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Biomedical subjects

J Lacy

Publications and source records attributed to J Lacy.

At least 19 recordsLinked to original sources
PubMed2001

Antisense to the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) sensitizes EBV-immortalized B cells to transforming growth factor-beta and chemotherapeutic agents.

The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) is absolutely required for EBV transformation of B cells. LMP-1 mimics a constitutively activated receptor of the tumor necrosis factor receptor family, mediating diverse oncogenic functions that influence growth, differentiation and susceptibility to apoptosis. Given the critical functions of LMP-1 in EBV-associated transformation, it represents a rational therapeutic target for modulation. We used antisense oligodeoxynucleotides targeted to LMP-1 as a strategy to suppress LMP-1 expression and thereby inhibit its functions. In previous studies, we have shown that short-term treatment of EBV-positive lymphoblastoid cell lines (LCLs) with LMP-1 antisense oligodeoxynucleotides can dramatically reduce levels of LMP-1 protein in association with inhibition of proliferation, stimulation of apoptosis, down-regulation of Bcl-2 and Mcl-1 and enhanced sensitivity to the chemotherapeutic agent, etoposide. Here, we provide further evidence of the profound effects of reducing LMP-1 levels using antisense oligodeoxynucleotides in EBV-transformed B cells. We have shown that LMP-1 antisense treatment of LCLs partially restores sensitivity to the anti-proliferative and apoptotic effects of transforming growth factor-beta, a potent negative regulator of normal human B-cell growth, in association with a reduction in cyclin D2 levels. In addition, LMP-1 antisense sensitizes LCLs to chemotherapeutic drugs from diverse classes, including etoposide, vincristine and dexamethasone, by enhancing apoptotic cell death. Finally, the anti-proliferative and apoptotic effects of LMP-1 antisense treatment were observed not only in laboratory-derived LCLs, but also in an EBV-positive cell line derived from an AIDS-related lymphoma. These studies demonstrate that antisense targeting of LMP-1 represents a rational therapeutic strategy for EBV-positive lymphoproliferative disorders.

Antineoplastic Agents, Hormonal↗
PubMed2001

Interferon beta-1a in children with multiple sclerosis is well tolerated.

BACKGROUND: Multiple sclerosis is a chronic demyelinating disease rare in children. Currently marketed disease modifying therapies are limited to adults. OBJECTIVE: To determine the tolerability of interferon beta-1a (IFNB-1 a) 30 mcg injected intramuscularly once a week in children with clinically definite relapsing-remitting multiple sclerosis (RRMS). DESIGN/METHODS: A standardized questionnaire was sent to neurologists in the United States to determine the tolerability of IFNB-1 a in patients younger than 16 years. RESULTS: Tolerability data were available for 9 of 33 children who were reported to initiate IFNB-1 a. Mean age on initiating treatment was 12.7 years (range 8 - 15) and mean duration of therapy was 17 months (range 5 - 36). No patient discontinued therapy due to an adverse event. CONCLUSIONS: Preliminary data indicate that weekly intramuscular injections of IFNB-1 a are well tolerated.

Adjuvants, Immunologic↗
PubMed2000

Bcl-2 antisense oligodeoxynucleotide therapy of Epstein-Barr virus-associated lymphoproliferative disease in severe combined immunodeficient mice.

Bcl-2 is upregulated by Epstein-Barr virus (EBV) in immortalized lymphoblastoid (LCL) B cells and is expressed in the majority of EBV-associated posttransplant lymphoproliferative disorders (PTLDs). Given the antiapoptotic function and chemoprotective effects of Bcl-2, it represents a rational target for modulation using antisense oligodeoxynucleotides in Bcl-2-expressing, EBV-associated lymphoproliferative disorders. Using a fully phosphorothioated oligodeoxynucleotide targeted to the first six codons of Bcl-2, we examined the effects of Bcl-2 antisense both in vitro in LCLs and in vivo in the human/severe combined immunodeficient chimeric model of EBV-associated lymphoproliferative disorders. In vitro treatment of LCLs with Bcl-2 antisense in the presence of cationic lipid was associated with decreased expression of Bcl-2 protein, inhibition of proliferation, and stimulation of apoptotic cell death; these effects were sequence-dependent. Furthermore, treatment of LCL-bearing severe combined immunodeficient mice with Bcl-2 antisense but not control oligodeoxynucleotides completely prevented or significantly delayed the development of fatal EBV-positive lymphoproliferative disease in vivo. These studies demonstrate that Bcl-2 antisense oligodeoxynucleotides mediate sequence-dependent antitumor effects in EBV-associated B-cell lymphoproliferations both in vitro and in vivo. These findings suggest that Bcl-2 antisense therapy may represent a novel antitumor treatment strategy for EBV-associated PTLDs and other Bel-2-expressing, EBV-positive malignancies.

Animals↗
PubMed2000

Decreased left ventricular ejection fraction in transgenic mice expressing mutant cardiac troponin T-Q(92), responsible for human hypertrophic cardiomyopathy.

The causality of mutant sarcomeric proteins in hypertrophic cardiomyopathy (HCM) is well established. The current emphasis is to elucidate the pathogenesis of HCM in transgenic animal models. We determined the left ventricular ejection fraction (LVEF) in transgenic mice expressing mutant cardiac troponin T (cTnT)-Q(92), known to cause HCM in humans. Transgenes were constructed by placing wild-type (R(92)) or mutant (Q(92)) full-length human cTnT cDNAs 3' into a 5.5-kb murine [alpha -myosin heavy chain (MyHC)] promoter injected into fertilized zygotes. Three wild-type and six mutant lines were produced. Transgene mRNA and proteins, detected using transgene-specific probes were expressed at high levels in all wild-type and three mutant lines. The total cTnT mRNA pool was increased by up to five-fold in transgenic mice, but the total cTnT protein remained unchanged. The mean values of LVEF, determined by(178)Ta radionuclide angiography, were 57.8+/-6% (n=4) in non-transgenic littermate (NLM), 53.3+/-10 (n=6) in wild-type and 39. 4+/-6 (n=5) in mutant transgenic mice (P=0.009). The heart/body weight ratios and the number of cells stained with terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling were similar among the groups. Three mutant mice had myocyte disarray and excess interstitial collagen and two had normal myocardial structure despite having reduced LVEF. Thus, in vivo expression of the mutant cTnT-Q(92)protein, responsible for human HCM, impaired global cardiac systolic function in transgenic mice, which also occurred in the absence of myocyte disarray and increased interstitial collagen.

Animals↗
PubMed2000

Oxysterols: 27-hydroxycholesterol and its radiolabeled analog.

We describe a convenient and stereoselective route to the synthesis of 27-hydroxycholesterol. Also its radiolabeled analog, 22, 23 di [(3)H]-27-hydroxycholesterol with high specific radioactivity (55 Ci/mmol) was synthesized by this method. Julia condensation of steroidal 22-sulfone with aldehyde, led to the addition of the 23-27 carbon side chain building block to the steroid backbone. Formed in this reaction beta-hydroxysulfone moiety was reduced by sodium amalgam generate 22-23 unsaturated bond. Further reduction either by hydrogen or tritium furnished substrates for the synthesis of title compounds.

Chromatography, High Pressure Liquid↗
PubMed1998

Antisense to the epstein-barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) suppresses LMP-1 and bcl-2 expression and promotes apoptosis in EBV-immortalized B cells.

The Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP-1) is required for viral transformation and functions to protect cells from apoptotic cell death, in part, by induction of antiapoptotic genes, including Bcl-2 and A20. We have used antisense oligodeoxynucleotides targeted to LMP-1 as a strategy to suppress LMP-1 expression and thereby inhibit its functions. We have shown that levels of LMP-1 protein in EBV-positive lymphoblastoid cell lines can be reduced by in vitro treatment with unmodified oligodeoxynucleotides targeted to the first five codons of the LMP-1 open-reading frame. Furthermore, suppression of LMP-1 was associated with molecular and phenotypic effects that included downregulation of the LMP-1-inducible antiapoptotic genes, Bcl-2 and Mcl-1, inhibition of proliferation, stimulation of apoptosis, and enhancement of sensitivity to the chemotherapeutic agent, etoposide. These effects were largely sequence-specific and observed in EBV-positive, but not EBV-negative cell lines. These studies suggest that lowering expression of LMP-1 in EBV-associated malignancy might have therapeutic effects and might synergize with other antitumor agents.

Apoptosis↗
PubMed1998

Human biodistribution and dosimetry of the PET perfusion agent copper-62-PTSM.

UNLABELLED: Copper-62-pyruvaldehyde bis(N4-methyl)thiosemicarbazone (PTSM) has been proposed as a generator-produced radiopharmaceutical for perfusion imaging using PET. Several clinical studies have demonstrated the ability of 62Cu-PTSM to quantitate myocardial and cerebral perfusion in humans. Because 62Cu-PTSM is generator-produced, it can be provided to clinical centers without cyclotron availability and, therefore, represents a cost-effective, practical PET perfusion tracer for clinical applications. To assess the safety, time-dependent biodistribution, and whole-body and organ-specific absorbed radiation dose estimates of this tracer, a Phase I study of 62Cu-PTSM was performed using whole-body imaging with PET in 10 healthy volunteers and with the radiopharmaceutical delivered by a compact modular generator unit. METHODS: Five male and five female subjects underwent a series of clinical tests and head-to-midthigh, whole-body PET scans at three time points over 1 hr after intravenous injection of 62Cu-PTSM. Before injection of the tracer, PET transmission scans were performed and used to correct the emission data for attenuation. Final image data were expressed in units of mCi/cc. Using standard organ weights, the percent injected dose per organ was calculated. Biodistribution data were obtained at three different time points and from these data biological half-lives in different organs were determined for calculation of radiation absorbed dose estimates. RESULTS: The liver was seen as the critical organ receiving a dose of 0.0886 rad/mCi. This organ defined the maximum single injected dose at 56 mCi using the limit of 5 rads to a critical organ per study per year. The whole-body dose is 0.0111 rad/mCi, resulting in a 0.622 rad exposure with a maximum single injection dose. Only trace levels of activity were found in the urine, which suggests low levels of urinary excretion and bladder exposure. No significant clinical, electrocardiographic or laboratory abnormalities were seen after the injection of 62Cu-PTSM. CONCLUSION: Copper-62-PTSM is a clinically safe radiopharmaceutical with favorable dosimetry for human studies at injected doses significantly above those projected for use in clinical studies.

Adult↗
PubMed1997

Regulation of the human IgE receptor (Fc epsilonRII/CD23) by Epstein-Barr virus (EBV): Ku autoantigen binds specifically to an EBV-responsive enhancer of CD23.

An early and critical event in immortalization of human B cells by Epstein-Barr virus (EBV) is induction of CD23 expression. CD23 is constitutively expressed in all EBV-immortalized B cells and its expression is tightly linked with immortalization. We have previously shown that activation of CD23 by EBV occurs at the transcriptional level and is mediated, in part, by EBV-responsive enhancer elements in the region of the type a promoter. We have localized one EBV-responsive enhancer (designated EBVRE) to a 37 bp sequence in intron 1 of type a CD23 that contains a GC-rich sequence that binds nuclear protein(s) from EBV-positive but not EBV-negative cells with sequence specificity. This EBVRE-binding activity was enhanced by protein phosphorylation and did not react with antibodies to the ubiquitous GC box transcription factor, Sp1. We have now shown by protein purification with peptide sequencing and immunological reactivity that p70/p80 Ku autoantigen [the DNA-binding component of DNA-dependent protein kinase (DNA-PK)] binds to this EBVRE with high affinity and sequence specificity. Although Ku autoantigen is ubiquitously expressed, an EBV-specific DNA-protein complex that contains Ku was elicited from EBV-positive but not EBV-negative nuclear extracts. Furthermore, the formation of this EBV-specific DNA-Ku complex was dramatically enhanced by protein phosphorylation. Thus, we have identified EBVRE-binding activity that contains the Ku autoantigen, is DNA sequence specific and is present in EBV-positive but not EBV-negative nuclear extracts. The possible functional significance of the Ku autoantigen-EBVRE interaction is discussed in light of the role of DNA-PK in phosphorylation and activation of several transcription factors. We suggest that phosphorylation of the EBV-specific EBVRE-binding activity by DNA-PK may modulate its activity as a transcription factor.

Amino Acid Sequence↗
PubMed1996

Variations in the natural history and survival of patients with supratentorial low-grade astrocytomas.

Data from 55 consecutive patients with low-grade astrocytomas treated between 1982 and 1990 were analyzed to determine specific outcome factors, including time to recurrence, incidence of anaplastic transformation, and survival. Gender, type of symptoms, contrast enhancement, and timing of radiation therapy were not significant in determining outcome. Patients who had symptoms for > 2 years and underwent gross-total resection of the tumor, with age as a continuous variable, were associated with significantly longer time to recurrence and survival. Within the population of patients with low-grade astrocytomas, patients with chronic epilepsy clearly had the best prognoses. There were no tumor recurrences or deaths in 27 patients with chronic epilepsy, regardless of the extent of surgery and without the use of radiotherapy. Ten-year survival was 100% for 31 patients who underwent gross-total tumor resection, regardless of the length of preoperative symptoms. Immediate postoperative radiotherapy did not prolong the time to recurrence, reduce the incidence of transition to more malignant tumors at recurrence, or increase the length of survival when compared with delayed radiotherapy. Because recurrence with a high-grade lesion caused 92% of the mortality in our series, the benefit in patients who underwent aggressive surgery seems to result from a significant decrease in the risk of recurrence when compared with patients who underwent anything less than gross-total resection. Our data also suggest that variability in the natural history of low-grade astrocytomas has a strong influence in determining survival and that tumors associated with chronic epilepsy are much less likely to become more malignant over time.

Adult↗
PubMed1996

Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.

Adult↗
PubMed1994

Regulation of the human IgE receptor (Fc epsilon RII/CD23) by EBV. Localization of an intron EBV-responsive enhancer and characterization of its cognate GC-box binding factors.

EBV infection of human B lymphocytes induces expression of the low affinity IgE receptor, Fc epsilon RII/CD23. CD23 is constitutively expressed in EBV-immortalized B cells and may play an essential role in immortalization. We previously explored the regulation of CD23 by EBV, showing that induction results from transcriptional activation that is mediated, in part, by an EBV-responsive transcriptional regulatory element in the 5' region of CD23 (-229 to +305 relative to the type a promoter). We now report the localization of the regulatory element and characterization of its cognate DNA-binding proteins. Reporter gene assays in EBV-positive and -negative lines localized a functional EBV-responsive enhancer to a 37-bp fragment (+248 to +284) that contains a GC-rich sequence (GC box) within intron I of type a CD23. This fragment was shown by mobility shift assays to specifically bind nuclear protein(s) from EBV-positive lines, but not EBV-negative lines. Mutation of the GC box resulted in a loss of protein-binding activity, implicating involvement of a GC box-binding protein in the DNA/protein interaction. Supershift assays suggested that the ubiquitous GC box-binding transcription factor, Sp1, is not a part of the complex, and UV-crosslinking studies demonstrated that the DNA/protein complex contains at least two proteins that differ in size from other known GC box-binding proteins. Binding of these proteins to the enhancer element requires phosphorylation, because phosphatase treatment of nuclear extracts abolished formation of the DNA/protein complex. These studies reveal the presence of an EBV-responsive enhancer element in intron I of type a CD23 and implicate a GC box-binding transcription factor in the activation of CD23 by EBV.

Base Sequence↗
PubMed1994

Epstein-Barr viral nuclear antigen 1 antisense oligodeoxynucleotide inhibits proliferation of Epstein-Barr virus-immortalized B cells.

The Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1) is a latent viral protein that is expressed in all EBV-immortalized lymphocytes and plays an essential role in immortalization y EBV. EBNA-1 protein is required for replication and maintenance of the episomal viral genome in latently infected, immortalized cells. Given the essential function of EBNA-1 in immortalization, we have examined the effect of EBNA-1 antisense oligodeoxynucleotides on expression of EBNA-1 protein and proliferation in EBV-immortalized lymphoblastoid cells. We have shown that exposure to unmodified antisense oligodeoxynucleotide of codons 6 through 10 of EBNA-1 partially suppressed EBNA-1 protein expression in EBV-immortalized lymphoblastoid cells relative to untreated cells or cells exposed to two scrambled sequences of the EBNA-1 antisense. Furthermore, EBNA-1 antisense inhibited proliferation of EBV-immortalized cells by at least 50% compared with the scrambled antisense sequences. There was no difference in the effect of antisense and scrambled antisense oligodeoxynucleotides on the proliferation of EBV-negative cells, indicating that the antiproliferative effect of EBNA-1 antisense was EBV-specific. These findings underscore the essential role of EBNA-1 in immortalization and, furthermore, have potential therapeutic implications for EBV-associated neoplastic diseases.

Adult↗
PubMed1993

Perinatal clinical epidemiology.

A literature search of personal files, the Oxford Database of Perinatal Trials, Medline, and the Research Update databases, identified 19 perinatal trials published between October 1991 and September 1992. Included were only those trials in which the efficacy or effectiveness of an antenatal intervention was assessed by a neonatal outcome. A quality assessment of each study was performed. Quality scores ranged from 0.25 to 0.80 (maximum possible score, 1.00). Most trials did not show a statistically significant change in the primary outcome measure, because of an overestimate of the treatment effect on which the sample size had been based. Thus, clinically important treatment effects often may be overlooked. None of these trials on their own showed beyond doubt whether the intervention under study did more good than harm. There is a need to base sample size calculations on more realistic, but still clinically important, event rate differences to show the effectiveness of perinatal interventions aimed at improving neonatal outcomes. To do so usually requires a large sample size, necessitating multicenter trials with national and international cooperation.

Female↗
PubMed1993

PDGF-induced Egr-1 expression in rat mesangial cells is mediated through upstream serum response elements.

Platelet-derived growth factor (PDGF) has been implicated in the process of mesangial cell (MC) proliferation in vitro and in vivo. To investigate early changes in gene expression that couple biochemical events with changes in phenotype in PDGF-stimulated cultured MC, we studied expression of the early growth response gene 1 (Egr-1), a member of the family of immediate early genes. Our findings show that protein tyrosine phosphorylation is required for induction of Egr-1 mRNA and proliferation by PDGF in MC. Nuclear run-off assays show that Egr-1 induction occurs at the transcriptional level. An 11.3-fold increase in Egr-1 transcription rate was observed as early as 5 min after PDGF stimulation of MC. Promoter deletion analysis revealed that the region critical for Egr-1 inducibility by PDGF contains serum response element (SRE) consensus sequences. Sequential deletion of the Egr-1 SREs led to a stepwise drop in promoter activity, suggesting that PDGF induces Egr-1 transcription through SREs in the Egr-1 promoter region. Interestingly, electrophoretic mobility shift assays, with an Egr-1 SRE as probe, demonstrate that protein-SRE complexes of differing size undergo modest quantitative changes following PDGF stimulation. These data in MC suggest that the upstream SREs mediate the transcriptional induction of Egr-1 by PDGF.

Animals↗
PubMed1993

Nutrition management of the hepatic transplant patient.

Patients who are candidates for liver transplantation are predisposed to severe nutritional depletion because of their underlying hepatic dysfunction. Nutrition-associated complications, particularly infection and poor wound healing, are common causes of morbidity and mortality among adults with chronic liver disease and malignancy who are referred for liver transplantation. During the preoperative period, maintenance or repletive nutrition is provided to the patient with hepatic failure. The patient's postoperative period is characterized by the catabolic response to a major operation, the progressive improvement of hepatic graft function, and the persistent compensatory renal abnormalities that are associated with liver failure. The nutrition management of the patient with liver failure has been well described. Nutrition intervention during the intraoperative and postoperative periods remains enigmatic. The following case report describes the nutrition management of a liver transplant recipient in the intraoperative and postoperative periods.

Blood Proteins↗
PubMed1993

Extreme immaturity: outcome of 568 pregnancies of 23-26 weeks' gestation.

OBJECTIVE: To provide guidelines to the perinatologist regarding extremely premature infants based on the experience of the University of Toronto Newborn Service (two high-risk perinatal units and one outborn neonatal intensive care unit), with a catchment area of 60,000 deliveries annually. METHODS: The study included all births or admissions in the Newborn Service from January 1, 1982 to June 30, 1987 with gestational age determined by the best obstetric estimate of gestational age, ranging from 23-26 completed weeks. The obstetric records were reviewed and the surviving infants followed prospectively for a minimum of 2 years after delivery. RESULTS: Analysis of the neonatal and 2-year follow-up data on 568 infants born between 23-26 weeks' gestation revealed a 39% mortality rate, which increased with decreasing gestation. The highest mortality rates occurred following complicated pregnancies, including fetal growth restriction. Intact survival increased with increasing gestational age, from 11% at 23 weeks to 50% at 26 weeks. There was a marked improvement in both mortality and morbidity by 25 completed weeks. CONCLUSIONS: The results suggest that an aggressive approach before 24 completed weeks' gestation is not warranted. From a total of 60,000 live births per year, only one child born at 23 weeks' gestation and three at 24 weeks were free of major handicap at 2 years.

Birth Weight↗
PubMed1992

Transcriptional regulation of the human IgE receptor (Fc epsilon RII/CD23) by EBV. Identification of EBV-responsive regulatory elements in intron 1.

EBV infection of B cells induces the B cell activation Ag, CD23 (Fc epsilon RII). CD23 remains constitutively expressed at high levels in all EBV-immortalized B cells and likely plays an important role in the initiation and maintenance of immortalization by EBV. By utilizing an EBV-negative Burkitt's lymphoma line (BJAB) and EBV-positive sublines derived from it by in vitro infection, we have examined the molecular mechanisms involved in the regulation of CD23 by EBV. By nuclear runoff analysis, we have found that induction of CD23 is mediated by transcriptional activation that occurs in the presence of the transformation-competent B958 virus but not in the presence of the nontransforming P3HR-1 strain of EBV. To identify EBV-responsive transcriptional regulatory elements of CD23, we have performed reporter gene assays using plasmids containing fragments of the CD23 gene derived from its 5' terminus and adjacent flanking region transfected into EBV-positive and -negative BJAB lines. We have identified a 534-bp fragment of the gene which enhances transcription from a heterologous promoter (SV40) and reporter gene (chloramphenicol acetyltransferase) only in the presence of transformation-competent strains of EBV. Deletion of 144 bp of intron 1 from the 3' end of this fragment results in loss of EBV-responsive enhancer activity. The finding of an EBV-responsive enhancer element of CD23 is supported by mobility shift assays that demonstrated the formation of specific DNA-protein complexes between nuclear protein from transforming EBV-positive cells and the 144-bp intron sequence. These studies suggest that the transcriptional activation of CD23 by transforming strains of EBV involves regulatory elements that are located within the first intron of the gene.

Antigens, Differentiation, B-Lymphocyte↗