Inverse proportions of activated and CD4 circulating lymphocytes in AIDS patients.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Biomedical subjects
J C Lefebvre
Publications and source records attributed to J C Lefebvre.
Cloning, mapping, and genomic organization of the LSLCL gene, encoding a new lymphocytic secreted mucin-like protein with a C-type lectin domain: A new model of exon shuffling.
Explore the source record for details and available documents.
Chromosome Mapping↗
The relationship of arthritis self-efficacy to daily pain, daily mood, and daily pain coping in rheumatoid arthritis patients.
There is an increasing awareness in the medical community that psychosocial variables such as beliefs in self-efficacy are important determinants of treatment outcome. However, before measures of self-efficacy are widely incorporated into clinical practice, there needs to be a better understanding of how they relate to daily pain, mood and coping. In the present study 128 rheumatoid arthritis patients completed diaries for 30 days in which they provided daily ratings of joint pain, negative and positive mood, the use of pain coping strategies, and coping efficacy. The patients then participated in an evaluation session during which measures of self-efficacy (the Arthritis Self Efficacy Scale (ASES)), demographic variables, and medical status were collected. A series of hierarchical regression analyses was conducted to determine the degree to which self-efficacy measures collected at the time of the evaluation session were related to daily diary measures collected during the 30 preceding days. The results revealed that self-efficacy was significantly related to daily ratings of pain, mood, coping and coping efficacy. Interestingly, the findings regarding self-efficacy were obtained even after taking into account the effects of important demographic and medical status variables. Taken together, these results suggest that self-efficacy ratings collected from arthritis patients at the time of an evaluation session may well be related to recent experiences of daily pain and mood, as well as the daily use and perceived effectiveness of pain coping strategies.
Activities of Daily Living↗
Secreted phospholipases A(2), a new class of HIV inhibitors that block virus entry into host cells.
Mammalian and venom secreted phospholipases A(2) (sPLA(2)s) have been associated with a variety of biological effects. Here we show that several sPLA(2)s protect human primary blood leukocytes from the replication of various macrophage and T cell-tropic HIV-1 strains. Inhibition by sPLA(2)s results neither from a virucidal effect nor from a cytotoxic effect on host cells, but it involves a more specific mechanism. sPLA(2)s have no effect on virus binding to cells nor on syncytia formation, but they prevent the intracellular release of the viral capsid protein, suggesting that sPLA(2)s block viral entry into cells before virion uncoating and independently of the coreceptor usage. Various inhibitors and catalytic products of sPLA(2) have no effect on HIV-1 infection, suggesting that sPLA(2) catalytic activity is not involved in the antiviral effect. Instead, the antiviral activity appears to involve a specific interaction of sPLA(2)s to host cells. Indeed, of 11 sPLA(2)s from venom and mammalian tissues assayed, 4 venom sPLA(2)s were found to be very potent HIV-1 inhibitors (ID(50) < 1 nM) and also to bind specifically to host cells with high affinities (K(0.5) < 1 nM). Although mammalian pancreatic group IB and inflammatory-type group IIA sPLA(2)s were inactive against HIV-1 replication, our results could be of physiological interest, as novel sPLA(2)s are being characterized in humans.
Animals↗
T cells chronically infected with HIV do not contain sufficient Nef to promote CD4 downmodulation in the absence of envelope-mediated effects.
Among HIV viral proteins, envelope glycoproteins and Nef have been both suggested to participate in CD4 downregulation during the course of HIV infection. In a previous study, we provided evidence that a mutant form of CD4 that does not bind gp120 was never downregulated in chronically HIV-1- and HIV-2-infected CEM cells. To further investigate the relative effects of Nef or glycoproteins in CD4 downregulation, recombinant vaccinia virus (VV) vectors were used to express high levels of HIV-1 viral proteins in cells expressing both wild-type and mutant CD4. It was demonstrated that during HIV infection, overexpression of Nef, achieved through the VV expression system, was necessary to induce CD4 downregulation in the mutant CD4-expressing cell model. These results are consistent with the hypothesis that Nef-mediated CD4 downregulation depends on the cellular levels of Nef expression. We concluded that during the late stage of viral replication, CD4 downregulation is mostly due to gp120 and not to Nef because of a low level of Nef expression.
CD4 Antigens↗
Molecular cloning of a new secreted sulfated mucin-like protein with a C-type lectin domain that is expressed in lymphoblastic cells.
We have previously demonstrated hyposialylation of the two major CD45 and leukosialin (CD43) molecules at the surface of latently human immunodeficiency virus type 1-infected CEM T cells (CEMLAI/NP), (Lefebvre, J. C., Giordanengo, V., Doglio, A., Cagnon, L., Breittmayer, J. P., Peyron, J. F., and Lesimple, J. (1994) Virology 199, 265-274; Lefebvre, J. C., Giordanengo, V., Limouse, M., Doglio, A., Cucchiarini, M., Monpoux, F., Mariani, R., and Peyron, J. F. (1994) J. Exp. Med. 180, 1609-1617). Searching to clarify mechanism(s) of hyposialylation, we observed two sulfated secreted glycoproteins (molecular mass approximately 47 and approximately 40 kDa) (P47 and P40), which were differentially sulfated and/or differentially secreted in the culture supernatants of CEMLAI/NP cells when compared with parental CEM cells. A hybridoma clone (7H1) resulting from the fusion between CEMLAI/NP and human embryonic fibroblasts MRC5 cells produced very large amounts of P47 that was purified using Jacalin lectin (specific for O-glycans) and microsequenced. Cloning of P47 was achieved using a CEMLAI/NP cDNA library screened with a degenerate oligonucleotide probe based on its NH2-terminal amino acid sequence. A single open reading frame encoding a protein of 323 amino acids was deduced from the longest isolated recombinant (1.4 kilobase). P47 is a secreted sulfated protein. It carries an NH2-terminal RGD (Arg-Gly-Asp) triplet, a striking alpha-helical leucine zipper composed of six heptads, and a C-terminal C-type lectin domain. The NH2-terminal portion is rich in glutamic acids with a predicted pI of 3.9. In addition, a hinge region with numerous condensed potential sites for O-glycan side chains, which are also the most likely sulfation sites, is located between the RGD and leucine zipper domains. Transcripts were detected in lymphoid tissues (notably bone marrow) and abundantly in T and B lymphoblastoid but very faintly in monocytoid cell lines.
Amino Acid Sequence↗
Hepatitis G and C viruses respond to interferon-alpha with different virologic kinetics.
The aim of this work was to specify the time course of response to interferon (IFN) of hepatitis G virus (HGV) and hepatitis C virus (HCV) in coinfected individuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C, was screened for the presence of both HGV and HCV RNAs to select seven coinfected patients. Spontaneous recovery from HGV infection was excluded through the detection of antibodies to the envelope-2 protein of HGV and HCV isolates were genotyped. Within three months of treatment, we found that HGV RNA was transiently cleared in 6/7 patients, but the rate of long-term favorable response was very low (1/7). In addition, considering the same individuals separately, it was shown that HGV and HCV responded to IFN with different kinetics in 5/7 patients. Taken together, these results underscore the importance of the virological basis of the resistance to IFN treatment.
Antiviral Agents↗
3'-End modification of the adenoviral VA1 gene affects its expression in human cells: consequences for the design of chimeric VA1 RNA ribozymes.
Polymerase III (pol III)-dependent genes, like the adenoviral VA1 gene, are of particular interest for expressing small therapeutic RNAs into cells. A new VA1 RNA carrier molecule was generated through the deletion of the VA1 RNA central domain to give rise to the VAdeltaIV RNA vector that was devoid of undesirable physiologic activity (i.e., inhibition of the interferon-induced protein kinase, PKR). This vector was used to express in human cells hammerhead ribozymes targeted against the human immunodeficiency virus (HIV). Eight anti-HIV ribozymes were inserted at the 3'-end of this vector immediately before the four T-residues that serve as a transcription termination signal. Although the constructs were active in vitro, they failed to inhibit HIV replication in transient assays. Analysis of the intracellular ribozyme expression in cells revealed several anomalies. First, using mutant derivatives, we showed that the presence of two or three consecutive T-residues in the ribozyme portion was sufficient to promote the release of anomalous short transcripts. Second, when the ribozyme did not contain T-rich sequence, full-length transcripts were produced, but these transcripts were very unstable and were retained in the cell nucleus. In contrast, insertion of the ribozyme in place of the central domain of VA1 RNA led to production of full-length transcripts that were stable and located in the cytoplasm but that were not found to be active in vitro. Taken together, these results have important consequences for the future design of active intracellular ribozymes based on the use of pol III-transcribed genes.
3' Untranslated Regions↗
Social context of pain in children with Juvenile Primary Fibromyalgia Syndrome: parental pain history and family environment.
OBJECTIVE: The purpose of this study was to describe parental pain history and the family environment as it relates to the functional status of children with Juvenile Primary Fibromyalgia Syndrome (JPFS). DESIGN AND OUTCOME MEASURES: Twenty-nine parents of children with JPFS completed a pain history questionnaire, Von Korff Chronic Pain Grading system, and the Family Environment Scale (FES). Twenty-one adolescents with JPFS completed the FES, the Visual Analogue Scale for Pain, the modified Fibromyalgia Impact Questionnaire for Children, the Arthritis Impact Measurement Scales, and the Symptom Checklist-90-Revised. Correlational analyses were performed. RESULTS: Parents of children with JPFS reported multiple chronic pain conditions, including but not limited to fibromyalgia. Parental pain history and the family environment correlated with the health status of adolescents with JPFS. Children with JPFS perceived the family environment as significantly more cohesive than did their parents. Greater incongruence between parent and child responses on the FES positively correlated with greater impairment. CONCLUSIONS: These results suggest that family environment and parental pain history ày be related to how children cope with JPFS. Behavioral interventions targeting the family may improve the long-term functional status of children with JPFS.
Adolescent↗
Cloning and expression of cDNA for a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase from the CEM T-cell line.
Complementary DNA encoding a human Gal(beta1-3)GalNAc alpha2,3-sialyltransferase type II (hST3Gal II) was cloned from a CEM T-cell cDNA library using a 23-base oligonucleotide probe. The sequence of this probe was established on the basis of a slightly divergent sialylmotif L that was obtained by polymerase chain reaction with degenerate oligonucleotide primers based on the conserved sialylmotif L of mammalian Gal(beta1-3)GalNAc alpha2,3-sialyltransferases. It was thus confirmed that a short oligonucleotide probe may be sensitive and highly specific. The nucleotide and amino acid sequences of hST3Gal II show, respectively, 56.3% and 49.3% similarity to hST3Gal I [Kitagawa, H. & Paulson, J. C. (1994) J. Biol. Chem. 269, 17872-17878] and 88.1% and 93.7% similarity to murine ST3Gal II [Lee, Y. C., Kojima, N., Wada, E., Kurosawa, N., Nakaoka, T., Hamamoto, T. & Tsuji, S. (1994) J. Biol. Chem. 269, 10028-10033]. hST3Gal II mRNA was highly expressed in heart, liver, skeletal muscle and various lymphoid tissues but not in brain and kidney. A soluble form of hST3Gal II expressed in COS-7 cells was tested in vitro for substrate specificity and kinetic properties. Asialofetuin and asialo-bovine submaxillary mucin appeared better substrates for hST3Gal II than for its murine counterpart as previously reported [Kojima, N., Lee, Y.-C., Hamamoto, T., Kurosawa, N. & Tsuji, S. (1994) Biochemistry 33, 5772-5776]. In previous studies, we have shown hyposialylation of O-glycans attached to two major lymphocyte CD43 and CD45 cell surface molecules in human-immunodeficiency-virus-1(HIV-1)-infected T-cell lines. Since comparable levels of hST3Gal I and hST3Gal II mRNA and enzymatic activity were observed in parental and HIV-1-infected CEM T-cell lysates, the sialylation defect associated with HIV infection of this cell line is probably due to a mechanism different from a simple altered catalytic activity of these sialyltransferases.
Amino Acid Sequence↗
Self-efficacy for arthritis pain: relationship to perception of thermal laboratory pain stimuli.
OBJECTIVE: To examine how self-efficacy for arthritis pain relates to the perception of controlled laboratory pain stimuli. METHODS: Forty patients with osteoarthritis completed self-report measures of self-efficacy for arthritis pain. They then participated in a single experimental session in which measures of thermal pain threshold and tolerance were collected, as well as measures of the perceived intensity and unpleasantness of a range of thermal pain stimuli. RESULTS: Correlational analyses revealed that patients reporting high self-efficacy for arthritis pain rated the thermal pain stimuli as less unpleasant than those reporting low self-efficacy. When subjects scoring very high and very low in self-efficacy were compared, it was found that subjects scoring high on self-efficacy for arthritis pain had significantly higher pain thresholds and pain tolerance than those scoring low on self-efficacy. CONCLUSIONS: These results indicate that self-efficacy for arthritis pain is related to judgments of thermal pain stimuli. Implications for the understanding of arthritis pain and for future laboratory research are discussed.
Attitude to Health↗
Pain coping strategies and coping efficacy in rheumatoid arthritis: a daily process analysis.
Data from daily diaries were used to analyze pain coping processes in rheumatoid arthritis patients. For 30 consecutive days, 53 individuals described the pain coping strategies they used that day and rated the efficacy of their coping, joint pain, and positive and negative mood. Relations among variables were examined across-persons and within-persons over time. At the across-persons level of analysis, (i) daily coping efficacy was unrelated to pain coping or pain intensity, and (ii) the more frequent daily use of a wide variety of pain coping strategies was correlated with greater pain. Within-person analyses provided unique information about the relations among coping, pain, and mood not apparent in the across-persons results. Specifically, these analyses showed that increases in daily coping efficacy were not only related to decreases in pain, but also to decreases in negative mood and increases in positive mood. Time-lagged effects of coping and coping efficacy were also found. Individuals who reported high levels of coping efficacy on one day had lower levels of pain on the subsequent day. The daily use of pain reduction efforts and relaxation strategies also contributed to an improvement in next-day pain and an enhancement of positive mood. The implications of these findings for the assessment of pain and coping in rheumatoid arthritis patients are discussed.
Adaptation, Psychological↗
Altered sialylation of alveolar macrophages in HIV-1-infected individuals.
In previous studies, we have demonstrated that O-glycans at the surface of HIV-1-infected cell lines were hyposialylated. Moreover, we and others have shown that HIV+ individuals produced autoantibodies that react with hyposialylated CD43, on T cell lines. Since the autoantigen responsible for this abnormal immune response was not easily found in the peripheral blood cells of corresponding patients, we searched for its possible presence in other sites. Using fluorescence staining of alveolar macrophages with various lectins, we show that the binding of the PNA lectin specific for asialo O-glycans is much more efficient on cells from HIV-1-infected individuals. Moreover, the degree of reactivity of PNA is correlated with the clinical stage of the illness.
Adult↗
Alteration of CD44 expression in HIV type 1-infected T cell lines.
CD44 is known to interfere in HIV replication and to participate in many physiological processes such as lymphocyte binding to high endothelial venules of lymphoid tissue, lymph nodes, and mucosal endothelium. The T cell lines MOLT-4 and CEM, and CEM subclones were infected with the HIV-1 LAI strain and monitored for the expression of CD44 during the course of chronic virus production until the infected cells were at the stage of latent infection. The levels of CD44 protein expression were quantified using cell surface immunostaining and biotinylation. The maturation of CD44 molecules was evaluated by metabolic sulforadiolabeling and CD44 mRNA was visualized by Northern blot analysis. We show a downmodulation of CD44 expression in infected T cell lines and subclones. This phenomenon was most evident at the stage of latent infection. Then, CD44 molecules were undetectable at both the protein and mRNA levels in latently infected CEM cells and CEM subclones. In addition, the 97-kDa standard CD44 isoform showed a shift upward, while detectable during the stage of chronic virus production. In latently infected MOLT-4 cells, the CD44 protein levels were dramatically decreased; CD44 mRNA was detected, but the sizes differed from the mRNA in uninfected cells. Since CD44 is known to regulate in part lymphocyte homing and HIV replication, the alterations that were observed in the expression of this molecule could interfere with the particular homing of HIV-infected cells and/or viral latency.
Alternative Splicing↗
Pain coping strategies in children with juvenile primary fibromyalgia syndrome: correlation with pain, physical function, and psychological distress.
OBJECTIVES: The purpose of this study was twofold: 1) to describe the coping strategies used by children with juvenile primary fibromyalgia syndrome (JPFS), and 2) to examine how pain coping relates to measures of pain, disability/function, psychological distress, and pain behavior. METHODS: Sixteen children with JPFS completed the Child Version of the Coping Strategies Questionnaire (CSQ-C), the visual analog scale for pain, the McGill Pain Questionnaire, the Fibromyalgia Impact Questionnaire modified for children, the Arthritis Impact Measurement Scales 2, and the Symptom Checklist-90-Revised. Subjects also also underwent pain behavior observation. Pearson's product moment correlations were conducted to examine the relationship of coping to measures of pain and disability. RESULTS: The Pain Control and Rational Thinking composite factor score on the CSQ-C correlated with measures of pain severity, functional disability, and psychological distress. Results supported the internal reliability of the CSQ-C in assessing pain coping. CONCLUSIONS: These results suggest that the CSQ-C may provide a reliable measure for assessing variations in pain coping in JPFS patients. Behavioral interventions aimed at increasing the perception of pain control may be beneficial in treating JPFS.
Activities of Daily Living↗
[Viral load and antiretroviral treatments in children infected by human immunodeficiency virus].
Explore the source record for details and available documents.
Adolescent↗
Pain in young adults--III: Relationships of three pain-coping measures to pain and activity interference.
The study had two purposes: (a) to examine the relationships among coping strategies measured by the Coping Strategies Questionnaire (CSQ) (1), the Vanderbilt Pain Management Inventory (VPMI) (2), and the Ways of Coping Inventory (WOC) (3) and identify the higher-order composite factors representing these relationships; and (b) to determine the degree to which individual coping scale scores and composite coping factor scores could explain variability in the pain intensity and pain-related activity interference reported by young adults. Measures of pain coping were collected from 206 young adults using the CSQ, VPMI, and WOC, along with measures of pain intensity, pain location, and the extent to which pain interfered with daily activities. Results indicated considerable variability in the reported frequency of use of pain-coping strategies and in pain intensity, location, and activity interference. Principal components factor analysis identified three higher-order coping factors (Emotional and Other-Directed Coping, Active Cognitive Coping, and Self-Efficacy for Pain Control) that explained 87% of the variance in individual coping scale scores. The degree to which individual scale scores and composite factor scores explained variability in pain intensity and activity interference variables was determined through a series of multiple regression analyses. The results revealed that individual scale scores, particularly the CSQ scales of catastrophizing and praying or hoping, were best able to explain the variance in measures of pain and activity interference. Taken together, these findings provide further support for the importance of coping variables in explaining the experience of pain and adjustment in young adults.
Adaptation, Psychological↗
Autoantibodies directed against CD43 molecules with an altered glycosylation status on human immunodeficiency virus type 1 (HIV-1)-infected CEM cells are found in all HIV-1+ individuals.
Autoantibodies to lymphocytes have been detected in sera from human immunodeficiency virus type 1 (HIV-1)-infected individuals, and several autoantigens have been described. Among them, hyposialylated CD43 has been shown to be a target for autoantibodies in up to 47% of HIV+ individuals. However, the corresponding autoantigen (ie, the incompletely sialylated CD43) has not been isolated from blood cells of HIV-1-infected individuals. Recently, we have observed in vitro that HIV-1 productively or latently infected CEM cells (CEMLAI/NP) express CD43 molecules with modified glycosylation (mogly CD43). Using CEMLAI/NP cells, which do not express any structural viral antigen, we show now that all of the tested HIV+ sera from asymptomatic individuals, and up to 86% of those from subjects at the acquired immunodeficiency syndrome stage contain antibodies (mainly IgM and, to a lesser degree, IgG) that recognize the surface of CEMLAI/NP cells, and precipitate mogly CD43 molecules from the cells lysates. Taken together with our previous demonstration of altered glycosylation of CD43 from HIV-1-infected CEM cells in vitro, the constant antimogly CD43 autoimmune response observed from asymptomatic HIV-1+ subjects is likely to illustrate the occurrence of an altered glycosylation in vivo of the major lymphocyte surface CD43 glycoprotein, associated with HIV-1 infection.
Acquired Immunodeficiency Syndrome↗