The group B streptococcal capsular carbohydrate: immune response and molecular mimicry.
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Biomedical subjects
Publications and source records attributed to S David.
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OBJECTIVES: The purpose of this study was to determine if early triage angiography with revascularization, if indicated, favorably affects clinical outcomes in patients with suspected acute myocardial infarction who are ineligible for thrombolysis. BACKGROUND: The majority of patients with acute myocardial infarction and other acute coronary syndromes are considered ineligible for thrombolysis and therefore are not afforded the opportunity for early reperfusion. METHODS: This multicenter, prospective, randomized trial evaluated in a controlled fashion the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with <24 h of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy consisting of aspirin, intravenous heparin, nitroglycerin, beta-blockers, and analgesics. RESULTS: In the triage angiography group, 109 patients underwent early angiography and 64 (58%) received revascularization, whereas in the conservative group, 54 (60%) subsequently underwent nonprotocol angiography in response to recurrent ischemia and 33 (37%) received revascularization (p=0.004). The mean time to revascularization was 27+/-32 versus 88+/-98 h (p=0.0001) and the primary endpoint of recurrent ischemic events or death occurred in 14 (13%) versus 31 (34%) of the triage angiography and conservative groups, respectively (45% risk reduction, 95% CI 27-59%, p=0.0002). There were no differences between the groups with respect to initial hospital costs or length of stay. Long-term follow-up at a median of 21 months revealed no significant differences in the endpoints of late revascularization, recurrent myocardial infarction, or all-cause mortality. CONCLUSIONS: Early triage angiography in patients with acute coronary syndromes who are not eligible for thrombolytics reduced the composite of recurrent ischemic events or death and shortened the time to definitive revascularization during the index hospitalization. Despite more frequent early revascularization after triage angiography, we found no long-term benefit in cardiac outcomes compared with conservative medical therapy with revascularization prompted by recurrent ischemia.
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STUDY OBJECTIVE: Concordant results have been reported in several studies for the effects of job stress on cardiovascular disease, but the potential mechanisms of these effects have seldom been explored. The aim of this study was therefore to examine, in women and men, the cross sectional relations between psychosocial work variables (psychological demands, decision latitude, and social support) and cardiovascular risk factors (hypertension, hyperlipidaemia, diabetes, overweight, smoking, and alcohol consumption). PARTICIPANTS: The original cohort comprised 20,625 volunteers (men aged from 40 to 50 and women from 35 to 50) employed by the French Company Electricité De France-Gaz De France and followed up yearly since 1989. The study was restricted to the 13,226 volunteers in the cohort who were still working and answered a self administered questionnaire on psychosocial work factors in 1995. DESIGN: Data were based on replies to this questionnaire. Three psychosocial work environment exposure scores were used to assess psychological demands, decision latitude, and social support at work respectively. The main outcome measures were the prevalence of hypertension, hyperlipidaemia, and diabetes within the previous 12 months, overweight, smoking, and alcohol consumption. MAIN RESULTS: Psychosocial work factors were significantly associated with hypertension, hyperlipidaemia, overweight, smoking, and alcohol consumption, but not with diabetes. In men, low decision latitude was associated with hypertension, high decision latitude and high social support with overweight, low decision latitude with alcohol consumption. Moreover, the risk of hyperlipidaemia increased in men exposed to both high psychological demands and low social support. In women, low decision latitude was related to hyperlipidaemia, high psychological demands with overweight, high psychological demands and high decision latitude with smoking, and low social support with alcohol consumption. CONCLUSIONS: These cross sectional results underline the potential effects of psychosocial work characteristics on cardiovascular risk factors and the differences between the effects of job stress in men and women, and confirm the direct mechanisms (through physiological variables) and indirect mechanisms (through behavioural risk factors) potentially involved in the relation between psychosocial work characteristics and cardiovascular disease.
A central role for the Schwann cell cytoskeleton in the process of peripheral nerve myelination has long been suggested. However, there is no genetic or biological evidence as yet to support this assumption. Here we show that dystonia musculorum (dt) mice, which carry mutations in dystonin, a cytoskeletal crosslinker protein, have hypo/amyelinated peripheral nerves. In neonatal dt mice, Schwann cells were arrested at the promyelinating stage and had multiple myelinating lips. Nerve graft experiments and primary cultures of Schwann cells demonstrated that the myelination abnormality in dt mice was autonomous to Schwann cells. In culture, dt Schwann cells showed abnormal polarization and matrix attachment, and had a disorganized cytoskeleton. Finally, we show that the dt mutation was semi-dominant, heterozygous animals presenting hypo- and hyper-myelinated peripheral nerves. Altogether, our results suggest that dt Schwann cells are deficient for basement membrane interaction and demonstrate that dystonin is an essential component of the Schwann cell cytoskeleton at the time of myelination.
OBJECTIVE: This study attempted to establish whether psychosocial factors at work are predictors of depressive symptoms in a prospective cohort of men and women employed in a wide variety of occupations by the French national company Electricité De France - Gaz De France (EDF-GDF). METHODS: This prospective cohort study followed the Gazel cohort by means of annual self-administered questionnaires and independent data obtained from the medical and personnel departments of the company. The self-administered questionnaire, in 1995, provided information about the psychosocial work environment characteristics, psychological job demands, decision latitude, and social support at work. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) Scale in the 1996 questionnaire. Potential confounding variables were age, marital status, and number of children, assessed in the 1995 questionnaire, stressful personal and occupational events during the previous 12 months, assessed in the 1996 questionnaire, and educational level, occupation and previous absenteeism for mental disorders, assessed from the independent data provided by EDF-GDF. The subjects were 11 552 workers (8422 men aged 46-56 years in 1995 and 3130 women aged 41-56 years) who answered the 1995 and 1996 questionnaires and were working during this period. RESULTS: High levels of psychological demands, low levels of decision latitude, and low levels of social support at work were significant predictors of subsequent depressive symptoms in both the men and the women. These results were unchanged after adjustment for potential confounding variables. CONCLUSIONS: The results strongly support the possibility that psychosocial factors at work are predictive of depressive symptoms.
Ultrasonography has been shown to be valuable in diagnosis of appendicitis in children. For the management of cases where clinical and ultrasonography findings lead to different results, we evaluated standard therapeutical concepts which have been proved to be reliable in our clinic.
OBJECTIVE: There is a known relationship between blood glucose control and development or progression of complications in diabetes mellitus. The aim of our study was to assess the quality of hospital care in patients with insulin-dependent diabetes. PATIENTS AND METHODS: A prospective study was conducted over a 6-month period (April 95-September 95) to perform a clinical audit comparing results obtained with care standards. The study group included 257 consecutive patients (age range 15-39 years) who consulted the hospital outpatient clinic of were hospitalized for insulin-dependent diabetes mellitus RESULTS: Results differed depending on the care standards used for comparison. There were 45 patients (17%) who consulted 4 times or more; 43% of the patients were not hospitalized and 32% did not had a fundus examination during the preceding year. There was a 51% deviation from the standard number of capillary blood glucose measurements and 72% of the patients stated they adapted their insulin dose. Mean glycosylated hemoglobin level (HPLC method) was 9.78 +/- 2.37% (standard = 7%). CONCLUSION: This assessment of hospital care demonstrated a deviation of medical surveillance from standard care. More frequent consultations would help improve patient information. It is important to recall that an annual hospitalization and rigorous application of clinical surveillance with annual fundus examination are essential. Information provided by physicians, nurses and dietitians should be an integral part of hospital care. Likewise, it is undoubtedly useful to provide psychological counselling for diabetic patients. A reassessment should evaluate the impact of such recommendations in order to determine the impact, in terms of reduced mortality, of improved hospital care.
Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in plasma of hepatic origin. We now provide evidence for a novel membrane-bound form of ceruloplasmin expressed by astrocytes in the mammalian central nervous system. Using a monoclonal antibody (1A1), we show that the cell surface antigen recognized by this antibody is ceruloplasmin and that it is directly anchored to the cell surface via a glycosylphosphatidylinositol (GPI) anchor. Our peptide mapping and other immunochemical studies indicate that, except for the GPI anchor, the membrane-bound and secreted plasma forms are similar. We also show that the membrane-bound form of ceruloplasmin has oxidase activity. These studies therefore suggest that the GPI-anchored form of ceruloplasmin may play a role similar to the secreted form in oxidizing ferrous iron. The GPI-anchored form of ceruloplasmin expressed by astrocytes is likely to be the major form of this molecule in the central nervous system because serum ceruloplasmin does not cross the blood-brain barrier. Lack of this form of ceruloplasmin in the central nervous system could lead to the generation of highly toxic free radicals, which can cause neuronal degeneration as seen in aceruloplasminemia and other neurodegenerative diseases such as Parkinson's and Alzheimer's disease.
Axon growth-promoting and -inhibitory molecules are likely to work in concert to promote and guide axons in vivo. In adult mammals, inhibitory molecules associated with myelin in the white matter of the central nervous system (CNS) play an important role in the failure of long-distance axon regeneration. The presence of neurite growth-inhibitory molecules in the adult rat gray matter has not been extensively studied. In this article we describe work on the characterization of neurite growth-inhibitory activity in the adult rat cerebral cortical gray matter using various biochemical and cell culture approaches. We show using a neuronal cell line (NG108-15 cells) that neurite growth-inhibitory activity is present in membrane preparations of the cortical gray matter. Purified gray matter membranes also induce growth cone collapse of cultured embryonic rat dorsal root ganglion neurons. The inhibitory activity in the membrane preparations is extractable with 3-[(3-cholamidoprophyl)-dimethylammonio]-1-propane-sulfonate, but does not appear to be depleted by various lectins. Western blots and enzyme treatments showed that the inhibitory effect of the gray-matter preparations is not likely to be mediated by myelin-associated inhibitors or chondroitin sulfate proteoglycans. However, tenascin was detected in these samples and may contribute to some of the inhibitory activity. Selective separation of the inhibitory molecules can be achieved by ion-exchange chromatography, which also suggests the presence of multiple inhibitors in cortical gray matter membranes.
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Leptomeningeal cells migrate into the lesion cavity after stab wounds to the adult mammalian central nervous system (CNS) and interact with astrocytes that form a new glia limitans. However, it is not known if leptomeningeal cells alter the ability of astrocytes near the lesion to support axon growth. In this study, we have used an in vitro approach to assess leptomeningeal cell-astrocyte interactions in a model that resembles the interactions of these cells in vivo. We cultured rat cortical astrocytes on top of monolayers of leptomeningeal cells or astrocytes. Differences in the morphology, neurite growth promoting properties, and expression of various extracellular matrix molecules and beta 1-integrin were assessed. Astrocytes acquired a long slender morphology when plated on leptomeningeal cells. Functionally, astrocytes cultured on top of leptomeningeal monolayers supported less neurite growth. Similar results were also obtained when astrocyte monolayers were treated with leptomeningeal cell-conditioned medium. Quantitative immunofluorescence labeling showed a reduction in cell surface bound laminin on astrocytes plated on leptomeningeal monolayers. Qualitative assessment of the immunofluorescence labeling showed an increase in matrix-like deposits of tenascin-C and chondroitin sulfate proteoglycan under similar culture conditions. This study provides the first direct evidence that leptomeningeal cells reduce the neurite growth promoting properties of astrocytes. These results suggest that interactions with leptomeningeal cells may 1) induce the formation of the slender astrocyte processes that form parallel to the lesion wall after penetrating injuries to the CNS; and 2) contribute along with other factors to alter astrocytes near the site of injury to a state that is less permissive for axon growth and regeneration.
We have examined the regeneration of corticospinal tract fibers and expression of various extracellular matrix (ECM) molecules and intermediate filaments [vimentin and glial fibrillary acidic protein (GFAP)] after dorsal hemisection of the spinal cord of adult GFAP-null and wild-type littermate control mice. The expression of these molecules was also examined in the uninjured spinal cord. There was no increase in axon sprouting or long distance regeneration in GFAP-/- mice compared to the wild type. In the uninjured spinal cord (i) GFAP was expressed in the wild type but not the mutant mice, while vimentin was expressed in astrocytes in the white matter of both types of mice; (ii) laminin and fibronectin immunoreactivity was localized to blood vessels and meninges; (iii) tenascin and chondroitin sulfate proteoglycan (CSPG) labeling was detected in astrocytes and the nodes of Ranvier in the white matter; and (iv) in addition, CSPG labeling which was generally less intense in the gray matter of mutant mice. Ten days after hemisection there was a large increase in vimentin+ cells at the lesion site in both groups of mice. These include astrocytes as well as meningeal cells that migrate into the wound. The center of these lesions was filled by laminin+/fibronectin+ cells. Discrete strands of tenascin-like immunoreactivity were seen in the core of the lesion and lining its walls. Marked increases in CSPG labeling was observed in the CNS parenchyma on either side of the lesion. These results indicate that the absence of GFAP in reactive astrocytes does not alter axonal sprouting or regeneration. In addition, except for CSPG, the expression of various ECM molecules appears unaltered in GFAP-/- mice.
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The orientation of elderly patients, temporarily disabled, to acute care beds is inappropriate because of its adverse effects on functional status and its costs. The creation of short-stay units (SSU) in nursing homes provides an alternative to acute care hospitalization. The aim of this retrospective study, involving the first 64 patients oriented to the SSU from the emergency center, was to evaluate this new health care network. The analysis was focused on the rate of appropriate orientation (site of living at four month; subsequent medical events), as well as the functional quality of this health care network. Information were collected from medical records of the 64 patients oriented to SSU and 64 sex- and age-matched patients admitted during the same period, and the opinion of the network's partners. The mean age of patients and controls was 82 years. Four months after admission to the SSU, the orientation was considered appropriate in 58% of the cases (living at home without subsequent hospitalization), doubtful in 8%, and inappropriate in 33%; 27% of patients and 13% of controls were living definitely in nursing homes (p < 0.1). No medical or social characteristics was correlated to inappropriate orientations. In conclusion, the creation of SSU may be considered as an improvement in the care of elderly patients. The main problem of this orientation was the high percentage of patients living permanently in a nursing home four months later. Accurate assessment's tools capable to predict the subsequent decrease of the functional status should be used in the daily practice in order to improve the orientation of elderly patients.
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Spontaneous spinal epidural hematoma is an uncommon clinical entity. Patients with this disease may present with devastating neurological deficits that can mimic other diseases. Emergency physicians should be familiar with this condition to assure appropriate therapy in a timely manner. A typical case of spontaneous spinal epidural hematoma is presented with review of appropriate differential diagnosis and management.
The CD34 antigen is present at all differentiation stages of hematopoietic cells, from immature progenitor cells to committed precursor cells. In vivo, transplantation of CD34+ cells is sufficient to allow hematopoietic recovery after myeloablative chemotherapy, but a neutropenic period of 9-12 days still exists, even when hematopoietic growth factors are given posttransplantation. After ex vivo expansion cultures in the presence of cytokines, CD34+ cells can generate mature precursor cells in a stroma-free liquid culture system. This could lead to a shortening of the aplasia duration, but the persistence of primitive progenitor cells in the expanded CD34+ compartment remains to be demonstrated. In this study, CD34+ cells were isolated from eight peripheral blood (PB) and eight cord blood (CB) samples using either Isolex 50 (n = 6), Ceprate LC CD34 kit (n = 6), or Microcellector T-25 Stem Cell kit (n = 4). We have evaluated the functional potential of CD34+ cells after 7 days of ex vivo expansion culture in the presence of 500 UI/ml of interleukin-1 (IL-1), 10 ng/ml of IL-3, and 10 ng/ml of stem cell factor (SCF). The expansions of nucleated cells, granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive committed precursors, IL-1 + IL-3 + SCF + erythropoietin (EPO)-responsive multilineage progenitors, and 5-fluorouracil (5-FU)-resistant quiescent progenitor were 8-fold, 59-fold, 4.4-fold, and 2.2-fold, respectively. There was no significant difference in the amplification/expansion parameters between cultures initiated with CD34+ cells from PBSC or CB. Our data confirm that cytokine-mediated ex vivo expansion of blood CD34+ cells can produce large numbers of committed precursors and does not significantly affect the compartment containing more immature progenitors. Cytokine-mediated expansion could be of great interest in autologous transplantation to decrease the duration of marrow aplasia.