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B Dubois

Publications and source records attributed to B Dubois.

At least 73 records · Page 4Linked to original sources
PubMed2001

Selective attraction of naive and memory B cells by dendritic cells.

In this study, we investigate whether dendritic cells (DC), known to interact directly with T and B cells, might also contribute to the recruitment of B cells through the production of chemotactic factors. We found that B cells responded to several chemokines (CXCL12, CCL19, CCL20, and CCL21), which can be produced by DC upon activation. In addition, supernatant from DC (SNDC) potently and selectively attracted naive and memory B cells but not germinal center (GC) B cells or other lymphocytes (CD4(+), CD8(+) T cells or NK cells). Production of this activity was restricted to DC and was not increased following DC activation by LPS or CD40 ligand. Surprisingly, the B-cell chemotactic response to SNDC was insensitive to pertussis toxin treatment. In addition, the chemotactic factor(s) appeared resistant to protease digestion and highly sensitive to heat. This suggested that the DC chemotactic factor(s) is different from classical chemoattractants and does not involve G(alpha(i)) proteins on the responding B lymphocytes. It is interesting that SNDC was able to synergize with several chemokines to induce massive migration of B lymphocytes. These observations show that DC spontaneously produce factors that, alone or in cooperation with chemokines, specifically regulate B-cell migration, suggesting a key role of DC in the recruitment or localization of B lymphocytes within secondary lymphoid organs.

B-Lymphocytes↗
PubMed2001

[Procedural learning and Parkinson disease: implication of striato-frontal loops].

OBJECTIVE: To investigate procedural learning in non demented patients with idiopathic Parkinson's disease (PD). BACKGROUND: Experimental evidence implicate the basal ganglia in procedural learning. Selective impairment has more recently been described in patients with frontal lesions. METHODS: The performance of 20 demented patients and 15 matched normal controls was studied in the serial reaction time task (SRTT). Performance on procedural task was further compared with that of 9 normal controls and with patients' performance on tests assessing explicit memory, executive functions and global efficiency. RESULTS: The group of patients with PD showed impaired procedural learning. The difference of response time between the repeated and the non-repeated blocks was smaller in PD when compared to controls. Subsequent analyses separated PD patients into two subgroups according to their performance on SRTT, measured by the rebound effect. PD patients whose learning was normal differed from PD patients whose learning was impaired on performance in tests sensitive to frontal lobe dysfunction. CONCLUSION: These results confirm the implication of the striatum in procedural learning and suggest that performance on cognitive procedural learning depends on the striato-frontal circuits.

Aged↗
PubMed2000

The FAB: a Frontal Assessment Battery at bedside.

OBJECTIVE: To devise a short bedside cognitive and behavioral battery to assess frontal lobe functions. METHODS: The designed battery consists of six subtests exploring the following: conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. It takes approximately 10 minutes to administer. The authors studied 42 normal subjects and 121 patients with various degrees of frontal lobe dysfunction (PD, n = 24; multiple system atrophy, n = 6; corticobasal degeneration, n = 21; progressive supranuclear palsy, n = 47; frontotemporal dementia, n = 23). RESULTS: The Frontal Assessment Battery scores correlated with the Mattis Dementia Rating Scale scores (rho = 0.82, p < 0.01) and with the number of criteria (rho = 0.77, p < 0.01) and perseverative errors (rho = 0.68, p < 0.01) of the Wisconsin Card Sorting Test. These variables accounted for 79% of the variance in a stepwise multiple regression, whereas age or Mini-Mental State Examination scores had no significant influence. There was good interrater reliability (kappa = 0.87, p < 0.001), internal consistency (Cronbach's coefficient alpha = 0.78), and discriminant validity (89.1% of cases correctly identified in a discriminant analysis of patients and controls). CONCLUSION: The Frontal Assessment Battery is easy to administer at bedside and is sensitive to frontal lobe dysfunction.

Adult↗
PubMed2000

Mitochondrial mutations of Leber's hereditary optic neuropathy: a risk factor for multiple sclerosis.

Multiple sclerosis (MS) and Leber's hereditary optic neuropathy (LHON) have been found to occur in combination. Based on an extensive literature search and on a clinical analysis of 55 LHON pedigrees (103 patients) and 40 patients with definite MS, this study concludes that the association of LHON and MS is more than a coincidence, and that carrying a primary LHON mutation is a risk factor for developing MS. All three primary LHON mutations occurring in the European and North American populations have been found to be associated with an MS-like syndrome. The neurological characteristics of MS associated with LHON are indistinguishable from those of MS in general, but the severe and bilateral visual symptoms and signs justify considering these patients as a clinical subgroup of MS and screening them for LHON mutations. However, screening LHON patients for MS appears to be more rewarding.

Adult↗
PubMed2000

How patients with Parkinson's disease retrieve and manage cognitive event knowledge.

Several studies have pointed out that basal ganglia are involved in adaptive control of action at both motor and cognitive level. This study aimed to investigate how basal ganglia retrieve and manage script event knowledge required in planning behavior. Script event knowledge was investigated in patients with Parkinson's Disease using three kinds of activity that differed in familiarity. Unlike patients with prefrontal lesions, patients with Parkinson's Disease were able to order events in a typical sequence and obeyed the boundaries and hierarchies between events. In contrast, patients with Parkinson's Disease were impaired in evaluating how important each script event was within the context of goal-oriented planning activity. Our findings indicate that the prefrontal cortex and the basal ganglia are differentially involved in planning. The role of the basal ganglia might consist in providing a feedback about the goodness of each action while building up meaningful sequences of events during learning.

Adult↗
PubMed2000

An ecological approach to planning dysfunction: script execution.

Planning, which concerns many activities in everyday life, is a two-stage process. The first one predetermines a course of actions aimed at achieving some specific goals. It is founded on managerial knowledge or overlearned sequences of events and may be tested by script generation. The second stage entails monitoring and guiding the execution of the plan to a successful conclusion. It must take into account environmental contingencies and may be tested by script execution. If the frontal lobes intervene not only in managerial knowledge (Grafman, 1989) but also in binding the plan with contextual environment (Damasio, Tranel and Damasio, 1991; Shallice and Burgess, 1991), script execution would be more sensitive than script generation to planning deficits. To test this hypothesis, script execution and script generation were compared in 11 patients with a dysexecutive syndrome and 10 matched controls, using three scripts of daily life activities: (1) 'shopping for groceries'; (2) 'cooking'; (3) 'answering a letter and finding the way to post the reply'. Two way ANOVAs showed more errors in execution than in generation, more errors in patients than in controls, and a greater difference between execution and generation in patients than in controls. Furthermore, 'context neglect' and 'environmental adherence' were the two types of errors that best differentiated patients from controls. Finally, the total number of errors in execution correlated with the score on behavioral questionnaires answered by occupational therapists. These results confirm our hypothesis and suggest that script execution may be a valid ecological approach to estimate the severity of deficits in daily life activities.

Activities of Daily Living↗
PubMed2000

Human genetic factors related to susceptibility to mild malaria in Gabon.

Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF-alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum.

ABO Blood-Group System↗
PubMed2000

Diagnosis and management of Alzheimer's disease and other disorders associated with dementia. The role of neurologists in Europe. European Federation of Neurological Societies.

In 1998 a task force to develop guidelines for diagnostic evaluation and treatment of dementia was initiated by the European Federation of Neurological Societies (EFNS) scientist panel on dementia. The aims of the task force were to provide evidence-based recommendations and to highlight the role of the neurologist in the management of patients with Alzheimer's disease and other disorders associated with dementia. We based our recommendations on a review of available evidence-based guidelines supplemented with further literature reviews. The recommendations were derived from consensus meetings and relate to individual patient management, as there are inadequate data on the cost-effectiveness of different diagnostic evaluations and treatments for dementia. Their specific applications will depend upon available resources. The particular contributions of the neurologist include: early identification and differential diagnosis of rare and common brain disorders causing cognitive and behavioural symptoms, referral for and interpretation of ancillary investigations, and identification and treatment of vascular and other concurrent diseases. A review of the management of dementia in Europe revealed considerable variation. In some countries neurologists have taken the lead in the management of patients with dementia, while in other countries the neurologist is rarely involved. We recommend that neurologists should have a clear role in the management of dementia in the whole of Europe. They should be involved in the diagnostic evaluation of dementia and facilitate the development of multidisciplinary teams for evaluation and management of patients with cognitive disturbances. The increasing role of neurology in the management of patients with dementia has important implications for training and education.

Alzheimer Disease↗
PubMed2000

Similar subcortical pattern of cognitive impairment in AIDS patients with and without dementia.

The aim of this study was to develop a series of neuropsychological tests that define the cortical and subcortical features of cognitive impairment and the characteristics of memory in demented and mildly cognitively impaired AIDS patients. We attempted to establish a usable method to assess and determine the type and degree of cognitive impairment in individual AIDS patients. We examined 53 patients without central nervous system opportunistic infections. A short battery included two scales of global efficiency (the Mattis dementia rating scale and the Mini Mental State Examination), a psychomotor speed test, an executive control assessment and explicit memory evaluation. Patients were categorized into four groups based on their score on both the Mattis dementia rating scale and the DSM-IV criteria: (1) asymptomatic; (2) having AIDS without cognitive impairment; (3) having AIDS with mild cognitive impairment; and (4) having AIDS dementia. Patients with mildly impaired cognition demonstrated slowed thinking, abnormal initiation and conceptualization, and memory impairment. AIDS dementia patients had slower motor activity and memory recall was more severely affected. The short neuropsychological battery was able to characterize modified cognitive performances in both severely and mildly cognitively impaired AIDS patients. The subcortical pattern of the memory disorder was obvious, regardless of the degree of cognitive impairment.

AIDS Dementia Complex↗
PubMed2000

In vivo neutrophil recruitment by granulocyte chemotactic protein-2 is assisted by gelatinase B/MMP-9 in the mouse.

Granulocyte chemotactic protein-2 (GCP-2) of the mouse is a potent neutrophil chemotactic and activating factor in vitro and in vivo. Gelatinase B/matrix metalloproteinase-9 is released from neutrophils within 1 h after stimulation with GCP-2. In vitro neutrophil chemotaxis by GCP-2 was not impaired by specific inhibitory monoclonal antibodies (mAb) against gelatinase B, indicating that gelatinase B is not involved in chemotaxis of neutrophils through polycarbonate filters. To investigate if gelatinase B degranulation is involved in in vivo cell migration toward GCP-2, experiments were performed with gelatinase B knockout mice. When mouse GCP-2 was injected intradermally in mice, a dose-dependent neutrophil chemotactic response was observed, and this cell migration was significantly impaired in young mice by genetic gelatinase B knockout. In adult vs. young gelatinase B-deficient mice, such compensatory mechanisms as higher basal neutrophil counts and less impairment of chemotaxis toward local GCP-2 injection were observed. These experiments prove the concept that gelatinase B release under pressure of GCP-2 is a relevant, but not exclusive, effector mechanism of neutrophil chemotaxis in vivo and that known mechanisms, other than the release of gelatinase B, allow for a full-blown chemotactic response and compensate for gelatinase B deficiency in adult life in the mouse.

Aging↗
PubMed2000

The impact of metrifonate therapy on caregivers of patients with Alzheimer's disease: results from the MALT clinical trial. Metrifonate in Alzheimer's Disease Trial.

OBJECTIVE: To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer's disease (AD) who were treated with metrifonate during a randomized double blind clinical trial. DESIGN: Randomized clinical trial, with a 2-week screening period and a 26-week double blind, placebo controlled, treatment phase. Caregivers were assessed at baseline, at 12 weeks, and at end of trial. SETTING: Caregivers were interviewed at clinics as part of the assessment of the patients. PARTICIPANTS: Six hundred and three caregivers of AD patients who were enrolled in the MALT trial; 591 (98%) provided data suitable for analysis at baseline, and 546 (91%) provided data allowing for inclusion in the analysis of change scores. MEASUREMENTS: The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden, including both subjective (SCB-subj) and objective (SCB-obj) scores; the cognitive subscale of Poulshock and Deimling (PD); an abridged version of the Relatives Stress Scale (aRSS); assessments of time spent in providing care, including the Caregiver Activity Time Scale (CATS); and demographic and background variables on both the patient and caregiver. RESULTS: Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers, as measured by the SCB-subj, the PD, and the aRSS. There were no statistically significant differences on the measures assessing the time spent in caregiving, except for the caregiver's subjective impression of the change in time spent providing care during the trial. When comparing individual dose groups, most of the measures of burden showed the largest benefits in burden for the 60/80 mg group, followed by the 40/50 mg group, and then the placebo group. However, there was no statistically significant dose effect. CONCLUSIONS: This study provides the first evidence from a randomized clinical trial of any acetylcholinesterase inhibitor used in the treatment of AD demonstrating a positive impact on the patient's caregiver as well as benefits to the patient. These results were shown consistently across several measurement scales and were observed after six months of treatment. These findings reinforce the clinical significance of research that has shown that metrifonate has beneficial impacts on the cognitive, behavioral, and functional abilities of AD patients. Because caregiver burden is a leading factor in the decision for institutional care placement, the ability to favorably impact that burden through pharmacological treatment of the patient is important.

Aged↗
PubMed2000

Development of minimal lentivirus vectors derived from simian immunodeficiency virus (SIVmac251) and their use for gene transfer into human dendritic cells.

Lentivirus-derived vectors are very promising gene delivery systems since they are able to transduce nonproliferating differentiated cells, while murine leukemia virus-based vectors can only transduce cycling cells. Here we report the construction and characterization of highly efficient minimal vectors derived from simian immunodeficiency virus (SIVmac251). High-fidelity PCR amplification of DNA fragments was used to generate a minimal SIV vector formed from a 5' cytomegalovirus early promoter, the 5' viral sequences up to the 5' end of gag required for reverse transcription and packaging, the Rev-responsive element, a gene-expressing cassette, and the 3' long terminal repeat (LTR). Production of SIV vector particles was achieved by transfecting 293T cells with the vector DNA and helper constructs coding for the viral genes and the vesicular stomatitis virus glycoprotein G envelope. These SIV vectors were found to have transducing titers reaching 10(7) transducing units/ml on HeLa cells and to deliver a gene without transfer of helper functions to target cells. The central polypurine tract can be included in the minimal vector, resulting in a two- to threefold increase in the transduction titers on dividing or growth-arrested cells. Based on this minimal SIV vector, a sin vector was designed by deleting 151 nucleotides in the 3' LTR U3 region, and this SIV sin vector retained high transduction titers. Furthermore, the minimal SIV vector was efficient at transducing terminally differentiated human CD34(+) cell-derived or monocyte-derived dendritic cells (DCs). Results show that up to 40% of human primary DCs can be transduced by the SIV vectors. This opens a new perspective in the field of immunotherapy.

Cell Line↗
PubMed2000

Total hip arthroplasty with use of the Metasul metal-on-metal articulation. Four to seven-year results.

BACKGROUND: Total hip replacements with a metal-on-metal articulation were commonly used until the mid-1970s; most were then abandoned in favor of hip replacement with a metal-on-polyethylene articulation. The reason for this change was primarily early cup loosening, which was more prevalent with these metal-on-metal designs than it was with metal-on-polyethylene designs. In the late 1980s, a metal-on-metal design with improved clearance (adequate space between the femoral head and the acetabular articulation surface to allow fluid film lubrication and clearance of any debris from within this joint), metal hardness, and reproducible surfaces was introduced by Sulzer Orthopedics in Switzerland. Orthopaedic surgeons were interested in this Metasul articulation because the contribution of polyethylene wear particles to the failure of total hip replacements had become evident. This study was undertaken to review the clinical performance of this implant and to determine if early acetabular loosening or revision and wear and osteolysis were prevalent. METHODS: Between 1991 and 1994, seventy patients (seventy hips) had a total hip replacement with the Metasul metal-on-metal articulation and a cemented Weber cup. Nine patients died less than four years after the replacement; none of these deaths were related to the operation. Five patients were not available for radiographic evaluation, but they were contacted and it was known that the hip was not painful and had not been revised. Fifty-six patients (fifty-six hips) had complete clinical and radiographic data four to 6.8 years after the operation, and they made up the study group. The patients were evaluated with use of the Harris hip score, a patient-self-assessment form, and radiographs. RESULTS: At an average of 5.2 years (range, four to 6.8 years) after the operation, the average total Harris hip score for the fifty-three patients who did not have a revision was 89.6 points (range, 62 to 100 points). The average Harris pain score was 41.0 points (range, 30 to 44 points), and the average Harris limp score was 9.4 points (range, 5 to 11 points). One patient had revision of a loose cup, but there were no other loose acetabular components in the series. Two patients had revision of the acetabular component because of dislocation. No patient had a loose or revised femoral component. Therefore, the mechanical failure rate was one (2 percent) of fifty-six patients. Thirty-six of forty-seven patients who completed the patient-self-assessment form rated their result as excellent; seven, as very good; two, as good; one, as fair; and one, as poor. Wear could not be measured on radiographs because of the metal-on-metal articulation. No hip had radiographic evidence of acetabular osteolysis and two hips had calcar resorption, but there was no other radiographic evidence of focal osteolysis. CONCLUSIONS: Our four to seven-year experience with this articulation surface indicates that the clinical results are similar to those of total hip replacements with a metal-on-polyethylene articulation. We believe that the Metasul articulation may have a role in reducing the wear that occurs with total hip replacement. The Metasul articulation appears to be particularly indicated for more active patients. A historical comparison with the reports in the literature of which we are aware indicated that the hips in our study had a lower rate of acetabular revision and loosening than did those with previous metal-on-metal designs and that they had no more acetabular loosening or osteolysis than did those with metal-on-polyethylene articulations followed for an average of five years.

Adult↗
PubMed2000

Antibody responses to Plasmodium falciparum: evolution according to the severity of a prior clinical episode and association with subsequent reinfection.

We measured sporozoite- and total parasite antigen-specific IgG and IgM antibodies before and after treatment in matched groups of Gabonese children who presented with either mild or severe Plasmodium falciparum malaria. We investigated the influence of various parameters on these antibody responses, including clinical presentation, age, and post-treatment reinfection profiles. IgG but not IgM responses were strongly influenced by both clinical and parasitological status. IgG responses to the repeat region of the circumsporozoite protein, which were low at admission, particularly so in those with severe anemia, increased after treatment but showed no association with either age or reinfection profiles. Total parasite antigen-specific IgG responses were strongly influenced by parasitological status, and also differed significantly when segregated according to clinical status at admission, age, and reinfection histories. Most notably, anti-parasite IgG responses measured when children were parasite-free were higher and a good indicator of recent reinfections in those who presented with mild rather than with severe malaria. The profile of responses in the latter group suggests some immune system dysfunction, which may reflect the induction of tolerance to parasite antigens.

Animals↗