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Biomedical subjects

X Fan

Publications and source records attributed to X Fan.

At least 37 records · Page 2Linked to original sources
PubMed2000

Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide.

The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppressive effects of cannabinoids. Unfortunately, there was a dearth of pharmacological studies with the endocannabinoids and human CB2 (hCB2). These studies compare and contrast the potency and efficacy of anandamide, 2-AG, and the synthetic cannabinoid HU210 at hCB2. Using [(35)S]guanosine-5'-O-(3-thio)triphosphate (GTPgammaS) and radioligand bindings in insect Sf9-hCB2 membranes, we showed that both endocannabinoids bound hCB2 with similar affinity and that the cannabinoids acted as full agonists in stimulating [(35)S]GTPgammaS exchange, although 2-AG was 3-fold more potent than anandamide (EC(50) = 38.9 +/- 3.1 and 121 +/- 29 nM, respectively). In a mammalian expression system (Chinese hamster ovary-hCB2 cells), HU210 and 2-AG maximally inhibited forskolin-stimulated cAMP synthesis (IC(50) = 1.61 +/- 0.42 nM and 1.30 +/- 0.37 microM, respectively) although anandamide was ineffective. In Chinese hamster ovary-hCB2 membranes, HU210 and 2-AG were also full agonists in stimulating [(35)S]GTPgammaS binding (EC(50) = 1.96 +/- 0.35 and 122 +/- 17 nM, respectively), but anandamide was a weak partial agonist (EC(50) = 261 +/- 91 nM; 34 +/- 4% of maximum). Due to its low intrinsic activity, coincubation with anandamide effectively attenuated the functional activity of 2-AG at hCB2. Collectively, the data showed that both endocannabinoids bound hCB2 with similar affinity, but only 2-AG functioned as a full agonist. Moreover, the agonistic activity of 2-AG was attenuated by anandamide.

Animals↗
PubMed1999

The Discovery of a High-Redshift Quasar without Emission Lines from Sloan Digital Sky Survey Commissioning Data.

We report observations of a luminous unresolved object at redshift z=4.62, with a featureless optical spectrum redward of the Lyalpha forest region, discovered from Sloan Digital Sky Survey commissioning data. The redshift is determined by the onset of the Lyalpha forest at lambda approximately 6800 Å and a Lyman limit system at lambda=5120 Å. A strong Lyalpha absorption system with weak metal absorption lines at z=4.58 is also identified in the spectrum. The object has a continuum absolute magnitude of -26.6 at 1450 Å in the rest frame (h0=0.5, q0=0.5) and therefore cannot be an ordinary galaxy. It shows no radio emission (the 3 sigma upper limit of its flux at 6 cm is 60 µJy), indicating a radio-to-optical flux ratio at least as small as that of the radio-weakest BL Lacertae objects known. It is also not linearly polarized to a 3 sigma upper limit of 4% in the observed I band. Therefore, it is either the most distant BL Lac object known to date, with very weak radio emission, or a new type of unbeamed quasar, whose broad emission line region is very weak or absent.

Journal Article↗
PubMed1999

Protein kinase C phosphorylated at a conserved threonine is retained in the cytoplasm.

Phosphorylation of calcium-activated protein kinase Cs (PKCs) at threonine 634 and/or threonine 641 increases during long term potentiation or associative learning in rodents. In the marine mollusk Aplysia, persistent activation of the calcium-activated PKC Apl I occurs during long term facilitation. We have raised an antibody to a peptide from PKC Apl I phosphorylated at threonines 613 and 620 (sites homologous to threonines 634 and 641). This antibody recognizes PKC Apl I only when it is phosphorylated at threonine 613. Both phorbol esters and serotonin increase the percentage of kinase phosphorylated at threonine 613 in Aplysia neurons. Furthermore, the pool of PKC that is phosphorylated at threonine 613 in neurons is resistant to both membrane translocation and down-regulation. Replacement of threonine 613 with alanine increased the affinity of PKC Apl I for calcium, suggesting that phosphorylation of this site may reduce the ability of PKC Apl I to translocate to membranes in the presence of calcium. We propose that phosphorylation of this site is important for removal of PKC from the membrane and may be a mechanism for negative feedback of PKC activation.

Amino Acid Sequence↗
PubMed1999

Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents.

Long chain fatty acid transport is selectively up-regulated in adipocytes of Zucker fatty rats, diverting fatty acids from sites of oxidation toward storage in adipose tissue. To determine whether this is a general feature of obesity, we studied [(3)H]oleate uptake by adipocytes and hepatocytes from 1) homozygous male obese (ob), diabetic (db), fat (fat), and tubby (tub) mice and from 2) male Harlan Sprague-Dawley rats fed for 7 weeks a diet containing 55% of calories from fat. V(max) and K(m) were compared with controls of the appropriate background strain (C57BL/6J or C57BLKS) or diet (13% of calories from fat). V(max) for adipocyte fatty acid uptake was increased 5-6-fold in ob, db, fat, and tub mice versus controls (p < 0.001), whereas no differences were seen in the corresponding hepatocytes. Similar changes occurred in fat-fed rats. Of three membrane fatty acid transporters expressed in adipocytes, plasma membrane fatty acid-binding protein mRNA was increased 9-11-fold in ob and db, which lack a competent leptin/leptin receptor system, but was not increased in fat and tub, i.e. in strains with normal leptin signaling capability; fatty acid translocase mRNA was increased 2.2-6.5-fold in tub, ob, and fat adipocytes, but not in db adipocytes; and only marginal changes in fatty acid transport protein 1 mRNA were found in any of the mutant strains. Adipocyte fatty acid uptake is generally increased in murine obesity models, but up-regulation of individual transporters depends on the specific pathophysiology. Leptin may normally down-regulate expression of plasma membrane fatty acid binding protein.

Adipocytes↗
PubMed1999

MK-801-induced expression of Fos protein family members in the rat retrosplenial granular cortex.

The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 has been shown to induce an acute Fos and Fos-related antigen (Fra) expression in the rat retrosplenial granular cortex (RSG), but the exact composition of the Fos protein family and their individual dynamic alterations are unknown. We examined this issue using immunocytochemistry and Western blot analysis with two antibodies that recognize, respectively, Fos and all the identified members of Fos protein family. Immunocytochemistry detected a rapid and transient expression of Fos proteins in some RSG neurons and a delayed and prolonged expression of Fra proteins in most RSG neurons following a single systemic MK-801 injection (1 mg/kg). Multiple MK-801 injections (i.e., ten consecutive injections once every other day; 1 mg/kg) produced a moderate Fra expression but failed to induce detectable Fos expression. Western blot analysis further showed a transient expression of 72-kDa Fos proteins following a single MK-801 injection and a prolonged expression of 46- and 43-kDa Fra proteins after either a single or multiple MK-801 administration. The delayed onset and prolonged expression of these Fra proteins suggest that they may be DeltaFosB. The possible relevance of these results to clinical psychotomimetic effects of the NMDA receptor antagonists phencyclidine and ketamine is discussed.

Animals↗
PubMed1999

Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for multiple inputs.

Lysophosphatidic acid (LPA) is a growth factor that exerts a number of well characterized biological actions on fibroblasts and other cells. In the present study, we investigated the possibility that LPA activates the transcription factor NF-kappaB. NF-kappaB is a target of cytokines, but its activation by other classes of agonists has raised considerable interest in the control of processes such as inflammation and wound healing through varied mechanisms. We find that LPA causes a marked activation of NF-kappaB in Swiss 3T3 fibroblasts as determined by the degradation of IkappaB-alpha in the cytosol and the emergence of kappaB binding activity in nuclear extracts. The EC50 for activation of NF-kappaB is 1-5 microM, a range similar to that reported for reinitiation of DNA synthesis and activation of the serum response element. Activation of NF-kappaB is attenuated by pertussis toxin and inhibitors of protein kinase C, and it is completely blocked by the Ca2+ chelator BAPTA-AM. The combination of phorbol ester and thapsigargin promotes an activation comparable with that of LPA. Activation by LPA is additionally inhibited by tyrphostin A25 but not genistein or AG1478, indicating a selective utilization of protein-tyrosine kinases, and by certain antioxidants, implying a role for reactive oxygen species. The activation is also inhibited by tricyclodecan-9-yl-xanthogenate (D609), implying a requirement for hydrolysis of phosphatidylcholine. The data demonstrate the utilization of multiple pathways in the activation of NF-kappaB by LPA, not inconsistent with the relevance of several families of GTP-binding regulatory proteins.

3T3 Cells↗
PubMed1999

Role of NFkappaB in the regulation of macrophage colony stimulating factor by tumor necrosis factor-alpha in ST2 bone stromal cells.

Expression of MCSF in bone is important to the regulation of osteoclastogenesis. We show here that tumor necrosis factor-alpha (TNFalpha) increases the production of both soluble (sMCSF) and membrane-bound (mMCSF) macrophage colony stimulating factor by ST2 bone stromal cells. Treatment of ST2 cells with TNFalpha caused sMCSF levels to increase by 394+/-5% from basal; mMCSF rose by 316+/-66% from 30+/-10 per 100,000 cells in the same time. These increases were consistent with increased expression of mRNAs encoding both isoforms. Increases in MCSF mRNA are also seen after stimulation with dexamethasone. To investigate the potential role of NFkappaB in this TNFalpha effect, we treated cells with sodium salicylate (NaS), an inhibitor of NFkappaB translocation. NaS decreased TNFalpha-stimulated NFkappaB activation by 50% as assessed by EMSA. Despite inhibition of NFkappaB signaling, NaS enhanced TNFalpha-stimulated MCSF secretion and did not prevent TNFalpha-stimulated increases in sMCSF mRNA, suggesting that NFkappaB was not involved in TNFalpha effect on the gene. TNFalpha failed to stimulate transcription of a 774 nucleotide MCSF promoter-luciferase reporter transfected into ST2 cells which contained the NFkappaB consensus sequence. Deletion of the seven nucleotides containing the NFkappaB homology response sequence from the MCSF promoter increased basal gene transcription by twofold. TNFalpha thus contributes to an osteoclastogenic environment through upregulation of bone expression of both MCSF isoforms. Our data suggests that NFkappaB is not the major signaling pathway through which this occurs.

Bone and Bones↗
PubMed1999

Simplified model and measurement of specific absorption rate distribution in a culture flask within a transverse electromagnetic mode exposure system.

In vitro experiments in bioelectromagnetics frequently require the determination of specific absorption rate (SAR) within a layer of cells on the bottom of a culture flask when the SAR has rapid spatial variation both horizontally within the cell layer and vertically in the medium bathing the cells. This problem has only recently been treated in the literature; and it is here approached differently for another irradiation system. It is shown that a simple two-dimensional frequency-domain guided-wave treatment yields results qualitatively comparable to those of more computationally intensive three-dimensional time-domain free-field scattering treatments. The problem of inferring local SARs from temperature-vs.-time curves is shown to be seriously confounded by thermal diffusion; and specific analytic and numerical results are presented to aid in understanding this effect. A novel experimental technique is introduced for measuring millikelvin temperature offsets with subsecond resolution, and illustrative experimental data are presented. Finally, present experimental and theoretical uncertainties are considered; and it is pessimistically asserted that, in a culture flask where spatial SAR variation is rapid, point SAR measurements by thermal methods may be in error by as much as +/- 3 dB. More reliable thermal determinations will require extreme care, challenging technological innovations, or both.

Cells, Cultured↗
PubMed1999

Osteoclastogenesis is repressed by mechanical strain in an in vitro model.

Functional loading provides a site-specific signal for the regulation of bone mass and morphology. To determine if strain can inhibit the resorptive component of bone remodeling, osteoclast formation was assessed in marrow cultures plated on flexible membranes subjected to 5% strain for 10 cycles/minute, 24 hours per day. Cultures strained during days 2 through 7 inhibited osteoclast formation to 61+/-7% of control cultures (p < 0.05), a degree of inhibition similar to that observed when the cultures were subjected to strains during only days 2 through 4 but also evaluated on day 7 (67+/-4% of control; p < 0.05). In contrast, straining of cultures during days 5 through 7 had little influence on inhibiting the formation of osteoclasts (94+/-5% of control; no significant difference). The nonuniformly strained substrate was subdivided into three concentric rings. and cultures were used to examine the site-specificity of the inhibition caused by strain. Osteoclast formation in the outermost boundary, which was distended from 3.6 to 5%, was 41+/-7% of that observed in outer regions of control wells. The inhibitory potential of mechanical strain was reduced within the middle ring (73+/-6% of control osteoclasts: p < 0.01), where the strain ranged from 0.2 to 3.6%. The central region, which experienced strains equivalent to those in the middle ring (0.2 to -4% strain), showed inhibition of osteoclast formation to a similar degree (75+/-6% of control). Media harvested from strained cultures failed to inhibit osteoclast formation in unstrained cultures; this implies that the inhibitory effect of strain depended on the direct interaction of the cell with the substrate rather than by a humoral factor. A second device, where a uniform strain was delivered at 1.8% throughout the entire plate, inhibited osteoclast recruitment to 48+/-3.6%, emphasizing that uniform strain in the absence of shear stress constrains osteoclast recruitment. These in vitro experiments can but model the complex environment generated by in vivo mechanical strains: however, they provide the first direct evidence that strain must be considered as inhibitory to osteoclast recruitment.

Animals↗
PubMed1999

Ultrasound power deposition model for the chest wall.

An ultrasound power deposition model for the chest wall was developed based on secondary-source and plane-wave theories. The anatomic model consisted of a muscle-ribs-lung volume, accounted for wave reflection and refraction at muscle-rib and muscle-lung interfaces, and computed power deposition due to the propagation of both reflected and transmitted waves. Lung tissue was assumed to be air-equivalent. The parts of the theory and numerical program dealing with reflection were experimentally evaluated by comparing simulations with acoustic field measurements using several pertinent reflecting materials. Satisfactory agreement was found. A series of simulations were performed to study the influence of angle of incidence of the beam, frequency, and thickness of muscle tissue overlying the ribs on power deposition distributions that may be expected during superficial ultrasound (US) hyperthermia of chest wall recurrences. Both reflection at major interfaces and attenuation in bone were the determining factors affecting power deposition, the dominance of one vs. the other depending on the angle of incidence of the beam. Sufficient energy is reflected by these interfaces to suggest that improvements in thermal doses to overlying tissues are possible with adequate manipulation of the sound field (advances in ultrasonic heating devices) and prospective treatment planning.

Computer Simulation↗
PubMed1999

The value of assessing pulmonary venous flow velocity for predicting severity of mitral regurgitation: A quantitative assessment integrating left ventricular function.

Although alteration in pulmonary venous flow has been reported to relate to mitral regurgitant severity, it is also known to vary with left ventricular (LV) systolic and diastolic dysfunction. There are few data relating pulmonary venous flow to quantitative indexes of mitral regurgitation (MR). The object of this study was to assess quantitatively the accuracy of pulmonary venous flow for predicting MR severity by using transesophageal echocardiographic measurement in patients with variable LV dysfunction. This study consisted of 73 patients undergoing heart surgery with mild to severe MR. Regurgitant orifice area (ROA), regurgitant stroke volume (RSV), and regurgitant fraction (RF) were obtained by quantitative transesophageal echocardiography and proximal isovelocity surface area. Both left and right upper pulmonary venous flow velocities were recorded and their patterns classified by the ratio of systolic to diastolic velocity: normal (>/=1), blunted (<1), and systolic reversal (<0). Twenty-three percent of patients had discordant patterns between the left and right veins. When the most abnormal patterns either in the left or right vein were used for analysis, the ratio of peak systolic to diastolic flow velocity was negatively correlated with ROA (r = -0.74, P <.001), RSV (r = -0.70, P <.001), and RF (r = -0.66, P <.001) calculated by the Doppler thermodilution method; values were r = -0.70, r = -0.67, and r = -0.57, respectively (all P <.001), for indexes calculated by the proximal isovelocity surface area method. The sensitivity, specificity, and predictive values of the reversed pulmonary venous flow pattern for detecting a large ROA (>0.3 cm(2)) were 69%, 98%, and 97%, respectively. The sensitivity, specificity, and predictive values of the normal pulmonary venous flow pattern for detecting a small ROA (<0.3 cm(2)) were 60%, 96%, and 94%, respectively. However, the blunted pattern had low sensitivity (22%), specificity (61%), and predictive values (30%) for detecting ROA of greater than 0.3 cm(2) with significant overlap with the reversed and normal patterns. Among patients with the blunted pattern, the correlation between the systolic to diastolic velocity ratio was worse in those with LV dysfunction (ejection fraction <50%, r = 0.23, P >.05) than in those with normal LV function (r = -0.57, P <.05). Stepwise linear regression analysis showed that the peak systolic to diastolic velocity ratio was independently correlated with RF (P <.001) and effective stroke volume (P <.01), with a multiple correlation coefficient of 0.71 (P <.001). In conclusion, reversed pulmonary venous flow in systole is a highly specific and reliable marker of moderately severe or severe MR with an ROA greater than 0.3 cm(2), whereas the normal pattern accurately predicts mild to moderate MR. Blunted pulmonary venous flow can be seen in all grades of MR with low predictive value for severity of MR, especially in the presence of LV dysfunction. The blunted pulmonary venous flow pattern must therefore be interpreted cautiously in clinical practice as a marker for severity of MR.

Aged↗
PubMed1999

Development of apple superficial scald, soft scald, core flush, and greasiness is reduced by MCP.

1-Methylcyclopropene (MCP) was used to evaluate the role of ethylene in development of apple (Malus x domestica Borkh.) physiological disorders during storage. Granny Smith, Red Chief Delicious, and Fuji apple fruit were treated with MCP at a concentration of 1 microL L(-)(1) for 12 h at 20 degrees C. For all varieties stored at 0 degrees C, ethylene production and respiration rates were reduced for several months following MCP treatment, and firmness and titratable acidity of treated fruit were higher compared to controls. Apples treated with MCP did not develop superficial scald or peel greasiness through 6 months storage plus ripening at 20 degrees C for 7 days. Core flush was not observed in MCP-treated fruit until 6 months after treatment when the incidence was still lower compared to control fruit. MCP delayed the rise in production of alpha-farnesene and reduced accumulation of its oxidation products.

Cyclopropanes↗
PubMed1999

Impact of 1-methylcyclopropene and methyl jasmonate on apple volatile production.

Climacteric Fuji apples were treated with 10 microL x L(-1) MCP (1-methylcyclopropene), 2 mmol x L(-1) MJ (methyl jasmonate), or a combination of 10 microL x L(-1) MCP and 2 mmol x L(-1) MJ. Fruit were kept at 20 degrees C for 15 days after treatment. Production of ethylene and other volatile compounds was measured prior to and 3, 7, 11, and 15 days after treatment. Ethylene production decreased 3 days following MJ treatment and then increased. MCP treatment alone or in combination with MJ inhibited ethylene production. MJ and MCP inhibited production of many volatile alcohols and esters. The production of individual alcohols and esters appears to be differentially inhibited by MJ or MCP. MJ and MCP inhibited not only production of alcohols but also formation of esters from alcohols.

Acetates↗
PubMed1999

Cloning and expression of Aplysia carboxypeptidase D, a candidate prohormone-processing enzyme.

Many peptide hormones in a variety of species are produced from larger precursors by limited proteolysis at basic amino acid-containing sites. The marine mollusc Aplysia has homologs of mammalian peptide-processing enzymes, including furin, prohormone convertase 1 (PC1), PC2, and carboxypeptidase E (CPE). A novel neuronal Aplysia enzyme was recently identified that was most closely related to carboxypeptidase D (CPD; Fan and Nagle, DNA Cell Biol. 15, 937-945, 1996), a second carboxypeptidase thought to be present in the secretory pathway and to contribute to peptide hormone processing. We have identified and cloned multiple overlapping bag-cell neuron cDNAs that encode two proteins that are members of the CPD family. Sequence analyses demonstrate that the longer CPD protein (1446 residues) contains an N-terminal signal peptide and four carboxypeptidase-like domains; the third and fourth domains are not predicted to form active enzymes, as several critical residues are absent. The shorter CPD protein is predicted to contain two active carboxypeptidase-like domains. Northern blot analysis identified a major Aplysia CPD mRNA (5.3 kb) and several smaller minor transcripts in central nervous system tissue. The CPD was purified from Aplysia ovotestis using a method previously developed for mammalian CPD. The purified Aplysia CPD binds antisera raised against regions of the protein encoded by the Aplysia cDNA clone, as well as an antiserum raised against duck CPD. The enzymatic properties of purified Aplysia CPD are generally similar to those of mammalian CPD. Aplysia CPD is a candidate prohormone-processing enzyme that may play a role in the processing of Aplysia prohormones in the secretory pathway.

Amino Acid Sequence↗
PubMed1999

Comparison of genetic heterogeneity of hepatitis C viral RNA in liver tissue and serum.

OBJECTIVE: Hepatitis C virus (HCV) is known to be heterogeneous and to circulate as a group of closely related quasispecies in individual patients, although hepatic viral genetic characteristics have not been well documented. METHODS: Matched serum and liver samples were tested by reverse transcription polymerase chain reaction amplification and single stranded conformation polymorphism analysis of the hypervariable portion of the E2/NS1 region of the HCV genome. The number of quasispecies was compared with the amount of HCV RNA, HCV genotyping, and infection with the hepatitis G virus. RESULTS: Sixteen of 40 patients had HCV RNA detectable in serum and liver. The HCV genotype was identical in serum and liver of all but one case. HCV RNA levels were approximately 10-fold higher in liver than serum. The number of HCV quasispecies in serum ranged between two and six (median 3.0) and in the liver between 2 and 19 (median 3.5, mean liver/serum ratio 1 to 6.3, median 1.8). The number of quasispecies in liver was equal to or greater than that in serum in all cases. HGV infection was found in 14 cases and did not influence serum or hepatic levels of HCV RNA. CONCLUSIONS: The number of hepatic HCV quasispecies usually exceeds that in serum, independent of the amount of HCV RNA and HCV genotype. This finding is compatible with clearance of some quasispecies from serum, but not liver, by putative neutralizing antibodies.

Adult↗
PubMed1999

Experimental assessment of power and temperature penetration depth control with a dual frequency ultrasonic system.

A novel ultrasound applicator for superficial simultaneous thermoradiotherapy consisting of two parallel-opposed linear arrays and a double-sided scanning reflector was constructed and tested for penetration depth control. In this design the arrays operate at different frequencies (1 and 5 MHz, in this study) and the input power to each array element (five 2 X 2 cm2 elements per array) is computer adjustable. The ultrasonic beams from the arrays are aimed at the scanning reflector which in turn deflects them simultaneously and in parallel toward the treatment volume. Relative intensity distributions generated by the prototype were measured in a degassed water phantom using a thermal technique for a selected reflector position; these showed that the ultrasonic intensity distribution can be controlled in the lateral dimensions by varying the input power level to individual array elements. A fixed-perfused canine kidney phantom was employed to demonstrate experimentally that real time penetration depth control is possible by varying the excitation magnitude of one array (frequency) relative to that of the other. It is concluded that the dual-frequency scanned-reflected ultrasound applicator offers a degree of dynamic three-dimensional control of the power deposition pattern of clinical significance.

Animals↗
PubMed1999

Existing antilisterial immunity does not inhibit the development of a Listeria monocytogenes-specific primary cytotoxic T-lymphocyte response.

Infection of BALB/c mice with Listeria monocytogenes stimulates an antilisterial immune response evident by the appearance of H2-Kd-restricted CD8(+) cytotoxic T lymphocytes (CTLs) specific for the nanomer peptides amino acids (aa) 91 to 99 of listeriolysin O (LLO 91-99) and aa 217 to 225 of the p60 molecule (p60 217-225). We have introduced point mutations at anchor residues within LLO 91-99 (92F) or p60 217-225 (218F), and BALB/c mice infected with L. monocytogenes strains containing these point mutations do not develop CTLs specific for LLO 91-99 or p60 217-225, respectively. We have used these strains to test whether primary CTL responses against L. monocytogenes-derived determinants can be stimulated within an environment of existing antilisterial immunity. We found that the development of a primary L. monocytogenes-specific CTL response is not altered by existing immunity to L. monocytogenes. For example, primary immunization with the p60 218F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of p60 217-225-specific CTLs at primary response levels and LLO 91-99-specific effectors at levels consistent with a memory CTL response. Similarly, primary immunization with the 92F strain of L. monocytogenes followed by a secondary immunization with wild-type L. monocytogenes results in stimulation of LLO 91-99-specific CTLs at primary response levels and p60 217-225-specific effectors at levels consistent with a memory CTL response. These results provide additional support for the use of L. monocytogenes as a recombinant vaccine vector and show that antivector immunity does not inhibit the development of a primary CTL response when the epitope is delivered by L. monocytogenes as the vaccine strain.

Amino Acid Substitution↗