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Biomedical subjects

B Durand

Publications and source records attributed to B Durand.

At least 37 records · Page 2Linked to original sources

Use of the malleus handle as a landmark for localizing the round window membrane.

Localization of the round window membrane is desirable in order to allow a more direct application of medication to the inner ear. A new procedure has been developed to deliver direct, near-continuous inner ear perfusion to the round window with the Silverstein MicroWick. In this office procedure, the wick is inserted through a tympanostomy tube into the round window niche. Accurate localization of the round window is a necessary component of this procedure. In an effort to ascertain the precise location of the round window, we examined 25 cadaveric human temporal bones and measured the distance from the umbo to the round window in each sample. We found that the round window was an average of 3.44 mm (+/- 0.68) from the umbo and was situated at an average angle of 113.2 degrees (+/- 9.8) from the long process of the malleus. Our simple and reliable determination of the relationship between the malleus handle and the round window niche allows for the accurate placement of the Silverstein MicroWick and other devices.

Cadaver↗

Living unrelated donors in kidney transplants: better long-term results than with non-HLA-identical living related donors?

BACKGROUND: Given the severe organ shortage and the documented superior results obtained with living (vs. cadaver) donor kidney transplants, we have adopted a very aggressive policy for the use of living donors. Currently, we make thorough attempts to locate a living related donor (LRD) or a living unrelated donor (LURD) before proceeding with a cadaver transplant. METHODS: We compared the results of our LURD versus LRD transplants to determine any significant difference in outcome. RESULTS: Between 1/1/84 and 6/30/98, we performed 711 adult kidney transplants with non-HLA-identical living donors. Of these, 595 procedures used LRDs and 116 used LURDs. Immunosuppression for both groups was cyclosporine-based, although LURD recipients received 5-7 days of induction therapy (antilymphocyte globulin or antithymocyte globulin), whereas LRD recipients did not. LURD recipients tended to be older, to have inferior HLA matching, and to have older donors than did the LRD recipients (all factors potentially associated with decreased graft survival). Short-term results, including initial graft function and incidence of acute rejection, were similar in the two groups. LURD recipients had a slightly higher incidence of cytomegalovirus disease (P=NS). We found no difference in patient and graft survival rates. However, the incidence of biopsy-proven chronic rejection was significantly lower among LURD recipients (16.7% for LRD recipients and 10.0% for LURD recipients at 5 years posttransplant; P=0.05). LRD recipients also had a greater incidence of late (>6 months posttransplant) acute rejection episodes than did the LURD recipients (8.6% vs. 2.6%, P=0.04). The exact reason for these findings is unknown. CONCLUSION: Although LURD recipients have poorer HLA matching and older donors, their patient and graft survival rates are equivalent to those of non-HLA-identical LRD recipients. The incidence of biopsy-proven chronic rejection is lower in LURD transplants. Given this finding and the superior results of living donor (vs. cadaver) transplants, a thorough search should be made for a living donor-LRD or LURD-before proceeding with a cadaver transplant.

Adult↗

Cloning and characterization of dRFX, the Drosophila member of the RFX family of transcription factors.

The RFX family of transcription factors is characterized by a unique DNA binding domain. Five genes have been isolated in mammals, one gene in Caenorhabditis elegans and in the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae. Whereas the roles of the RFX genes are beginning to be understood in yeasts, no clear function has been reported in multicellular organisms, except for RFX5, the most divergent member of the family. To study the physiological role of RFX transcription factors using an alternative multicellular model, we report the isolation and characterization of the Drosophila RFX gene (dRFX). The fruit fly protein shares highly conserved domains with the mammalian factors RFX1 to 3 and is more closely related to this subgroup. It binds DNA with the same target specificity as mammalian factors RFX1 to 3. dRFX is located on chromosome III and we characterized the entire locus. dRFX expression was analyzed during embryogenesis. dRFX mRNAs are detected only in the peripheral nervous system and in the brain of the embryo.

Amino Acid Sequence↗

A cell-intrinsic timer that operates during oligodendrocyte development.

Multicellular organisms develop on a predictable schedule that depends on both cell-intrinsic timers and sequential cell-cell interactions mediated by extracellular signals. The interplay between intracellular timers and extracellular signals is well illustrated by the development of oligodendrocytes, the cells that make the myelin in the vertebrate central nervous system. An intrinsic timing mechanism operates in each oligodendrocyte precursor cell to limit the length of time the cell divides before terminally differentiating. This mechanism consists of two components, a timing component, which depends on the mitogen platelet-derived growth factor (PDGF) and measures elapsed time, and an effector component, which depends on thyroid hormone and stops cell division and initiates differentiation at the appropriate time. The cell-cycle inhibitor p27/Kip1 accumulates in the precursor cells as they proliferate and is part of both components of the timer. It seems likely that similar timing mechanisms operate in other cell lineages. BioEssays 22:64-71, 2000.

Animals↗

A survey of PCDD and PCDF in French long-life half-skimmed drinking milk.

A national survey was carried out in order to assess the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) in long-life half-skimmed drinking milk produced and consumed in France. 151 Samples were collected from 33 dairy establishments selected for their production amounts following a random sampling scheme. 148 of the 151 results were finally used for statistical assessment. The mean concentration of 2,3,7,8-TCDD toxicity equivalent found is 0.65 pg/g of milk fat. This result is far below the threshold recommended by the European Union.

Animals↗

An extended state-transition model for foot-and-mouth disease epidemics in France.

The dynamics of foot-and-mouth disease epidemics in France was examined through simulations based on an extended state-transition model. Contagion modelling depended on specific parameters: the so-called dissemination rates. Estimation of these parameters relied on a specific discrete-event simulation model. We were able to address the problem of the hidden spread of the epidemic, before the first outbreak is diagnosed. Furthermore, we took into account the silent development of the disease in affected herds before the diagnosis. The effect of control measures such as the active search for secondary outbreaks could thus be studied. We used the model to compare the development of FMD epidemics in two very different French regions and for different control strategies implemented by the animal-health authorities. These strategies gave similar results in a low herd density area, whereas in a high herd density area, the slaughter of contact herds greatly improved the stamping-out strategy. Finally, key parameters of the model were detected through a sensitivity analysis.

Animals↗

Simulated economic consequences of foot-and-mouth disease epidemics and their public control in France.

The efficient management of foot-and-mouth disease (FMD) epidemics in France was examined through a simulation model which combines epidemiological and economic modules. From the reactions of the importing countries in terms of the products subject to import bans and the regionalization commitments, the economic module assesses the financial consequences of FMD outbreaks borne not only by the breeding sector but also by the other economic sectors on regional and national levels. Among the control options for FMD, the strategy of stamping out infected herds and dangerous in-contact herds most often contributes to reducing the economic consequences of FMD epidemics. Implementing a campaign of emergency vaccination is socially optimal if the additional export losses associated with the delay of slaughtering the vaccinated animals are offset by the gains of reducing the duration of the FMD epidemic. The importance of reducing as much as possible the total duration of the import bans is stressed by the estimated cost of an extra week of import bans. The optimal control strategy was unaffected by the introduction of stochastic parameters.

Animals↗

An analysis of the early events when oligodendrocyte precursor cells are triggered to differentiate by thyroid hormone, retinoic acid, or PDGF withdrawal.

Oligodendrocyte precursor cells withdraw from the cell cycle and terminally differentiate after a limited number of cell divisions. The timing of cell-cycle withdrawal and differentiation is controlled by an intrinsic timer, which consists of a timing component that measures elapsed time and an effector component that arrests the cell cycle and initiates differentiation. The effector component can be triggered by either thyroid hormone (TH) or retinoic acid (RA). In this study we investigate how TH and RA act to trigger differentiation. We show the following: (1) Synthetic retinoids that can inhibit AP-1 transcription factors but do not activate gene transcription cannot trigger the effector mechanism, suggesting that TH and RA do not act only by inhibiting AP-1 activity as previously suggested. (2) Both TH and RA induce a transcriptionally dependent antigenic change in purified precursor cells within 2-4 h. (3) Unexpectedly, even before they differentiate, the precursor cells express ceramide galactosyltransferase (CGT), the enzyme that catalyzes the final step in the synthesis of galactocerebroside, an early marker of oligodendrocyte differentiation. (4) Neither TH nor RA directly activates the transcription of the CGT gene, a number of immediate early genes, or the genes that encode any of the known cyclin-dependent kinase inhibitors. (5) The withdrawal of the mitogen platelet-derived growth factor (PDGF), but not TH or RA treatment, causes a rapid decrease in c-fos, NGFI-A/Krox-24, and cyclin D2 mRNA, even though all three treatments trigger cell-cycle arrest and differentiation. (6) PDGF withdrawal and TH treatment, but not RA treatment, induce an increase in cyclin D3 mRNA within 4 h. Thus, we have not found any early changes in gene expression that occur with all three treatments that trigger oligodendrocyte differentiation.

Animals↗

Altered expression of cell cycle proteins and prolonged duration of cardiac myocyte hyperplasia in p27KIP1 knockout mice.

-The precise role of cell cycle-dependent molecules in controlling the switch from cardiac myocyte hyperplasia to hypertrophy remains to be determined. We report that loss of p27(KIP1) in the mouse results in a significant increase in heart size and in the total number of cardiac myocytes. In comparison to p27(KIP1)+/+ myocytes, the percentage of neonatal p27(KIP1)-/- myocytes in S phase was increased significantly, concomitant with a significant decrease in the percentage of G(0)/G(1) cells. The expressions of proliferating cell nuclear antigen, G(1)/S and G(2)/M phase-acting cyclins, and cyclin-dependent kinases (CDKs) were upregulated significantly in ventricular tissue obtained from early neonatal p27(KIP1)-/- mice, concomitant with a substantial decrease in the expressions of G(1) phase-acting cyclins and CDKs. Furthermore, mRNA expressions of the embryonic genes atrial natriuretic factor and alpha-skeletal actin were detectable at significant levels in neonatal and adult p27(KIP1)-/- mouse hearts but were undetectable in p27(KIP1)+/+ hearts. In addition, loss of p27(KIP1) was not compensated for by the upregulation of other CDK inhibitors. Thus, the loss of p27(KIP1) results in prolonged proliferation of the mouse cardiac myocyte and perturbation of myocyte hypertrophy.

3T3 Cells↗

Impregnated polyester arterial prostheses: performance and prospects.

Impregnated polyester arterial prostheses have gained wide acceptance by most vascular surgery teams, probably because these prostheses are easy to use, without any preclotting. We offer here a synthesis of the main studies that have appraised the experimental and clinical performance of these prostheses, and we delineate their major prospects.

Animals↗

Influence of crimping textile polyester vascular prostheses on the fluid flow kinetics. Groupe Européen de Recherche sur les Prothèses appliquées à la Chirurgie Vasculaire.

OBJECTIVES: to characterise the impact of the crimping of polyester prostheses on the fluid flow kinetics. DESIGN: an experimental in vitro study. MATERIALS AND METHODS: we investigated four models of polyester vascular prostheses in a continuous laminar flow circuit. The flow velocity was 80 ml/s for all experiments. We studied two fluids of different viscosity within the circuit. The speed of the particles was measured by a laser Doppler anemometer 2 to 52 mm from the prosthetic interface. We first established a calibrated flow-velocity profile corresponding to the study of the support inside the circuit without any prosthesis. We measured the velocity profiles for each prosthesis corresponding to four crimp densities obtained by stretching the grafts. RESULTS: the crimping of PET textile prostheses led to a decrease of flow velocity especially closer to the prosthetic surface. The decrease of flow velocity was dependent on the model of prosthesis. This decrease of flow velocity is described by the following negative exponential law: DeltaV=a times b(-x)where (a) is the crimp density and (b) the fluid viscosity. CONCLUSIONS: flow velocity near a prosthetic surface is influenced by the morphology of the crimping. The impact of crimping on the flow velocity in a vascular prosthesis can be predicted by computer simulation models. This may provide the optimal shape of crimping for each prosthesis.

Blood Flow Velocity↗

p27Kip1 alters the response of cells to mitogen and is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation.

BACKGROUND: In many vertebrate cell lineages, precursor cells divide a limited number of times before they arrest and terminally differentiate into postmitotic cells. It is not known what causes them to stop dividing. We have been studying the 'stopping' mechanism in the proliferating precursor cells that give rise to oligodendrocytes, the cells that make myelin in the central nervous system. We showed previously that the cyclin-dependent kinase inhibitor p27Kip1 (p27) progressively accumulates in cultured precursor cells as they proliferate and that the time course of the increase is consistent with the possibility that p27 accumulation is part of a cell-intrinsic timer that arrests the cell cycle and initiates differentiation at the appropriate time. RESULTS: We now provide direct evidence that p27 is part of the intrinsic timer. We show that although p27-/- precursor cells stop dividing and differentiate almost as fast as wild-type cells when deprived of mitogen, when stimulated by saturating amounts of mitogen they have a normal cell-cycle time but tend to go through one or two more divisions than wild-type cells before they stop and differentiate. Cells that are p27+/- behave in an intermediate way, going through at most one extra division, indicating that the levels of p27 matter in the way the timer works. We also show that p27-/- precursor cells are more sensitive than wild-type cells to the mitogenic effect of platelet-derived growth factor. CONCLUSIONS: These findings demonstrate that p27 is part of the normal timer that determines when oligodendrocyte precursor cells stop dividing and differentiate, at least in vitro. It seems likely that p27 plays a similar role in many other cell lineages, which could explain the phenotypes of the p27-/- and p27+/- mice.

Animals↗

Sinusitis-associated epidural abscess presenting as posterior scalp abscess--a case report.

Complications of paranasal sinusitis constitute true surgical and medical emergencies. These complications appear to be more prevalent and seem to present in a more fulminant manner in the pediatric age group. The most common complication of paranasal sinusitis is orbital cellulitis followed collectively by all the intracranial complications. These include meningitis, subdural empyema, intracerebral abscess, epidural abscess and rarely cavernous or superior sagittal sinus thrombosis. We report the case of a 7-year old boy who presented with posterior scalp cellulitis and abscess as a complication of minimally symptomatic paranasal sinusitis. A combined neurosurgical and otolaryngologic approach was required to treat a unilateral ethmoid and frontal sinusitis associated with an epidural abscess abutting the length of the superior sagittal sinus and a posterior subgaleal abscess. The pertinent anatomy allowing for the development of this disease process is discussed. The danger of neurologic sequellae resulting from thrombosis of the superior sagittal sinus is emphasized. Aggressive treatment utilizing a multi-disciplinary surgical approach as well as broad spectrum antibiotics is paramount to obtain the best chance for a full recovery.

Abscess↗

Generation of stable monocyte-derived dendritic cells in the presence of high concentrations of homologous or autologous serum: influence of extra-cellular pH.

Recent studies have highlighted the high degree of differentiation of monocytes. Indeed, dendritic cells (DC) can be generated from monocytes, in the presence of appropriate cytokines. However, human serum is usually avoid in such cultures. Here, we report that human serum does not inhibit generation of mature DC from blood monocytes, but rather that extra-cellular pH may play an important role in the regulation of monocyte differentiation. Indeed, monocytes cultured at pH 7.4 in the presence of high concentrations of human serum developed efficiently into mature DC, as opposed with monocytes cultured at pH 7. These pH 7.4 cultured DC presented features characteristic of mature DC, at the phenotypical, functional and morphological levels. In addition, these DC were stable, with respect to their sustained expression of CD83 and CD86, upon withdrawal of cytokines. Finally, when autologous plasma was used instead of homologous serum, differentiation of monocytes into mature DC was efficient, as well. Thus, altogether, our data show the importance of extra-cellular pH on differentiation of monocyte-derived DC in the presence of human serum, which should be maintained at plasma levels.

Antigens, CD↗

Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies.

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma (n = 148), Hodgkin's disease (n = 22) and multiple myeloma (n = 30). The variables predicting the collection of a minimal (>2.5 x 10(6)/kg) or a high (>10 x 10(6)/kg) CD34+ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy (n = 49) or high-dose cyclophosphamide, given alone (n = 55) or combined with high-dose VP16 (n = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34+ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count (P=0.06 and 0.0008 respectively). The target to collect a high CD34+ cell count was negatively associated with the number of previous chemotherapy regimens (P=0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield (P=0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.

Adolescent↗

Cell number control and timing in animal development: the oligodendrocyte cell lineage.

Our studies of oligodendrocyte development in the rodent optic nerve provide clues as to how cell numbers and the timing of differentiation may be controlled during mammalian development. Both cell number and the timing of differentiation depend on intracellular programs and extracellular signals, which together control cell survival and cell division. As the cells seem to compete for limiting amounts of both survival signals and mitogens, the levels of these extracellular signals must be tightly regulated, but it is not known how this is achieved. The timing of cell-cycle exit, and therefore the onset of differentiation, seems to depend in part on the progressive accumulation of the intracellular Cdk inhibitor p27/Kip1, but it is still unclear how the level of this protein is controlled over time in the dividing cells. The timing of cell-cycle exit is also regulated by thyroid hormone, which, along with other hormones, seems to coordinate the timing of development in various organs, much as the timing of the multiple changes in metamorphosis in both vertebrates and invertebrates is coordinated by hormones. In this sense, one might think of mammalian development as a prolonged metamorphosis.

Animals↗

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency.

Major Histocompatibility Complex class II (MHC-II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC-II genes. Cell lines from MHC-II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC-II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC-II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA). This establishes that group D is indeed a fourth MHC-II deficiency complementation group. Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene.

Amino Acid Sequence↗