Search PubMed⌕ Search

Biomedical subjects

E Dupont

Publications and source records attributed to E Dupont.

At least 91 records · Page 5Linked to original sources
PubMed1995

Influence of donor-recipient HLA-DR mismatches and OKT3 prophylaxis on cadaver kidney graft survival.

Previous studies from our center have shown that donor-recipient HLA-DR mismatches (MM), characterized by the presence of the DR antigen in the donor but not in the recipient or vice versa, are associated with differential effects on graft survival (GS): some of them are beneficial (BEN) with results similar to those of HLA-DR identical or compatible pairs (85% 18 months GS) and some are detrimental (DET) (64% 18 months GS), whereas the other MM, neither BEN nor DET (neutral [NEU]) yield intermediate results (78% 18 months GS). The aim of the present study was to update the results at a longer follow-up time and to assess whether they are influenced or not by prophylactic administration of anti-CD3 mAb (OKT3). The analysis of 234 transplantations performed from 1980 to 1994 with only 1 HLA-DR MM confirmed the BEN effects of HLA-DR5 in either the donor or the recipient and the DET effects of HLA-DR1 or -DR2 in the donor and of HLA-DR2 or -DRW6 in the recipient. These effects were independent of those exerted by other, HLA-DR not related, prognostic factors. The transplants with 1 HLA-DR MM were then compared with those with zero HLA-DR MM (n = 378) and 4 groups were formed according to 2 levels of HLA-DR MM (zero or BEN MM vs. NEU or DET MM) and immunosuppression (with vs. without OKT3 prophylaxis). GS at 5 years was 63% in the group with either zero or BEN MM as compared with 41% in the group with either NEU or DET MM in the absence of OKT3 prophylaxis (P < 0.02); in comparison, with OKT3 prophylaxis, GS at 5 years was 73% in the group with either zero or BEN MM as compared with 58% in the group with either NEU or DET MM (P = 0.07). We conclude that the differential effects of HLA-DR MM on GS are still observed under OKT3 prophylaxis, that the effects of HLA-DR and immunosuppression on graft outcome are additive, and that OKT3 induction therapy is superior to therapy without OKT3. These observations could have important implications for the allocation policy and management of renal transplants.

Adult↗
PubMed1995

[Hemifacial spasms--clinical picture, diagnosis and treatment].

A rectrospective study of 23 consecutive patients with hemifacial spasm is presented. Based on this experience, a practical approach to the diagnosis, investigation and treatment with injections of botulinum toxin is described. Magnetic resonance imaging angiography of the brain was performed in 20 patients an 15 controls. Contact between an artery from the vertebrobasilar circulation and the intracranial part of the facial nerve was observed ipsilaterally to the spasm in 17 patients (85%) and in two controls (7%). Treatment with botulinum toxin was performed in 16 patients with moderate to good improvement in the majority of the patients. MR-angiography is recommended in order to exclude infrequent etiologies and as preoperative evaluation. Botulinum toxin injection is recommended as the symptomatic treatment of choice. The possibility of curative surgical intervention by microvascular decompression of the facial nerve is discussed.

Adult↗
PubMed1995

Identification of a neural-specific cDNA, NPDC-1, able to down-regulate cell proliferation and to suppress transformation.

Immortalized neural precursor cell lines carrying the polyoma large tumor (T) gene have been shown previously to retain a clear-cut contact inhibition of growth and to differentiate in vitro. In the present study, we have identified and isolated cDNA clones corresponding to RNA expressed preferentially when these cells reach confluence. One of them, NPDC-1, is expressed specifically in the nervous system. The transfection of dividing cells with a NPDC-1 expression vector results in the inhibition of cell proliferation. In addition, the stable introduction of NPDC-1 into transformed cells, even of nonneural origin, leads to the suppression of transformed characteristics.

Amino Acid Sequence↗
PubMed1995

Antistaphylococcal activity of rifampin-bonded gelatin-impregnated Dacron grafts.

The affinity of rifampin to bond to Dacron permits implantation of a vascular prosthesis with anti-staphylococcal bioactivity. The performance of rifampin-bonded Dacron grafts was evaluated in vitro and in vivo to develop a bonding technique with optimal graft bioactivity which was then used for in situ reconstruction of a biofilm graft infection. In vitro bioactivity was measured at 24-hr intervals for three types of Dacron prostheses (plain, gelatin, and collagen-impregnated) exposed to rifampin at varied concentrations and immersion times. Gelatin-impregnated grafts demonstrated superior bioactivity (P < 0.05). Rifampin concentration and graft type had a greater effect on bioactivity than immersion time (P < 0.01). Gelatin-impregnated grafts immersed in a 60 mg/ml rifampin solution for 15 min produced optimum bioactivity. Six grafts prepared in this fashion were used to replace the canine aorta. The level and duration of in vivo antistaphylococcal activity to Staphylococcus aureus and Staphylococcus epidermidis were less (P < 0.05) than those measured in vitro, but rifampin levels exceeded the study strain maximum inhibitory concentration for up to 48 hr. In a canine model, the rifampin-bonded gelatin-impregnated (N = 14) or nonbonded control (N = 10) grafts were used as in situ replacement for an established aortic graft infection caused by S. epidermidis. Replacement with a rifampin-bonded graft resulted in successful anatomic healing of perigraft and anastomotic tissue. Persistent biofilm colonization was confirmed in 8 of 10 controls versus 4 of 14 rifampin-bonded grafts (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Interleukin 12 unmasks HLA class I differences during mixed lymphocyte reaction induced interferon gamma production.

We investigated the genetic control of IFN-gamma release during MLR and its relationship with TNF-alpha and IL-12. Blocking experiments demonstrated the IFN-gamma dependence of TNF-alpha production and the significant contribution of IL-12 to IFN-gamma secretion. We studied informative pairs allowing the evaluation of the relative importance of HLA class I and class II antigens. Maximal IFN-gamma secretion allowing discrimination between fully HLA different and identical subjects required 5 days. In class I different but DRB1 identical pairs, a moderate but discriminant IFN-gamma release was found. Exogenous IL-12 addition after 24 hours of preactivation by MLR resulted in a marked enhancement of IFN-gamma production at day 2. In pairs differing only by class I antigens, the discriminating capacity was significantly increased as compared to values obtained in absence of IL-12 at day 2 (p < 0.004) and at day 5 (p < 0.004). The crucial role of class I antigens on IFN-gamma release was further substantiated by the blocking action of the W6/32 mAb directed against a monomorphic epitope common to all HLA-A, -B, and -C antigens. We conclude that IFN-gamma production during MLR is under the control of class I antigens. Furthermore, exogenous IL-12 strongly amplifies their influence.

HLA Antigens↗
PubMed1995

In vitro inhibition of tumour necrosis factor-alpha and interleukin-6 production by intravenous immunoglobulins.

In vitro data about the action of pooled immunoglobulins (Ig) on cytokine (CK) production are controversial. The recent finding of natural antibodies against staphylococcal toxins neutralizing superantigen-induced activation prompted us to design an assay determining their ability to modulate staphylococcal enterotoxin B (SEB) induced CK production (IL-6 and TNF-alpha). Presence of anti-SEB antibodies was demonstrated by a dot-blot assay in the three preparations tested. Preincubation of SEB with pooled Ig prior to addition into the test tube containing PBMCs (neutralizing condition) resulted in a strong inhibition of both TNF-alpha and IL-6 release (TNF alpha: 59 +/- 5% inhibition, P < 0.0001; IL-6: 71 +/- 7% inhibition, P < 0.0001, n = 15). Anti-CD3 MoAb-induced CK production was not modified. During our study it was found that experimental conditions were critical to observe this inhibitory effect. Reversing the previous procedure by adding PBMCs into the test tube containing pooled Ig mixed with SEB resulted in a marked induction of TNF-alpha and IL-6 production. The same observation was made when pooled Ig solely was added (coating condition). F(ab')2 fragments of pooled Ig displayed similar inhibitory capacity when added in neutralizing condition, indicating that the mechanism involved was not Fc dependent. The fragments lost the activating properties of intact Ig when incubated in coating condition, showing that Fc receptor activation occurs in this setting. The present work demonstrates that inhibition of SEB-induced CKs release by pooled Ig can be achieved by SEB neutralization, provided that the experimental conditions avoid activation through the Fc receptor. It can be assumed that similar mechanisms take place in some clinical conditions during which pooled Ig are infused.

Cell Division↗
PubMed1995

Pen injected apomorphine against off phenomena in late Parkinson's disease: a double blind, placebo controlled study.

The effect, therapeutic dose range, and pharmacokinetics of apomorphine, given as subcutaneous injections by a single use pen, were evaluated in the treatment of off phenomena in 22 patients with idiopathic Parkinson's disease. At study entry a placebo controlled apomorphine test was performed, and apomorphine doses were then individually titrated (mean 3.4 (range 0.8-6.0) mg) and compared with placebo in a double blind cross over phase. With apomorphine compared with placebo the mean daily duration of off periods was reduced by 51% as assessed by the patients and by 58% as assessed by the staff. The severity of off periods was also significantly reduced. The effect was unchanged after a maintenance phase of eight weeks. At study termination 13 of 14 patients were able to inject themselves and 11 of 14 patients found that their feeling of freedom had increased. The most common adverse events were nausea, subcutaneous nodules, and increased frequency of involuntary movements. Pharmacokinetics were linear and did not change with repeat dosing. The tmax ranged from five to 45 minutes (16 patients). It is concluded that pen injected apomorphine is a valuable treatment for patients with advanced Parkinson's disease with on-off phenomena.

Adult↗
PubMed1995

[Novel autograft method using positive selection of CD34 stem cells].

High dose chemotherapy with autologous blood stem cell rescue becomes widely used for patients with hematologic malignancies and solid tumors. Recently, it has been demonstrated that stem cells characterized by the CD34 antigenic marker could be positively selected using an anti CD34 monoclonal antibody and an avidin biotin immunoabsorption device. We report our experience of twelve selections and ten grafts. A CD34+ cells enrichment of 1.9 log (purity: 72%) and a CFU-GM cells concentration of 1.6 log have been obtained. In ten transplanted patients, the hematological recovery was similar to that obtained with non selected blood stem cells. The CD34+ cells purification allows mini graft infusion and purge of residual tumor cells implicated in relapse after autologous stem cells transplantation.

Adult↗
PubMed1994

Optimal blood stem cell mobilization using 10 micrograms/kg granulocyte colony-stimulating factor (G-CSF) alone for high-dose melphalan intensification in multiple myeloma: an intrapatient controlled study.

A recent randomized multicentric French study has shown that intensification with stem cell rescue improves the response rate and progression-free survival in multiple myeloma. Transplantation with primed peripheral blood stem cells (PBSC) displays a faster hematological recovery, especially for platelets, as compared with a bone marrow stem cell graft. In multiple myeloma, the optimal mobilization method for PBSC is unknown. The present study compares mobilization with cyclophosphamide 4 g/m2 + G-CSF 5 micrograms/kg versus G-CSF 5 micrograms/kg alone versus G-CSF 10 micrograms/kg alone in two cases of multiple myeloma, using an intrapatient controlled evaluation of the amount of CD34-positive cells obtained during each leukapheresis. In both cases, the highest CD34-positive cells yield was obtained with G-CSF at 10 micrograms/kg. Despite the low number of cases, this method, devoid of life-threatening toxicity, might be of greatest interest in multiple myeloma.

Antigens, CD↗
PubMed1994

Tumor necrosis factor and intravenous gammaglobulins in common variable immunodeficiency.

Common variable immunodeficiency (CVI) patients require regular intravenous immunoglobulin substitution therapy (IVGG). We studied eight patients; four of whom had adverse reactions to IVGG, and found that those coincided with elevated tumor necrosis factor-alpha (TNF-alpha) levels during infusion. Those reactions and TNF production were abolished by switching from one IVGG preparation to another in two patients. Reappearance of adverse reactions after switching preparation was preceded by a progressive rise in peak TNF levels in one patient.

Adolescent↗
PubMed1994

Localization of 3 beta-hydroxysteroid dehydrogenase in rat brain as studied by in situ hybridization.

Recent evidence suggests that brain cells can synthesize steroids de novo. The steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene family of enzymes is involved in the biosynthesis of all classes of active steroids. In the present study, we have used in situ hybridization performed with a 35S-labeled cDNA-encoding rat type I 3 beta-HSD to localize the expression of member(s) of this gene family in the adult rat brain. A specific hybridization signal could only be detected in a restricted area of the medulla ventrally and laterally bordering the fourth ventricle. This area contains the nucleus propositus hypoglossi as well as some vestibular nuclei: the nucleus vestibularis medialis, the nucleus vestibularis lateralis, and the nucleus vestibularis spinalis. At high resolution, the silver grains representing a hybridization signal were detected exclusively in neurons. The present data strongly suggest that a restricted population of neurons might be involved in steroid biosynthesis in the adult rat brain. The role of the member(s) of the rat 3 beta-HSD family in the nuclei of two cranial nerves remains to be investigated.

3-Hydroxysteroid Dehydrogenases↗
PubMed1994

Loss of gap junctions from DDT-treated rat liver epithelial cells.

The mechanism by which the liver tumor promoter 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) inhibits gap junctional intercellular communication (GJIC) in WB-F344 rat liver epithelial cells could involve gap junction loss and/or decreased gap junction channel permeability. We examined these two possibilities in the present study. Immunohistochemical studies using antibodies specific to connexin43, the major gap junction protein expressed by these cells, revealed that gap junction number and size were reduced during exposure to DDT. The reductions in gap junctions (33-91%) correlated with dose-dependent (1-10 microM) and time-dependent (0.5-4 h) decreases in cell-to-cell fluorescent dye-coupling (64-85%), as well as cellular levels of phosphorylated connexin43. These effects were reversible following removal of the tumor promoter from the culture medium, although cycloheximide reduced the level of gap junction reformation. The losses in gap junctions were not due to decreased connexin43 gene expression since steady-state levels of connexin43 mRNA were not similarly affected by DDT. Fenarimol (10 microM), a structural analog of DDT, did not inhibit GJIC and had no effect on gap junction structure or connexin43 expression. These data suggest that the inhibition of GJIC by DDT resulted from the removal of gap junctions from the plasma membrane and their degradation rather than simply a decrease in their permeability.

Animals↗
PubMed1994

Topography of mammalian connexins in human skin.

We have explored the expression of gap junction proteins in normal human skin by immunostaining cryostat sections (indirect immunofluorescence) or lyophilized epidermis (Western blotting) with antibodies against four mammalian connexins Cx26, Cx32, Cx40, Cx43; and by hybridizing total epidermal RNA (Northern blotting) with cRNA probes for Cx26, Cx32, and Cx43. We found that epidermal keratinocytes express Cx43 but not Cx26, Cx32, or Cx40. This expression was minimal in the basal layer, much higher in the spinous layer, reduced in the granular layer, and absent in the stratum corneum. Immunostaining for Cx43 was also observed in sebaceous glands, hairs, and eccrine sweat ducts. The two latter epidermal adnexae were also markedly labeled by antibodies against Cx26, a gap junction protein that was undetectable by immunofluorescence in interfollicular keratinocytes. Immunoblots of polyacrylamide gel electrophoresis-separated epidermal proteins and hybridization of epidermal RNA confirmed the presence of Cx43 in epidermis. These observations indicate that 1) Cx43 and Cx26 are components of human keratinocyte gap junctions; 2) these two proteins are differentially expressed in the interfollicular epidermis and the skin adnexae; 3) in interfollicular epidermis, Cx43 is a predominant gap junction protein, mostly expressed by the differentiating spinous cells; 4) Cx43 distribution is in accordance with the extensive dye coupling previously observed in this epidermal compartment.

Animals↗
PubMed1994

Bedside transfusion errors. A prospective survey by the Belgium SAnGUIS Group.

The true incidence of bedside transfusion errors, i.e. those happening when blood products have left the blood bank, is underestimated because published figures rely on reporting of clinically relevant events or on indirect methods. The SAnGUIS project assessing blood practice in a prospective and randomized fashion for 6 elective surgical procedures gave the opportunity to trace all transfused units and to identify steps at risk during blood delivery in surgery. We considered transfusion of a wrong unit as a major error and poor execution or documentation as a recording error. Over 15 months, 808 patients out of 1,448 were transfused with 3,485 units. A total of 165 errors were found after blood products had left the blood banks. Seven were misidentifications (0.74% of patients, 0.2% of units). Eight other major errors occurred in 4 (0.5%) patients. Major errors occurred during nonemergency situations, in wards or intensive care units. The remaining ('recording') 150 errors consisted of misrecordings (61), mislabellings (6), or failures to document transfusions in the medical records (83). All errors were uneventful except one misidentification which induced a transient, yet unreported, reaction. The 'descending' inquiry method used for this study showed that most errors pass unnoticed and are therefore not reported. Measurement of error rates may constitute an important quality indicator. Retrospective information of this survey to the concerned staff people provided an impetus to take adequate measures to reduce these bedside errors.

Belgium↗
PubMed1994

Clinical diagnosis of Parkinson's disease. Proposal of diagnostic subgroups classified at different levels of confidence.

The objective of this paper is to evaluate the accuracy of conventional diagnostic criteria for Parkinson's disease and give an overview of alternative causes to parkinsonian syndromes. We also propose a new approach to the clinical diagnosis of Parkinson's disease, which may improve the diagnostic accuracy. The available information on autopsy findings in patients clinically diagnosed as Parkinson's disease shows that 20 to 30% of these patients do not have the typical neuropathological features with Lewy bodies and cell loss in the substantia nigra. The use of selected additional clinical criteria improves the diagnostic accuracy, however, at the cost of rejecting a rather large group of patients with idiopathic disease verified by autopsy. Based on this fact and a review of the literature on parkinsonian syndromes that may be confused with idiopathic Parkinson's disease, we propose criteria for diagnostic subgroups of the disease classified at different levels of confidence. The suggested diagnostic subgroups are clinical definite, probable and possible Parkinson's disease with a decreasing level of specificity and an increasing level of sensitivity in the different patient categories. The clinical features given special importance in this classification includes presence of resting tremor, asymmetrical disease, response to dopamine agonism and presence of atypical clinical features like dementia and clinical autonomic failure at onset and pyramidal or cerebellar signs at examination. In addition, a history indicating possible etiology for another parkinsonian syndrome will exclude the diagnosis.

Diagnosis, Differential↗
PubMed1994

Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus.

Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.

Amino Acid Metabolism, Inborn Errors↗