and riboflavin might play an important role in the generation of reactive oxygen species by UVA as both substances are abundant in living tissues.

Animals↗
PubMed2003

Factors affecting the ascorbate- and phenolic-dependent generation of hydrogen peroxide in Dulbecco's Modified Eagles Medium.

Ascorbate and several polyphenolic compounds have been reported to undergo oxidation in cell culture media to generate hydrogen peroxide (H2O2), but the mechanism underlying this has not been established. We therefore investigated the parameters affecting H2O2 production. H2O2 generation from ascorbate, gallic acid and other phenolic compounds in Dulbecco's Modified Eagles' Medium (DMEM) at 37 degrees C under 95% air - 5% CO2 was not significantly inhibited by high (5-10 mM) concentration of EGTA, o-phenanthroline or desferriox-amine, but partial inhibition by EDTA and diethylene-triaminepentaacetic acid (DTPA) was observed. Incubation of DMEM alone at 37 degrees C led to an upward drift of pH, even under an atmosphere of 95% air - 5% CO2. Prevention of this pH rise by increasing the concentration of N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] (Hepes) buffer lowered the levels of H2O2 generated by ascorbate and phenolic compounds, but there was still substantial H2O2 generated at pH 7.4. Mixtures of ascorbate and phenolic compounds led to less H2O2 generation than would be expected from the rates observed with ascorbate or phenolic compounds alone. Ascorbate prevented the loss of gallic acid incubated in DMEM. The role of metal ions and other constituents of the culture medium in promoting H2O2 generation is discussed.

Ascorbic Acid↗
PubMed2006

Hospitalization due to alcohol and drug abuse in first- and second-generation immigrants: a follow-up study in Sweden.

The detrimental effects of substance abuse on the individual and on society are well known. Health care resources must target where they are most needed. This study investigated (1) whether the increased risk of being hospitalized for alcohol abuse and drug abuse among certain immigrant groups is present in the next generation and (2) whether having one parent born in the host country (i.e., Sweden) has a protective effect on the risk of being hospitalized for alcohol abuse and drug abuse among second-generation immigrants. In total, 2,243,546 persons aged 20-39 years were followed from 1 January 1992 until 31 December 1999 for first hospital admission due to alcohol abuse or drug abuse. A Cox regression model was used to estimate hazard ratios for each diagnosis group. When the Swedish majority population was used as reference, the highest risks of alcohol abuse and drug abuse were found among first- and second-generation Finns, after adjustment for income. Among second-generation Finns with one parent born in Sweden, the increased risk of being hospitalized for alcohol abuse and drug abuse was lower than among second-generation Finns with both parents born in Finland. Health care resources need to target certain groups of first- and second-generation immigrants.

Adult↗
PubMed1998

Enhancement of hydroxyl radical generation in the Fenton reaction by alpha-hydroxy acid.

The effect of various organic acids on hydroxyl radical (.OH) generation in the Fenton reaction were examined by the ESR spin trapping technique, where 5,5-dimethyl-1-pyroline-N-nitroxide (DMPO) and alpha-phenyl-tert-butyl nitrone (PBN) were used as the spin trapping reagents. alpha-Hydroxy acids such as lactic acid, glycolic acid and 2-hydroxy isobutyric acid were found to markedly enhance .OH generation in the reaction. In contrast, beta-hydroxy acid, alpha-keto acid, esters of alpha-hydroxy acids, aldehydes and other straight chain organic acids had no such enhancing activity. alpha-Amino acids had also no enhancing effect. The results suggest that the alpha-hydroxy acid moiety is prerequisite for the enhancement of .OH generation in the Fenton reaction. Superoxide dismutase did not inhibit the enhancing effect of alpha-hydroxy acids whereas catalase completely inhibited the .OH generation. Thus, alpha-hydroxy acids directly enhanced the .OH generation via the Fenton reaction but not the Haber-Weiss reaction. Possible role of lactic acid manipulating .OH generation is discussed in relation to the ischemia-reperfusion cell damage.

Catalase↗
PubMed1980

Aerosol generation to simulate specific industrial fine particle effluents.

Techniques were developed for generating large quantities of fine particle metal oxide aerosols. The aerosols were generated by burning flammable solutions containing appropriate soluble compounds (nitrates, for example) of the desired elements. In the flame these compounds generally decomposed to oxides. The generated aerosol flow rates were as high as 42 m3 per minute (1500 cfm); the mass concentrations were as high as 16.8 g per m3 at STP. For most aerosols the particle concentrations were of the order of 10(9) particles per cm3. Electron microscopic pictures (SEM and TEM) of precipitated particles show that many of the larger particles (20 microm) are hollow and that the smaller particles (0.01 microm) are aggregated. Specific aerosols were generated to simulate the fine particulate effluents generated by combustion of pulverized coal (electricity generation) electric arc and basic oxygen furnaces (iron and steel production) and zinc smelters. Methods were developed to vary the sulfur dioxide concentration and the electrical resistivities of the simulants for coal combustion.

Aerosols↗
PubMed1996

Generation effects and the lack thereof: the role of transfer-appropriate processing.

We report two experiments designed to test a multifactor transfer-appropriate processing explanation of generation effects, and the lack thereof, in free recall and cued recall. The basic argument is that the act of generating a target enhances the processing of one or more possible types of information (e.g. target-specific information, cue-target relationships, or target-target relationships) and that subsequent retention tests will reveal an advantage (or disadvantage) of such generation (compared to a "read" control) to the degree that a test is sensitive to the information on which processing was focused during study. Across the two experiments, manipulations of identical stimulus materials forced subjects to process different types of information in order to generate targets, producing a striking reversal in the relative levels of free recall and cued recall for targets that had been generated vs. read, and lending strong support to the transfer-appropriate processing aspect of the proposed framework for explaining generation effects.

Association Learning↗
PubMed2005

Variations in hospital waste quantities and generation rates.

The relationship between public health and improper collection, handling, and disposal of solid wastes in general, and hospital wastes in particular, is quite clear. Hazardous and nonhazardous wastes generated from different divisions of two of the largest public hospitals (capacity of approximately 400 beds each) in Kuwait were quantified and generation rates were determined. The generation rates were related to some important factors such as the number of patients, number of beds, and the type of activity conducted in different sections of the hospitals. The relationship between the waste generation rate and the number of patients was more applicable than that expressed in terms of the number of beds. The rates observed were in the range of 4.89 to 5.4 kg/patient/day, which corresponds to 3.65 to 3.97 kg/bed/day, respectively. These generation rates were comparable with those reported in the literature for similar hospitals. Minimal waste quantities were collected in the weekends. The study indicated that the hospitals surveyed provide some segregation of hazardous and nonhazardous wastes. Hazardous wastes contributed about 53% of the total quantity of wastes generated at the hospitals.

Data Collection↗
PubMed1967

Generation of chemotactic activity in rabbit serum by plasminogen-streptokinase mixtures.

The addition of plasminogen and streptokinase to rabbit serum results in appearance of chemotactic activity which is relatively heat-labile and dialyzable. Generation of this activity requires heat-labile factors in serum, but not the sixth component of complement. The optimal mole ratio for generation of chemotactic activity is 1:1 to 1:3 for plasminogen to streptokinase. Neither material alone is sufficient to generate the activity in fresh serum. Generation of chemotactic activity can be blocked by the presence of epsilon-aminocaproic acid. This plasmin-generated chemotactic factor sediments slowly in a sucrose density gradient during ultracentrifugation. The addition of plasminogen and streptokinase to rabbit serum containing the preformed chemotactic factor (activated trimolecular complex of C'5, C'6, C'7) causes destruction of the chemotactic factor and loss of hemolytic activity of the sixth component of complement. The same mole ratio of reactants for optimal expression of the phenomenon holds as for plasmin generation of chemotactic activity in untreated serum.

Animals↗
PubMed1968

Interactions of the complement system with endotoxic lipopolysaccharide. Generation of a factor chemotactic for polymorphonuclear leukocytes.

Endotoxic lipopolysaccharide has recently been shown to fix large amounts of the complement components related to the biologic activities mediated by that system. The present study sought to determine whether the generation of chemotactic factor by endotoxin in serum was dependent upon complement system activation. Preheating serum, incubating at 0 degrees C, or incubating in the presence of EDTA, all prevented chemotactic factor generation as well as complement fixation by endotoxin. "Endotoxoids" deficient in complement-firing activity were also deficient in chemotactic factor generation. Chemotactic factor could not be generated by endotoxin in sera of mice congenitally deficient in the C'S component of complement, while chemotactic factor was generated by endotoxin in the sera of coisogenic mice with normal complement levels for that species. The chemotactic factor induced by endotoxin was heat stable and nondialyzable. Molecular sieve chromatography and sucrose density gradient ultracentrifugation demonstrated that the chemotactic factor was a relatively low molecular weight product (15,000-30,000) and as such different from previously scribed C' system-derived chemotactic factors. These experiments demonstrate that generation of chemotactic factor by endotoxin in serum is dependent upon C' system activation involving at least C'5. Furthermore, the relatively low molecular weight of this factor suggests that it might be derived from activation of a single complement component rather than from complexing of multiple complement components.

Animals↗
PubMed1995

Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes.

It has previously been shown that bone marrow-generated dendritic cells (DC) are potent stimulators in allogeneic mixed leukocyte reactions and are capable of activating naive CD4+ T cells in situ in an antigen-specific manner. In this study we have investigated whether bone marrow-generated DC are capable of inducing antigen-specific CD8+ T cell responses in vivo. Initial attempts to induce specific cytotoxic T lymphocyte (CTL) responses in mice injected with bone marrow-generated DC pulsed with ovalbumin (OVA) peptide were frustrated by the presence of high levels of nonspecific lytic activity, which obscured, though not completely, the presence of Ag-specific CTL. Using conditions that effectively differentiate between antigen-specific and nonspecific lytic activity, we have shown that bone marrow-generated DC pulsed with OVA peptide are potent inducers of OVA-specific CTL responses in vivo, compared with splenocytes or RMA-S cells pulsed with OVA peptide, or compared with immunization with free OVA peptide mixed with adjuvant. Antibody-mediated depletion experiments have shown that the cytotoxic effector cells consist primarily of CD8+ cells, and that induction of CTL in vivo is dependent on CD4+ as well as on CD8+ T cells. These results provide the basis for exploring the role of bone marrow-generated DC in major histocompatibility class I-restricted immune responses, and they provide the rationale for using bone marrow-generated DC in CTL-mediated immunotherapy of cancer and infectious diseases.

Adjuvants, Immunologic↗