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Biomedical subjects

C Boyer

Publications and source records attributed to C Boyer.

At least 37 records · Page 2Linked to original sources

HONselect: multilingual assistant search engine operated by a concept-based interface system to decentralized heterogeneous sources.

Any new user to the Internet will think that to retrieve the relevant document is an easy task especially with the wealth of sources available on this medium, but this is not the case. Even experienced users have difficulty formulating the right query for making the most of a search tool in order to efficiently obtain an accurate result. The goal of this work is to reduce the time and the energy necessary in searching and locating medical and health information. To reach this goal we have developed HONselect [1]. The aim of HONselect is not only to improve efficiency in retrieving documents but to respond to an increased need for obtaining a selection of relevant and accurate documents from a breadth of various knowledge databases including scientific bibliographical references, clinical trials, daily news, multimedia illustrations, conferences, forum, Web sites, clinical cases, and others. The authors based their approach on the knowledge representation using the National Library of Medicine's Medical Subject Headings (NLM, MeSH) vocabulary and classification [2,3]. The innovation is to propose a multilingual "one-stop searching" (one Web interface to databases currently in English, French and German) with full navigational and connectivity capabilities. The user may choose from a given selection of related terms the one that best suit his search, navigate in the term's hierarchical tree, and access directly to a selection of documents from high quality knowledge suppliers such as the MEDLINE database, the NLM's ClinicalTrials.gov server, the NewsPage's daily news, the HON's media gallery, conference listings and MedHunt's Web sites [4, 5, 6, 7, 8, 9]. HONselect, developed by HON, a non-profit organisation [10], is a free online available multilingual tool based on the MeSH thesaurus to index, select, retrieve and display accurate, up to date, high-level and quality documents.

Databases, Bibliographic↗

[Leiomyosarcoma and stromal tumor of the pancreas].

A tumor of the head of pancreas was an incidental finding on US of two patients aged 52 and 61 years presenting with abdominal pain. The tumor was studied by computed tomography, MRI and endoscopic ultrasonography. Surgical biopsy of a liver lesion was performed in one case and partial duodenopancreatectomy was performed in the other case. Histological evaluation, including immunohistochemistry, showed leiomyosarcoma and stromal tumor respectively. Whatever the site of origin, most mesenchymal pancreatic tumors are hypervascular, heterogeneous and have a necrotic center.

Female↗

Recent HIV testing among general hospital inpatients with schizophrenia: findings from four New York City sites.

BACKGROUND: While widely acknowledged to be an important clinical and public health issue, HIV assessment, counseling, and testing for the seriously mentally ill has not been well studied. OBJECTIVE: To determine what proportion and which inpatients with schizophrenia have been recently tested for HIV. METHOD: A sample of 300 inpatients with schizophrenia were recruited from four general hospitals in New York City over a one year period. After confirmation of diagnosis with a structured interview, and elicitation of sociodemographic and drug use information, medical record review identified recent HIV testing. Bivariate and multivariate analyses were used to identify subgroups more likely to be tested. FINDINGS: Recent HIV testing had been performed for 17% of the sample and was concentrated among those with higher documented risks. The majority of patients remain untested even in groups with direct risks, such as injection drug use, and indirect risks, such as frequent cocaine use in last year. Some evidence was found that white patients at risk may be less likely to be tested than Hispanic or African American patients. CONCLUSIONS: Aggressive efforts are needed to improve knowledge of HIV status among acutely ill patients with schizophrenia.

Adult↗

The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection.

Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes and peripheral T cells. Taken together the results suggest that the lack of PKC epsilon in DP thymocytes could lead to the absence of NF-kappa B activity after antigenic stimulation contributing to negative selection. Cell Death and Differentiation (2000) 7, 1253 - 1262.

Animals↗

Patients with schizophrenia at risk for excessive antipsychotic dosing.

BACKGROUND: Patient Outcomes Research Team treatment recommendations were used to investigate the relationship between patient characteristics and higher-than-recommended dosages (> 1000 chlorpromazine equivalents [CPZe]) at discharge. METHOD: Inpatients who met the DSM-IV criteria for schizophrenia or schizoaffective disorder were recruited from 4 general hospitals. For those patients (N = 293) prescribed antipsychotics at discharge, chi-square tests and multiple regression analyses were used to assess the relationship between demographics, admission characteristics, comorbid diagnoses, and antipsychotic dosages. The relationship between clinical symptoms and antipsychotic dosage at discharge was also examined. RESULTS: Antipsychotic dosages conformed to treatment guidelines for approximately 65% of patients; 21% received doses in excess of recommended levels. African American patients and those with a history of psychiatric hospitalization were more likely to be prescribed discharge antipsychotic doses greater than 1000 CPZe. Hospital differences in antipsychotic management were also observed. Regression analyses indicated that higher-than-recommended dosages found among African American patients could not be explained by differences in symptom levels at discharge. Patients with more thought disorder were also more likely to be prescribed antipsychotic dosages in excess of the recommended range. Compared with oral administration, depot administration increased the risk of excess dosage by a factor of 30. Controlling for method of administration reduced the impact of race to nonsignificance. CONCLUSION: These results replicate earlier findings that minority individuals are more likely to be prescribed dosages in excess of the recommended range and suggest that this pattern is due to higher use of depot injection in African American patients. Further research should examine how patient characteristics and institutional factors influence medication use.

Administration, Oral↗

User acceptance by individuals of health telematics from distributed EPRs associated with knowledge couplers.

The patient in a hospital bed is also a private individual that might access his or her own Electronic Patient Record (EPR) in association with additional tools that are able to show critical up-to-date knowledge about diagnoses, clinical investigations or treatments. The distributed EPRs are shown here in full production with the DOMED application of DIOGENE 2. Besides, in order to facilitate an easier understanding of the EPRs by the patient, the HON Web Site services are at his or her disposal in this respect at the same terminal.

Artificial Intelligence↗

Effects of pediatric head trauma for children, parents, and families.

Severe pediatric head injury has negative consequences for children of all ages. Even mild and moderate head injury results in residual impairment for school-age children and adolescents. Data are needed on the effects of these less severe insults, especially for preschoolers. Although research on the impact of the child's head injury on the parent-child relationship and family functioning is limited, the experience is likely to be very stressful for the parent and the family. Indeed, family integrity may be at risk. Research is needed that examines the effects of a child's head injury for the parent and the family over time and identifies factors related to these outcomes.

Adult↗

Rat decidual prolactin. Identification, molecular cloning, and characterization.

Establishment and maintenance of pregnancy require the activity of a highly specialized maternal tissue, the decidua. It is well established that the human decidua synthesizes and releases prolactin. However, in the rat, no study has been able to demonstrate the production of prolactin by the decidua. In this report, we established for the first time using Northern blot analysis and reverse transcription-polymerase chain reaction, Western blot analysis, immunocytochemistry, and enzyme-linked immunosorbent assay, that a defined cell population located in the rat antimesometrial decidua expresses prolactin mRNA, as well as synthesizes and secretes this hormone. By reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends, we cloned a full-length cDNA for rat decidua prolactin, whose sequence was identical to that of pituitary prolactin. Our results also showed that pituitary prolactin appeared to down-regulate decidual prolactin levels. Under these circumstances, inhibition of pituitary prolactin secretion led to a rise in both decidual prolactin mRNA and protein expression. Moreover, addition of exogenous prolactin to primary decidual cells in culture also caused a marked decrease in decidual prolactin mRNA expression. Finally, treatment of primary decidual cells with steroid hormones or 8-bromo-cAMP revealed a differential regulation of decidual prolactin expression from that of pituitary suggesting a tissue-specific regulation of prolactin gene expression, possibly through the use of an alternative promoter in rat decidua.

Amino Acid Sequence↗

Selection of phenotypically distinct NK1.1+ T cells upon antigen expression in the thymus or in the liver.

Unlike the main TCR alphabeta T cell lineage in which deletion occurs at the CD4+ CD8+ double-positive (DP) stage upon TCR engagement by antigen in the thymus, some T cells appear to require such engagement for their selection, either in the thymus or extrathymically. We used a transgenic TCR (tgTCR) model which, as we previously showed, led to selection upon expression of the corresponding antigen H-2Kb (Kb) in the thymus, of tgTCR/CD3(lo) CD4- CD8- double-negative (DN) thymocytes that expressed the NK1.1 marker (NK T cells) (Curnow, S. J., et al., Immunity 1995. 3: 427). We now report that antigen expression on medullary epithelial cells of the thymus failed to select the NK T cells, whereas its expression on thymocytes did, although tgTCR DP thymocyte development was affected under both conditions. Antigen expression on hepatocytes (Alb-Kb mice) did not perturb tgTCR DP thymocyte development. No enrichment in tgTCR NK T cells was detected in the periphery, except for the liver of the Alb-Kb/tgTCR mice. When reconstitution of thymectomized and irradiated H-2k hosts expressing or not Kb was performed with bone marrow from tgTCR H-2k mice, an enrichment in tgTCR+ NK T cells was found in the liver, but not in the spleen, of the hosts which expressed Kb, either selectively on hepatocytes or ubiquitously. Surprisingly, the majority of the hepatic tgTCR+ NK T cells also expressed the CD8 alpha/beta heterodimer. These results indicate that thymus-independent NK T cells with unique phenotypic characteristics can be selected upon antigen encounter in the liver.

Animals↗

Crippling of CD3-zeta ITAMs does not impair T cell receptor signaling.

We evaluated the importance of CD3-zeta ITAMs in T cell responses by breeding the P14 transgenic TCR into mice in which CD3-zeta chains lacking all or part of their ITAMs were genetically substituted for wild-type CD3-zeta chains. In contrast to the H-Y TCR, the P14 TCR permitted the development of peripheral CD8+ T cells harboring signaling-defective CD3-zeta subunits. The absence of functional CD3-zeta ITAMs did not reduce the spectrum of activation events and effector functions that constitute the normal attributes of mature CD8+ T cells. The only detectable differences were quantitative and noted only when T cells were challenged with suboptimal peptide concentrations. Therefore, the ITAMs present in the CD3-gammadeltaepsilon module are sufficient for qualitatively normal TCR signaling and those present in CD3-zeta have no exclusive role during T cell activation.

Animals↗

K+-dependence of Na+-Ca2+ exchange in type I vestibular sensory cells of guinea-pig.

The properties of the vestibular Na+-Ca2+ exchanger in mammalian type I vestibular sensory cells were studied using fura-2 fluorescence and immunocytochemical techniques. In the absence of external Na+, the activation of Na+-Ca2+ exchange in reverse mode required the presence of external K+ (K+o) and depended on K+o concentration. Alkali cations Rb+ and NH4+ but not Li+ or Cs+ substituted for K+o to activate the exchange. For pressure applications of 10 mm K+, the contribution of voltage-sensitive calcium channels to the increase in [Ca2+]i was < 15%. The dependence of the exchange on [K+]o was also recorded when the membrane potential was clamped using carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) and monensin ionophores. In these conditions, where there was no intracellular Na+, the increase in [Ca2+]i was completely blocked. These physiological results suggest that in reverse mode, Ca2+ entry is driven by both an outward transport of Na+ and an inward transport of K+. The dependence of the vestibular Na+-Ca2+ exchanger on K+ is more reminiscent of the properties of the retinal type Na+-Ca2+ exchanger than those of the more widely distributed cardiac type exchanger. Moreover, the immunocytochemical localization of both types of exchange proteins in the vestibular sensory epithelium confirmed the presence in the vestibular sensory cells of a Na+-Ca2+ exchanger which is recognized by an antibody raised against retinal type and not by an antibody raised against the cardiac type.

Alkalies↗

Antigen-induced TCR-CD3 down-modulation does not require CD3delta or CD3gamma cytoplasmic domains, necessary in response to anti-CD3 antibody.

We studied cytotoxic T lymphocyte (CTL) clones expressing cytoplasmic domain-deleted CD3delta and CD3gamma chains. These cells retained efficient antigen-specific cytolysis. Because the cytoplasmic domains of native CD3delta and CD3gamma chains contain a dileucine-based and a tyrosine-based motif thought to be important for receptor endocytosis, we compared TCR-CD3 down-modulation on the CTL clones expressing or not these domains. We found that antigen-induced TCR-CD3 down-modulation was not dependent on either the CD3delta or CD3gamma cytoplasmic domains. This contrasts with phorbol ester- and anti-CD3 mAb (soluble or plastic-coated)-induced TCR-CD3 down-modulation, that are respectively dependent on CD3gamma and on either CD3delta or CD3gamma cytoplasmic domains, suggesting that differences may exist between the mechanisms of TCR-CD3 down-modulation in response to the three stimuli. TCR-CD3 down-modulation in response to antigen was demonstrated by confocal microscopy to be associated with TCRbeta chain internalization, whether CD3delta and CD3gamma were native or truncated. Inhibition by the protein tyrosine kinase inhibitor PP1 of TCR-CD3 down-modulation in response to antigen was also similar whether CD3delta and CD3gamma cytoplasmic domains were present or not. These properties of receptor down-modulation are discussed with respect to the requirements for TCR engagement on antigen-presenting cells.

Animals↗

[Internet for physicians: a tool for today and tomorrow ].

The Internet is becoming more and more part of our habits regarding documentation and communication, thus limiting the frontiers to only that of the language. As in many other fields, the Internet is also present in the medical domain. The Internet is accessible to all, providing a technology which is simple and ergonomic and furthermore less costly. A growing number of individuals are indeed offering information, and the multiplication and diversification of documentary thus resulting renders the quality often questionable and the search for information difficult. This article firstly presents the Internet services with examples in the medical domain and more particularly in paediatrics. It then identifies the problems related to the Internet and further details three tools useful to find medical information and to surf on the Internet: Medline, a bibliographical reference search tool (from the National Library of Medicine-NLM); Medhunt, a search tool of the Health on the Net Foundation specialised in the health domain; and the HONcode, a code of ethics developed to homogenize medical information on the Internet.

Computer User Training↗

[Treatment of complicated renal colic in patients treated with indinavir: value of double J stents].

OBJECTIVE: Evaluation of the treatment of complicated ureteric stones in patients treated with indinavir. PATIENTS AND METHODS: From March 1997 to May 1998, 10 patients (7 males, 3 females, aged 30 to 56 years), treated by triple combination therapy for HIV infection, were drained for stones attributed to indinavir (CRIXIVAN), which had become obstructive and complicated. The duration of treatment with indinavir ranged from 14 days to 2 years. No patient had a history of urological disease. One patient presented with bilateral stones. All patients presented complicated clinical features: fever in 3 cases; severe pain in 8 cases, with delayed excretion more than 4 hours on IVU in 6 cases. All stones were radiolucent except for one slightly radioopaque stone. The stone was situated in the lumbar ureter in 3 cases, iliac ureter in 1 case and pelvic ureter in 8 cases. RESULTS: In 10 out of 11 cases, a double J stent was inserted, preceded by drainage by simple ureteric catheter (infected urine) in 1 case and by percutaneous nephrostomy (PCN) with antegrade insertion of the stent (failure of the retrograde route) in 1 case. No complementary stone fragmentation or extraction treatment was necessary after this procedure. Stents were left in place for 3 to 7 weeks. In one case, a stone of the lumbar ureter required PCN followed by extracorporeal lithotripsy. CONCLUSION: In the case of complications requiring a urological procedure, insertion of a double J stent allows curative treatment of very friable indinavir stones, which are fragmented by passage of the stent.

Adult↗

[How to plan the treatment of prostatic adenoma today?].

Surgical treatment, mainly transurethral resection of the prostate, still remains the reference treatment for benign prostatic hyperplasia (BPH). Two studies conducted in the Urology Department of the Pitié-Salpêtrière Hospital have tried to define certain characteristics of this surgery. The first study tried to evaluate the long-term outcome of patients operated for benign prostatic hyperplasia. Analysis of 881 replies to a questionnaire sent to 3,147 patients operated for BPH (between 1976 and 1989) assessed functional status (by Madsen's symptom score), quality of life (by Fowler's method), and sex life (by two specific questions), with a follow-up ranging from 5 to 14 years. At this follow-up, 90% of patients declared to be satisfied with their voiding status, 95% considered their quality of life to be excellent and about 50% had maintained a sex life. The second study was designed to evaluate the morbidity of this treatment in elderly patients. A group of 33 operated patients over the age of 80 was compared to a control group composed of 66 patients between the ages of 60 and 70 years, treated in a similar way, in the same centre and in the same year. Morbidity was higher in the first group, but age itself did not appear to constitute a poor prognostic factor for surgery; it only intervenes by allowing certain complications of benign prostatic hyperplasia (acute retention) to create emergency situations complicating the perioperative period. Following demonstration of the short-term and long-term efficacy of this conventional surgery, many new technologies were subsequently developed in order to reduce perioperative discomfort, anaesthetic requirements, duration of catheterization and hospital stay. Some of them constitute a new approach to endoscopic surgery, such as prostatic tissue vaporization techniques (electrovaporization, laser contact vaporization), which have a comparable efficacy to that of TURP, while reducing bleeding, catheterization time and hospital stay. However, the duration of postoperative irritative symptoms is much longer. Other techniques use a thermal effect to obtain coagulation necrosis of prostatic tissue, using various energy sources: microwaves (thermotherapy), laser (interstitial laser), radiofrequency waves (TUNA). These techniques are perfectly adapted to outpatient surgery with local or regional anaesthesia. They do not interfere with continence, sexual function, but may be followed by high dysuria or retention rates, with a variable cathererization time, sometimes several weeks. Finally, urethroprostatic stents are easy to insert, provide a solution in critical situations and have replaced old indwelling catheters. The current choice of treatment therefore comprises several approaches: more effective, but still purely symptomatic medical treatment, safe conventional surgery providing excellent long-term results, but generating a certain perioperative discomfort and a certain morbidity, or, on the contrary "minimally invasive" techniques, greatly simplifying the therapeutic procedure, but whose morbidity has not yet been determined and whose results are still uncertain.

Adenoma↗

The outcome of heregulin-induced activation of ovarian cancer cells depends on the relative levels of HER-2 and HER-3 expression.

Members of the epidermal growth factor receptor family of tyrosine kinases, including epidermal growth factor receptor, c-erbB-2 (HER-2), c-erbB-3 (HER-3), and c-erbB-4 (HER-4), can be coexpressed at different levels in nonhematopoietic tissues. Amplification and overexpression of HER-2 is found in approximately one-third of cancers that arise in the breast and ovary. In our previous studies, heregulin (HRG) and anti-HER-2 antibodies inhibited proliferation, increased invasiveness, and enhanced tyrosine autophosphorylation of SKBr3 breast cancer cells that overexpressed HER-2. In the present report, the effects of HRG and anti-HER-2 antibody have been compared in six ovarian cancer cell lines. HRG inhibited anchorage-independent growth of SKOv3 cells that overexpressed HER-2 (10(5) receptors/cell) but stimulated the growth of OVCA420, OVCA429, OVCA432, OVCA433, and OVCAR-3 cells that expressed lower levels of the receptor (10(4) receptors/cell). Thus, cell lines with a high level of HER-2 relative to HER-3 or HER-4 were growth inhibited, whereas cell lines with lower levels of HER-2 were growth stimulated by HRG. Stimulation or inhibition of clonogenic growth did not correlate with endogenous expression of HRG or with the impact of exogenous HRG on phosphorylation of HER-2, HER-3, or HER-4. Anti-HER-2 antibodies inhibited the growth of SKOv3 cells but failed to affect the growth of the other cell lines. In OVCAR-3 cells that had been transfected with HER-2 cDNA to increase expression to 10(5) receptors/cell, HRG inhibited rather than stimulated growth. Conversely, when HER-2 expression by SKOv3 cells was downregulated by transfection of the viral E1A gene, HRG stimulated rather than inhibited growth. To evaluate the relative importance of HER-3 and HER-4, NIH 3T3 cells were cotransfected with HER-2 and HER-3 or with HER-2 and HER-4. HRG inhibited the growth of cells with a high ratio of HER-2:HER-3, whereas HRG stimulated the growth of cells with low levels of the two receptors. In cells that express only HER-2 and HER-4, HRG stimulated the growth of cells that expressed HER-4 independent of HER-2 levels. Anti-HER-2 antibodies inhibited the growth of transfectants with high levels of HER-2 expression independent of HER-3 or HER-4 expression. In ovarian cancer cells that express all three receptors, the relative levels of HER-2 and HER-3 appear to determine the response to HRG. Taken together, these studies support the concept that the level of HER-2 expression can modulate response to HRG, determining whether the response is stimulatory or inhibitory. In contrast, agonistic antibodies that bind to HER-2 alone inhibit anchorage-independent growth but fail to mimic HRG's ability to stimulate growth of cells with low HER-2: HER-3 ratios.

Antibodies, Monoclonal↗

Fluorescent in situ hybridization on flow-sorted cells as a tool for evaluating minimal residual disease or chimerism after allogenic bone marrow transplantation.

We studied the feasibility and the sensitivity of fluorescent in situ hybridization (FISH) using leukemic or host/donor-specific probes on flow-sorted cells to assess minimal residual disease (MRD) or chimerism in transplanted patients in complete remission. We first performed experimental models of MRD and chimerism by mixing HL60 cells and normal lymphocytes in different proportions. Over 80% HL60 cells were obtained from mixtures of 5% HL60 cells in peripheral blood mononuclear cells (PBMC). We then evaluated MRD and mixed chimerism in a chronic myelogenous leukemia patient in relapse after allogeneic sex-mismatched bone marrow transplantation (BMT), who had received a donor lymphocyte infusion (DLI). Three months after DLI, mixed chimerism was observed in each bone marrow (BM)-sorted lineage (CD13+, CD14+, CD20+, and CD3+), with the highest level of recipient cells in the granulocytic lineage (CD13+). Five months after DLI, host cells were at a low level but remained detectable in the granulocytic lineage. In the same sample, the bcr-abl gene was detected in the granulocytic lineage and not in the lymphocytes. We also studied chimerism in an aplastic anemia sex-mismatched transplanted female patient. We determined the proportion of recipient total lymphocytes, CD4+ and CD8+ lymphocytes, and CD14+ monocytes under cyclosporin A therapy on five peripheral blood samples and one BM sample over 5 months. Results showed a regular decrease in recipient total lymphocytes (26.6% to 10.6%) and monocytes (20.7% to 8%). CD8(+)-recipient cells decreased rapidly, while CD4+ remained stable (17%). This work demonstrates the feasibility of FISH after cell sorting, combining the sensitivities of both flow cytometry and FISH and the specificities of both immunophenotyping and genotype analysis.

Anemia, Aplastic↗