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Biomedical subjects

J C Lefebvre

Publications and source records attributed to J C Lefebvre.

At least 19 recordsLinked to original sources
PubMed2003

Sclerosing peritonitis: report of three cases.

Sclerosing peritonitis is a dramatic complication of continuous ambulatory peritoneal dialysis and chronic peritoneal inflammation. Both visceral and parietal surfaces of the peritoneal cavity are involved. A thickened peritoneum encloses the small intestine in a "cocoon" formation which often leads to intestinal occlusion. CT scan may help obtaining an early diagnosis but diagnosis is often established with some delay or even at the time of laparotomy. Our report describes three cases of this uncommon peritoneal fibrosis syndrome which caused intestinal obstruction requiring surgical intervention.

Adult↗
PubMed2001

Terminal minihelix, a novel RNA motif that directs polymerase III transcripts to the cell cytoplasm. Terminal minihelix and RNA export.

Determining the cis-acting elements controlling nuclear export of RNA is critical, because they specify which RNA will be selected for transport. We have characterized the nuclear export motif of the adenoviral VA1 RNA, a small cytoplasmic RNA transcribed by RNA polymerase III. Using a large panel of VA1 mutants in both transfected COS cells and injected Xenopus oocytes, we showed that the terminal stem of VA1 is necessary and sufficient for its export. Surprisingly, we found that the nucleotide sequence within the terminal stem is not important. Rather, the salient features of this motif are its length and its relative position within the RNA. Such stems thus define a novel and degenerate cytoplasmic localization motif that we termed the minihelix. This motif is found in a variety of polymerase III transcripts, and cross-competition analysis in Xenopus oocytes revealed that export of one such RNA, like hY1 RNA, is specifically competed by VA1 or artificial minihelix. Taken together these results show that the minihelix defines a new cis-acting export element and that this motif could be exported via a novel and specific nuclear export pathway.

Animals↗
PubMed2001

Expression of LSLCL, a new C-type lectin, is closely restricted, in bone marrow, to immature neutrophils.

In vitro, LSLCL is expressed by numerous myeloid, promyelocytic, and T or B lymphoblastoid cell lines. In vivo, LSLCL is strongly expressed in bone marrow and only faintly in lymphoid organs. We show here that, in bone marrow, LSLCL is detected: (i) concentrated in the cytoplasm of immature neutrophils but not in myeloblasts nor in mature neutrophils, (ii) in extracellular bone marrow fluid. Besides, numerous cDNAs, similar to LSLCL (identity of 93-99%), are found in 'expressed sequence tags' databases from various origins, mostly fetal and undifferentiated tumour tissues. Since LSLCL and various closely related cDNAs are expressed at definite stages of cellular maturation processes, we hypothesize that this class of proteins could play an important role in the control of cellular differentiation.

Animals↗
PubMed2001

Theoretical perspectives on the relation between catastrophizing and pain.

The tendency to "catastrophize" during painful stimulation contributes to more intense pain experience and increased emotional distress. Catastrophizing has been broadly conceived as an exaggerated negative "mental set" brought to bear during painful experiences. Although findings have been consistent in showing a relation between catastrophizing and pain, research in this area has proceeded in the relative absence of a guiding theoretical framework. This article reviews the literature on the relation between catastrophizing and pain and examines the relative strengths and limitations of different theoretical models that could be advanced to account for the pattern of available findings. The article evaluates the explanatory power of a schema activation model, an appraisal model, an attention model, and a communal coping model of pain perception. It is suggested that catastrophizing might best be viewed from the perspective of hierarchical levels of analysis, where social factors and social goals may play a role in the development and maintenance of catastrophizing, whereas appraisal-related processes may point to the mechanisms that link catastrophizing to pain experience. Directions for future research are suggested.

Adaptation, Psychological↗
PubMed2001

A peptide derived from bee venom-secreted phospholipase A2 inhibits replication of T-cell tropic HIV-1 strains via interaction with the CXCR4 chemokine receptor.

We have previously shown that secreted phospholipases A2 (sPLA2) from bee and snake venoms have potent anti-human immunodeficiency virus (HIV) activity. These sPLA2s block HIV-1 entry into host cells through a mechanism linked to sPLA2 binding to cells. In this study, 12 synthetic peptides derived from bee venom sPLA2 (bvPLA2) have been tested for inhibition of HIV-1 infection. The p3bv peptide (amino acids 21 to 35 of bvPLA2) was found to inhibit the replication of T-lymphotropic (T-tropic) HIV-1 isolates (ID(50) = 2 microM) but was without effect on monocytotropic (M-tropic) HIV-1 isolates. p3bv was also found capable of preventing the cell-cell fusion process mediated by T-tropic HIV-1 envelope. Finally, p3bv can inhibit the binding of radiolabeled stromal cell-derived factor (SDF)-1alpha, the natural ligand of CXCR4, and the binding of 12G5, an anti-CXCR4 monoclonal antibody. Taken together, these results indicate that p3bv blocks the replication of T-tropic HIV-1 strains by interacting with CXCR4. Its mechanism of action however appears distinct from that of bvPLA2 because the latter inhibits replication of both T-tropic and M-tropic isolates and does not compete with SDF-1alpha and 12G5 binding to CXCR4.

Amino Acid Sequence↗
PubMed2001

Family pain history predicts child health status in children with chronic rheumatic disease.

OBJECTIVES: To examine the relationships of parental and family pain history on the pain experience of children with chronic rheumatic disease. The aims of the study were as follows: 1) to describe the pain history of parents and families of children with rheumatic disease, 2) to examine relationships between parental and family pain history and the pain report and physician-rated health status of children with chronic rheumatic disease, and 3) to determine whether child coping mediates the relationship between family pain history and the child's pain and physician-rated health status. METHOD: Parents of 100 children were recruited from a pediatric rheumatology clinic during routine visits. Parents completed questionnaires assessing parental pain history and family characteristics. Children in the study completed a series of questionnaires to assess pain and pain coping strategies, including the Coping Strategies Questionnaire and parts of the Pediatric Pain Questionnaire. A pediatric rheumatologist provided a global assessment of disease severity on a 100-mm visual analog scale as an index of child health status. RESULTS: A high number of parents of children seen in a pediatric rheumatology clinic described a personal pain history. More than 90% of parents reported having at least 1 chronic pain condition, with an equal proportion reporting an episode of pain in the past month. The most commonly reported pain conditions were lower back pain, shoulder/neck pain, and migraine headache pain. On average, this group of parents reported a history of 3.5 chronic pain conditions (standard deviation: 2.3) and reported having sought treatment for 1.7 (standard deviation: 2.3) of these conditions. Additionally, 93% of all parents reported extended family members experiencing at least 1 chronic pain condition. Correlational analyses indicated that parents reporting higher levels of current pain and higher mean levels of pain during the past month were more likely to have children reporting higher levels of current pain (r = 0.23 and r = 0.27). In addition, parents who sought more treatment for their own pain were more likely to have children reporting higher levels of pain (r = 0.22) and presenting with poorer health status (r = 0.22). Similarly, parents reporting higher levels of pain-related interference with activity were more likely to have children reporting higher levels of current pain (r = 0.23). Correlational analyses also indicated that children whose extended families reported a history of multiple pain conditions were more likely to report higher levels of current pain (r = 0.24) and more pain locations (r = 0.23). Finally, a series of mediational statistical models confirmed that child use of the pain coping strategy, catastrophizing, partially accounted for the relationship between several parent and family pain history variables and the child's own current pain ratings and physician global assessment. Specifically, child catastrophizing mediated the relationships between the total number of treated pain conditions and children's current pain ratings and physician global assessment. In addition, child catastrophizing was shown to mediate the relationship between parental mean level of pain in the past month and children's current pain rating and the relationship between total number of family pain conditions and children's current pain rating. Taken together, our results suggest that parental and familial pain experiences predict children's use of catastrophizing to cope with pain, which in turn predicts physician global assessment and children's current pain. CONCLUSIONS: The results from the present study indicate that many of the parents of children seen in a pediatric rheumatology clinic have a personal pain history and highlight the potential impact of parental pain history on children's pain experiences. Specifically, parents who were more likely to seek treatment for their own pain or more likely to report interference with recreational activities because of pain had children with higher pain ratings and poorer health status as measured by the physician global assessment. Additionally, a series of mediational models showed that child catastrophizing serves as a specific mechanism through which parental and familial pain history variables influence child ratings of current pain and physician ratings of health status. Future studies are needed to determine exactly how children living in families with painful conditions become more reliant on catastrophizing to cope with their pain. In addition, more research is needed to identify other potential mediators, such as positive ways parents may influence children's pain coping. There are several important clinical implications of our findings. First, our results suggest that by gathering information from parents about their own pain histories, health care providers may be able to identify children at risk for developing maladaptive pain coping strategies and higher levels of disease-related pain and disability. Second, our results indicate that intervention programs should focus specifically on reducing children's use of catastrophizing to cope with their pain. Perhaps most importantly, our results highlight the need to include parents in interventions aimed at reducing children's pain and improving children's abilities to cope with pain.

Adaptation, Psychological↗
PubMed2001

[An acute pseudo-cholecystitis].

In an emergency department, many patients were admitted with abdominal pain. The problem is to made the right diagnosis between an acute abdomen that must be manage by a medical approach and an acute abdomen with immediate surgical treatment. We present the case of a 44 year-old man admitted in our emergency department with clinical signs of acute cholecystitis. After a new interrogation and the inadequacy of the diagnostic procedures a lead intoxication treated by a medical approach was diagnosed.

Abdominal Pain↗
PubMed2000

The relationship of daily mood and stressful events to symptoms in juvenile rheumatic disease.

OBJECTIVES: The purpose of this study was 3-fold: 1) to assess the feasibility of a daily diary for use with children with juvenile rheumatic disease (JRD), 2) to describe daily variation in mood, stressful events, and symptoms in children with JRD, and 3) to examine the extent to which daily mood and daily stressful events predict daily symptoms in children with JRD. METHODS: Twelve children with JRD completed a daily booklet for 7 days. The daily booklet included measures of daily mood, daily stressful events, daily symptoms, and daily function. The children also completed a visual analog scale for pain and the Children's Depression Inventory. RESULTS: Subjects showed good compliance with scheduled completion and return of the daily diaries. Results indicated that children with JRD showed variability in daily mood, frequency of daily stressful events, and daily symptoms across days. Multilevel fixed effects models showed that more negative daily mood and more daily stressful events significantly predicted increased reports of fatigue, stiffness, and cutting back on daily activities. Negative daily mood also correlated with increases in daily reported pain. CONCLUSIONS: These results indicate that daily diary research is both feasible and potentially informative in children with JRD. Our data emphasize the need for further investigation into the role of daily mood and daily stressful events on disease course in JRD.

Activities of Daily Living↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗