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Biomedical subjects

J Bernard

Publications and source records attributed to J Bernard.

At least 19 recordsLinked to original sources
PubMed2006

Efficient transduction of monocyte- and CD34+-derived Langerhans cells with lentiviral vectors in the absence of phenotypic and functional maturation.

BACKGROUND: Gene delivery in dendritic cells (DC) has raised considerable interest to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific fashion. Among immature DC, Langerhans cells (LC) are attractive candidates for antigen delivery using lentiviral vectors (LV). METHODS: LC derived from monocytes (Mo-LC), or derived from CD34+ cells (CD34-LC) in the presence of cytokine cocktail, were transduced with LV expressing enhanced green fluorescent protein (E-GFP) under the control of the ubiquitous phosphoglycerate kinase (PGK) promoter at a multiplicity of infection of 18, at days 0 to 3 for Mo-LC, or at days 0 to 12 for CD34-LC. We assessed gene transfer levels from the percentage of E-GFP+ cells in the final cultures, and examined the morphology, immunophenotype, state of differentiation and function of transduced LC. RESULTS: Day 0 transduction of monocytes or CD34+ progenitors before cytokine pre-activation and LC differentiation resulted in stable gene expression in 7.8% of Mo-LC and 24% of CD34-LC. Monocyte-derived DC (Mo-DC) differentiated in serum-free medium were also efficiently transduced up to 13.2%. Interestingly, Mo-LC cells committed towards LC phenotype were permissive for transduction up to day 3. Transduction levels of CD34-LC peaked at day 6 to 44% and decreased thereafter. LV transduction did not perturb viability, phenotype and function of E-GFP-expressing LC. CONCLUSIONS: LC generated ex vivo can serve as vaccine vehicles in humans through efficient transduction by LV. These LC will be helpful to assess in vitro the immunogenicity of gene therapy vectors, from the characterization of their phenotypic and functional maturation.

Antigens, CD34↗
PubMed2006

Cell surface proteoglycan expression during maturation of human monocytes-derived dendritic cells and macrophages.

Cell surface proteoglycans play an important part in the functional and metabolic behaviour of leucocytes. We studied the expression of cell surface proteoglycans in human monocytes, in monocyte-derived immature and mature dendritic cells and in macrophages by metabolic labelling with [(35)S]-sulphate, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. Immature dendritic cells had the highest metabolic activity for the synthesis of cell surface proteoglycans. The major part of these proteoglycans was in phosphatidylinositol-anchored form and was released after treatment with phospholipase C. A minor part was released by trypsin. Digestion with chondroitinase ABC and mild HNO(2) treatment showed that cell surface proteoglycans had a higher proportion of chondroitin sulphate, both in the phospholipase C and trypsin fractions, suggesting that at least some glypicans contained chondroitin sulphate chains. RT-PCR detected the transcripts of glypicans 1, 3, 4 and 5 and all syndecans. Immature dendritic cells expressed a most complex spectrum of glypicans and syndecans, glypican-1 and syndecan-1 being expressed preferentially by this type of cells. Mature dendritic cells expressed glypican-3, which was not present in other lineages. These results suggest that different mononuclear cells synthesize cell surface proteoglycans actively with characteristic expression of different syndecans and glypicans genes, depending on the degree of cell differentiation and/or maturation.

Antigens, Surface↗
PubMed2005

Spinal injuries admitted to a specialist centre over a 5-year period: a study to evaluate delayed admission.

STUDY DESIGN: Retrospective study of 432 patients admitted to our institution with a spinal injury over a 5-year period. OBJECTIVES: To present epidemiological data relating to this spinal population, reporting specifically on delayed admission and length of hospitalisation. SETTING: Royal National Orthopaedic Hospital, Stanmore, UK. METHODS: A total of 432 traumatic spinal injuries admitted between March 1998 and March 2003 were analysed with respect to age, gender, mechanism of injury, level of bony injury, neurological level (complete, incomplete and intact), Injury Severity Score (ISS), date of injury, referral and admission independently and length of hospitalisation. The delays between injury and referral (>3 days) and between referral and admission (>7 days) were correlated to the length of hospitalisation. A detailed analysis of the cause of delay at both junctures was undertaken. RESULTS: There were 322 males (average age, 38.6 years) and 110 females (average age, 41.8 years) in our study. Classification of neurological severity disclosed 108 complete injuries, 115 incomplete and 209 intact. The average time between injury and referral was 5.5 days (range 0-94), and between referral and admission was 10.7 days (range 0-130). A total of 161 patients (37%) experienced a delay between injury and referral, of whom 59 (37%) were subsequently also delayed to admission. The principal reason for delay between injury and referral was the treatment of concurrent injuries. Even patients with complete injuries (15/43) experienced delayed referral. In all, 112 patients (26%) experienced a delay between referral and admission. Principal reasons included the provision of beds (Intensive care, acute and rehabilitation) and physiological stabilisation of other injuries particularly thoracic trauma. CONCLUSIONS: Provision of beds remains the most common preventable reason for delay between referral and admission and is associated with increased hospitalisation. Early liaison with a designated spinal injuries unit, particularly those with cord injury remains vitally important.

Adult↗
PubMed2005

Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy.

The aim of this study was to define standard values for fat mass distribution by dual-energy X-ray absorptiometry in human immunodeficiency virus (HIV)-negative men and to analyze factors associated with lipodystrophy in HIV-infected men. Total-body composition was analyzed in 241 HIV-negative men (controls) and 162 HIV-infected men. We created a fat mass ratio (FMR) as the ratio of the percentage of the trunk fat mass to the percentage of the lower limbs fat mass. We defined the FMR standard values as the mean value+/-standard deviation. We compared body mass index (BMI), fat mass percentage (%FM), lean mass (LM), bone mineral density (BMD), and FMR between the control group and HIV-infected men, by age range, according to prescription of treatment and presence of clinical lipodystrophy. The FMR standard value is equal to 1.3+/-0.2. The FMR was higher in treated HIV-infected men with or without clinical lipodystrophy. The FMR was similar for naïve HIV-infected men and controls. It was positively correlated with age, cumulative time on treatment, zidovudine, stavudine, or indinavir. BMD and fat mass were lower for treated and naïve HIV-infected men than for HIV-negative men. The FMR seems to be a valuable index for measuring fat mass distribution. We defined FMR standard values from the largest group of HIV-negative men to our knowledge. Applying FMR to HIV patients could help physicians to diagnose lipodystrophy earlier.

Absorptiometry, Photon↗
PubMed2004

Arthroscopic washout of the knee--a 5-year survival analysis.

Arthroscopy and washout of the knee is commonly performed for early osteoarthritis. Very little information exists regarding long-term prognosis, especially in terms of avoidance of further surgery. Using a prospectively gathered database, 100 consecutive patients having knee arthroscopy with a finding of OA between 1991 and 1993 were identified and their outcome at 5 years ascertained. Ninety-nine patients with 100 arthroscoped knees were identified. Fifty-eight had isolated medial compartment disease and six had isolated lateral compartment disease. In 36, both compartments were affected. Eighteen knees had further major surgery during follow up; 11 had total knee replacement, four had high tibial osteotomy and three had unicondylar knee arthroplasty. Those requiring surgery were significantly older (62 cf. 53 years, P=0.008). Meniscectomy was not an important risk factor (chi2, P=0.67). The rate of knee survival without operation at 5 years was much lower in those aged over 60 years than in those younger (68% cf. 89%). (chi2, P=0.02). Only 18% of patients progress to major knee surgery within 5 years of arthroscopic washout for osteoarthritis. Age greater than 60 years worsens the prognosis considerably.

Arthroscopy↗
PubMed2004

The immunosuppressive effect of vincristine on allostimulatory potential of human dendritic cells interferes with their function and survival.

Mature dendritic cells (mDC) are professional and potent antigen presenting cells required for initiation of primary immune responses. In the present study, we have investigated the effect of vincristine on the T cell allostimulatory potential of human monocyte-derived mDC in allogeneic mixed lymphocyte reaction. Using T lymphocytes as responding cells and mDC as stimulating cells, our data indicate that incubation of DC with vincristine decreased the accessory potency dose dependently and resulted in a subsequent inhibition of T cell proliferative responses. Treatment of mDC with vincristine also led to the alteration of their capacity to produce IL-12 but enhanced their production of IL-10. Using flow cytometry, we demonstrated that vincristine had no effect on mDC phenotype (CD83, CD40, CD86, CD58, CD54) but promoted apoptotic cell death of these cells as revealed by PI and annexin-V. These findings suggest that DC may be potential targets of cytotoxic drugs and point out the possible impairment of the immunocompetence of these cells following chemotherapy.

Antigens, CD↗
PubMed2003

Dendritic cell KLH loading requirements for efficient CD4+ T-cell priming and help to peptide-specific cytotoxic T-cell response, in view of potential use in cancer vaccines.

This study focuses on a Keyhole Limpet Hemocyanin (KLH) adjuvant strategy to augment efficacy of dendritic cell-based vaccines that use class I-restricted peptides. Requirements for loading dendritic cells (DC) with KLH were first determined in order to optimally prime CD4(+) T cells. These KLH-loaded cells were pulsed with antigenic peptide and cultured with T cells to induce a cytotoxic T lymphocyte (CTL) response against the peptide. Such a concomitant presentation of KLH and peptide by the same DC strongly augmented the peptide-specific CTL response, as compared to the response induced by DC pulsed with the peptide alone. This adjuvant effect was more pronounced for poorly immunogenic antigens. The use of optimised peptide and KLH-loaded DC may improve the efficacy of therapeutic anti-tumour peptide vaccination.

Adjuvants, Immunologic↗
PubMed2003

Ethnicity as a factor in pizza delivery crashes.

A subjective assessment of patients admitted acutely to the orthopedic directorate revealed that there had been--over a short period of time--a small series of patients who had sustained fractures during the course of their employment as pizza delivery moped drivers. Consequently an observational study was performed in our district general hospital in order to investigate this further, and establish the demographic domain of the patients involved and the cost of their injuries. Our hospital has a patient catchment area of 350,000 and an emergency department that treats 95,000 patients annually. The patients in this series were described in terms of their injuries, ethnicity, and cost of injury treatment. The main findings were that pizza delivery personnel admitted acutely were male Afghans, with poor English language skills, who sustained significant fractures in moped accidents that were expensive to treat.

Accidents, Occupational↗
PubMed2002

Very fast hollow-atom decay processes in Xe30+-C60 collisions.

In Xe30+-C60 collisions at low velocity (0.2 a.u.<v<0.4 a.u.), very fast electron ejection is observed not only for frontal collisions but also for near C60 cage collisions. In frontal collisions, the exit-charge distributions obtained with three projectile velocities are reproduced using a multistep exponential decay model. A mean Auger rate of about 0.4 a.u. is estimated for the decay of hollow atoms during the very short interaction time (<3 fs).

Journal Article↗
PubMed2002

Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages.

We studied the in vitro effects of butyric acid on differentiation, maturation and function of dendritic cells (DC) and macrophages (M(Phi)) generated from human monocytes. A non-toxic dose of butyrate was shown to alter the phenotypic differentiation process of DC as assessed by a persistence of CD14, and a decreased CD54, CD86 and HLA class II expression. The more immature differentiation stage of treated cells was confirmed further by their increased phagocytic capability, their altered capacity to produce IL-10 and IL-12, and their weak allostimulatory abilities. Butyrate also altered DC terminal maturation, regardless of the maturation inducer, as demonstrated by a strong down-regulation of CD83, a decreased expression of CD40, CD86 and HLA class II. Similarly, butyrate altered M(Phi) differentiation, down-regulating the expression of the restricted membrane antigens and reducing the phagocytic capacity of treated cells. To investigate further the mechanism by which butyrate hampers the monocyte dual differentiation pathway, we studied the effects of 1,25(OH)2D3 alone or in combination with butyrate on the phenotypic features of DC. Unlike 1,25(OH)2D3, butyrate inhibited DC -differentiation without redirecting it towards M(Phi). Combined treatment gave rise to a new cell subset (CD14(high), CD86 and HLA-DR(low)) phenotypically distinct from monocytes. These results reveal an alternative mechanism of inhibition of DC and M(Phi) differentiation. Altogether, our data demonstrate a novel immune suppression property of butyrate that may modulate both inflammatory and immune responses and support further the interest for butyrate and its derivatives as new immunotherapeutic agents.

Antigen Presentation↗
PubMed2002

[Creation of an educational CD-ROM using a PACS].

Presentation of MIRIAM 2: We describe the materials used for the creation of and the content of a CD-ROM entitled '77 neuroradiological case reports'. We mention the gathering of clinical and imaging data, exclusively provided by a PACS. Our work demonstrates that a CD-ROM is an appropriate interactive medium for radiological teaching. Its creation can be simplified thanks to a PACS, but it nonetheless remains work intensive.

Brain Diseases↗
PubMed2002

[Value of MRI to evaluate extra-abdominal desmoid fibromatosis].

PURPOSE: To describe the MR appearance of extra-abdominal desmoid fibromatosis, especially using sequences such as MR angiography, STIR and FAT SAT. Materials and methods. We reviewed retrospectively the MRI studies of 8 patients (4 men and 4 women) with histologically proved desmoid fibromatosis. In five patients the lesion corresponded to recurrent disease. Eleven MRI examinations were available (Siemens, Vision, 1.5T) including the following sequences: pre- and postcontrast T1 weighted (11 cases), STIR (9 cases), and MRA (3 cases). All lesions were imaged in at least two orthogonal planes. CT was available for 5 patients. RESULTS: The lesions were localized to the girdles in 8 cases and to the upper extremity in 3 cases. Most lesions (10/11) were isointense to muscle on noncontrast T1W images and showed intense enhancement on postcontrast T1W images. All lesions (9/9) were hyperintense on STIR images. CONCLUSION: A STIR sequence is useful as a first sequence to identify smaller lesions (usually recurrences) and to better adapt the FOV of following sequences, especially before administration of intravenous contrast. MR angiography may be valuable for surgical planning.

Adult↗
PubMed2001

Bone mineral density of 704 amateur sportsmen involved in different physical activities.

The aim of the study was to analyze the relation between sports and bone mass. Seven hundred and four men with no history of chronic disease were questioned on their adolescent and adult sporting activities. Their total body (TB) and regional (head, spine, arms and legs) bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry. BMD measurements and ratios of regional BMD to TB BMD were compared using a multiple regression analysis. Probands (mean age 30 years) were engaged in 14 sports activities: rugby, soccer, other team sports, endurance running, fighting sports, bodybuilding, multiple weightbearing activities, swimming, swimming with flippers, biking, rowing, climbing, triathlon and multiple mixed activities. They stated that they were practising a physical activity at the amateur level: 7.1 h/week between the ages of 11 and 18 years and 9 h/week between age 18 years and the day of the interview (no significant difference between physical activities). Rowers and swimmers had low TB BMD (1.22 and 1.17 g/cm2) and low leg BMD (1.37 and 1.31 g/cm2). Participants in rugby, soccer, other team sports and fighting sports had a high TB BMD (1.27-1.35 g/cm2) and high leg BMD (1.41-1.5 g/cm2). For head BMD, there was no stastistical difference among the different groups. Constructed ratios pointed out the site-specific adaptation of the skeleton: soccer player and runners had a higher leg ratio; bodybuilders, fighters, climbers and swimmers had a higher arm ratio; rugby players had a higher spine ratio. Head ratio was higher in non-weightbearing sports (rowing, swimming) than in weightbearing sports (rugby, team sports, soccer, fighting sports and bodybuilding). Thus the BMD and ratio differences among the 14 disciplines seem to be site-specific and related to the supposedly high and unusual strains created at certain sites during sport training by muscle stress and gravitational forces. Head ratio is closely related to the type of practice; its value could predict whether sport participants have developed the maximal peak bone mass they could achieve.

Absorptiometry, Photon↗
PubMed2001

Silicone punctal plug extrusion resulting from spontaneous dissection of canalicular mucosa: A clinical and histopathologic report.

PURPOSE: To report on an uncommon, previously unidentified, progressive silicone punctal plug extrusion. DESIGN: Small, retrospective case series. PARTICIPANTS: Five cases of punctal plug extrusion were identified among a series of 424 consecutive implantations. Histopathologic analysis was obtained in one case. One additional referred case was included in this report. RESULTS: The plugs were completely extruded from the punctal lumen 6 to 14 months after insertion after an otherwise uncomplicated postoperative course. All plugs were retained at the punctal margin by an encircling band of vascularized mucosal tissue originating from the canalicular lumen. The band consisted of connective tissue of canalicular mucosal origin, attached just below the junction of the punctal and canalicular epithelium. Mild mononuclear infiltration was present in the connective tissue component of the punctal region. There was no cytologic or architectural evidence of abnormal epithelium or connective tissue or of pyogenic granuloma. CONCLUSIONS: These observations suggest that progressive lacrimal punctal plug extrusion may relate to mucosal dissection by the plug edges. We speculate that mechanical stress induced by eyelid closure on an improperly sized or placed implant may result in plug tilt. Subsequent epithelial hyperplasia further enhances the tilt, and the sharper edge of the conical bulb promotes separation of the canalicular mucosa from its distal luminal aspect. At the completion of the extrusion, the mucosal surface is separated from its connective tissue base, at a proximal subpunctal level, causing formation of an encircling tissue band.

Adult↗
PubMed2001

Effects of clodronate on vertebral fracture risk in osteoporosis: a 1-year interim analysis.

The aim of this study was to determine whether clodronate reduced the incidence of vertebral fractures in patients with osteoporosis. We report here the interim analysis after 1 year of a 3-year double-blind placebo-controlled study. The objectives of the interim analysis were to determine whether there was a trend in fracture frequency and to examine the effects of clodronate on bone mineral density (BMD). Patients with densitometrically proven osteoporosis (T-score <-2.5 and <-3 for women and men, respectively) or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind, controlled study. Patients were randomized to three strata, namely women with postmenopausal osteoporosis (stratum I, n = 483), women with secondary osteoporosis (II, n = 110), and men with osteoporosis of any causation (III, n = 84). They received either clodronate 800 mg daily by mouth or an identical placebo, and all patients received a calcium supplement of 500 mg daily. BMD was measured at six monthly intervals, and lateral spine radiographs for vertebral morphometry were obtained at baseline and 1 year. Treatment with clodronate was associated with a significant increase in BMD at the spine of 3.2 +/- 0.3% (p < 0.0001 vs. baseline) compared with a nonsignificant change of 0.5 +/- 0.3% in the placebo group (p < 0.0001 between treatments). At the hip, clodronate was associated with a significant increase in total hip BMD of 1.3 +/- 0.3% (p = 0.018 vs. baseline) compared with a small decrease of 0.4 +/- 0.3% in the placebo group (p = 0.027 for the difference between treatment groups). The mean changes at the spine and hip were similar in all three strata. Incident vertebral fractures were observed in 27 patients at 1 year in the placebo group (9.0%) and in 14 patients receiving clodronate (4.9%) (relative risk 0.54; 95% CI 0.29-1.02; p = 0.07). A trend was observed in all treatment strata. Treatment was well tolerated, with no significant adverse events attributable to clodronate treatment. We conclude that clodronate 800 mg daily is effective in preventing bone loss, and at 1 year, there is a trend consistent with antifracture efficacy in patients with established osteoporosis regardless of causation.

Bone Density↗