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Biomedical subjects

B Lucas

Publications and source records attributed to B Lucas.

At least 55 records · Page 3Linked to original sources

[Contribution of magnetic resonance imaging in sclerotic combined degeneration of the spinal cord due to vitamin B12 deficiency].

Subacute combined degeneration (SCD) of the spinal cord is known to present histopathologically degenerative lesions in the spinal cord, but few studies on the neuroradiological findings have so far been reported. We present the interest of initial and follow-up MR findings in three cases of SCD. In the three cases, a causal event precipitated the onset of neurological symptoms: general anesthesia for the first and the third one and folic acid treatment for the second one. Clinical evolution was favorable after specific treatment with nearly total recovery. The initial MR study disclosed lesions predominantly involving the posterior columns of the spinal cord: high intensity on T2 weighted image was seen in the initial MR study and disappeared three months after treatment in correlation with good recovery, but with a delay. The recognition of this MR pattern suggests that MRI may be used in conjunction with clinical assessment to confirm the diagnosis and to monitor the efficacity of treatment in SCD.

Aged↗

Timing and casting for actors of thymic negative selection.

We have recently proposed a new model for the differentiation pathway of alphabeta TCR thymocytes, with the CD4 and CD8 coreceptors undergoing an unexpectedly complex series of expression changes. Taking into account this new insight, we reinvestigated the timing of thymic negative selection. We found that, although endogenous superantigen-driven thymic negative selection could occur at different steps during double-positive/single-positive cell transition, this event was never observed among CD4lowCD8low TCRint CD69+ thymocytes, i.e., within the first subset to be generated upon TCR-mediated activation of immature double-positive cells. We confirm a role for CD40/CD40L interaction, and the absence of involvement of CD28 costimulation, in thymic deletion in vivo. Surprisingly, we found that thymic negative selection was impaired in the absence of Fas, but not FasL, molecule expression. Finally, we show involvement in opposing directions for p59fyn and SHP-1 molecules in signaling for thymic negative selection.

Animals↗

Nanoindentation studies of titanium single crystals.

Titanium single crystal planes of different atomic density have been reported to show different oxidation characteristics. The differences in oxide characteristics have further been demonstrated to lead to differences in osteoblast attachment. Investigations of the preferred crystallographic planes of titanium for osteoblast attachment can be used to optimize the surfaces of single crystal and polycrystalline titanium implants for anchoring various prostheses. Nanoindentation techniques were used to determine mechanical properties of two crystallographic planes of titanium of different atomic density. Modulus of elasticity of 128 +/- 10 GPa was obtained for polycrystalline titanium and 123 +/- 5 and 124 +/- 6 GPa for the basal plane and pyramidal planes, respectively. The variation of modulus with crystal orientation was not greater than the statistical variation in the data. Surface hardness values were 2.1 +/- 0.1 GPa for the polycrystalline sample and 1.6 +/- 0.1 and 1.9 +/- 0.1 GPa, respectively, for the basal and pyramidal planes. Curves of hardness as a function of depth (0-2000 nm) obtained from electrochemically polished surfaces showed a sharp increase at shallow depths and may reflect changes caused by oxidation of the titanium surfaces.

Biocompatible Materials↗

Divergent changes in the sensitivity of maturing T cells to structurally related ligands underlies formation of a useful T cell repertoire.

CD4+ CD8+ thymocyte differentiation requires TCR signaling induced by self-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we show that the signaling properties of TCR change during thymocyte maturation, differentially affecting responses to related peptide/MHC molecule complexes and contributing to this discrimination. Weak agonists for CD4+ CD8+ thymocytes lose potency during development, accompanied by a change in TCR-associated phosphorylation from an agonist to a partial agonist/antagonist pattern. In contrast, sensitivity to strong agonists is maintained, along with full signaling. This yields a mature T cell pool highly responsive to foreign antigen while possessing a wide margin of safety against activation by self-ligands.

Amino Acid Sequence↗

Sleep and epilepsy.

This review considers the effect of sleep on seizures and interictal electroencephalogram (EEG) paroxysmal activities (PAs), as classified by the International League Against Epilepsy criteria. No type of seizure is, per se, specifically linked with non-rapid eye movement (NREM) or rapid eye movement (REM) sleep. However, in some syndromes, seizures are more frequent in slow wave sleep (SWS) [partial motor or generalized seizure in benign epilepsy with centro-temporal spikes (BECTS), frontal seizures in idiopathic familial or not familial frontal lobe epilepsy and generalized tonic seizure in secondary generalized epilepsy are increased by SWS]. Conversely myoclonia and grand mal seizures are associated with awakening in some forms of generalized idiopathic epilepsy. There is a mean increase in PAs during SWS in generalized and in partial epilepsies on the whole. However, precise analysis shows that in partial cryptogenic or symptomatic epilepsy and, most likely, in the majority of generalized idiopathic epileptic syndromes about 20% of patients have an increase in PA density during SWS, 20% experience an increase in waking, 50% have very few PAs and in 10% there is no significant difference between sleep and waking. BECTS, however, exhibits a definite increase in sleep PA increase and in juvenile myoclonic epilepsy an increase in PAs during the intra-night awakening is reported. There are at least three syndromes, which cause a huge increase in PAs during sleep: the Landau-Kleffner syndrome and the syndromes of continuous focal or generalized spike-waves during SWS. Their physiopathology and neuropsychological consequences are discussed. Neurophysiological animal data are also reported highlighting the relationships between slow sleep oscillations and the generation of spike waves. A biochemical review is also presented.

Journal Article↗

[Fotemustine (Muphoran) in 22 patients with relapses of high-grade cerebral gliomas].

Fotemustine is a third-generation nitrosourea characterized by a phosphoalanine carrier group grafted onto the nitrosourea radical, which gives it a high lipophilicity and a better penetration through the cell membrane. Between September 1988 and December 1997, 22 patients with inoperable or incompletely resected recurrent high-grade gliomas of the brain were treated at the University Hospital in Brest (France). Treatment consisted of three weekly infusions of fotemustine (100 mg/m2 days 1, 8 and 15). If patients responded or were stabilized, fotemustine was continued at the same dose, but every three weeks only. Four patients responded to the treatment (18%), while 6 were stabilized (32%). Main toxicity was haematologic (leucopenia and, above all, thrombocytopenia); treatment was only interrupted in one patient for leucothrombopenia, and there was no toxic death. Medium duration of response and/or stabilisation was 6.5 months, and median survival 9.4 months in responding and/or stabilized patients, while it was only 5.0 months if tumour progressed under chemotherapy (median survival for all patients: 7.5 months). Besides, there was a difference in survival in favour of the young patients (< 50 years-median survival = 11.8 months) in comparison with patients between 50 and 60 years (median survival = 6.8 months; p = 0.0282) or elderly patients (> 60 years-median survival = 5.8 months; p = 0.0634). In our series, we did not found any difference in survival according to the initial performance status of patients before treatment. Therefore, fotemustine seems to represent an interesting well-tolerated treatment possibility in patients with inoperable recurrent malignant gliomas of the brain.

Antineoplastic Agents↗

Does a hostel's managing agency determine the access to psychiatric services of its residents?

This study examines the effect of managing agency (local authority, private or voluntary) on the use of other health and social care services by residents in mental health hostels and group homes with different levels of staffing in England and Wales. The sample comprised 1323 residents in 275 facilities in eight districts. The measures of service use were number of days in hospital and number of other service contacts. There were highly significant differences between facilities with similar levels of staffing managed by different agencies. Residents in the voluntary sector used fewer community services overall; residents in low-staffed local authority facilities used more services than those in similar facilities managed by other agencies. These differences were not easily explained by differences in the social or clinical characteristics of residents. This suggests that there may be organisational factors, e.g. hostel staff, knowledge of services, which influence access to and use of community services.

Adult↗

Protection of mice against gastric colonization by Helicobacter pylori by single oral dose immunization with attenuated Salmonella typhimurium producing urease subunits A and B.

Helicobacter pylori is a Gram-negative bacterial pathogen associated with gastritis, peptic ulceration, and gastric carcinoma. The bacteria express a strong urease activity which is known to be essential for colonization of gnotobiotic pigs and nude mice. UreA and UreB, two structural subunits of the active enzyme, were expressed in the attenuated Salmonella typhimurium live vaccine SL3261 strain. Evaluation of protection against H. pylori was performed in Balb/c mice by oral immunization with a single dose of the vaccine strain. Five weeks after immunization, mice were challenged orally three times with a mouse-adapted H. pylori wild type strain and, six weeks later, mice were sacrificed to determine H. pylori infection by detection of urease activity from the antral region of the mouse stomachs. In several independent experiments, we observed 100% infection with H. pylori in the non-immunized mice and no infection (100% protection) in the mice immunized with S. typhimurium expressing recombinant UreA and UreB. Specific humoral and mucosal antibody responses against UreA and UreB were observed in mice immunized as indicated by western blots and ELISA assays. These data shows that oral immunization of mice with urease subunits delivered by an attenuated Salmonella strain induced a specific immune response and protected mice against H. pylori colonization. Single oral dose immunization with UreA and UreB delivered by a live Salmonella vaccine vector appears to be an attractive candidate for human vaccination against H. pylori infection. In addition, this model will aid to elucidate the effective protection mechanisms against H. pylori in the gastric mucosa.

Administration, Oral↗

[Emergency EEG and brain injuries].

The aim of this study is to review indications for emergency EEG in case of brain trauma. The authors emphasize the indication of emergency EEG for the diagnosis of either cerebral death or early post traumatic seizures, and for the monitoring of intensive neurological treatments. Emergency EEG and diagnosis of cerebral death has been reviewed in another issue of this journal. Diagnosis of early post-traumatic seizures may be difficult in case of cranial trauma in either the presence or the absence of coma. Emergency EEG help guide the diagnosis of electrical signs of seizures, thus indicating that treatment with antiepileptic drugs is advisable. Severe post-traumatic coma requires barbiturate impregnation and moderate hypothermia. In this last case, emergency EEG is essential for the monitoring of pharmacological treatments. The authors conclude that continuous EEG monitoring could in the future substitute for standard EEG recorded in emergency.

Brain Death↗

A molecular map of T cell development.

Using a sensitive molecular marker for positive selection, the appearance of a particular functional TCR alpha chain sequence in cells from mice bearing a transgenic beta chain, we address several aspects of intrathymic T cell development. First, by examining specific TCR prior to and after maturation, we demonstrate how a restricted TCR repertoire is positively selected from a highly diverse immature TCR repertoire. Second, since this molecular marker is enriched in cells progressing toward the CD4 lineage and depleted in cells progressing toward the CD8 lineage, a map of the developmental pathway of alphabeta thymocytes can be inferred. Third, the first cells that show clear signs of positive intrathymic selection are identified.

Amino Acid Sequence↗

Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.

Mice carrying a germ-line null mutation of the prolactin receptor gene have been produced by gene targeting in embryonic stem cells. Heterozygous females showed almost complete failure of lactation attributable to greatly reduced mammary gland development after their first, but not subsequent, pregnancies. Homozygous females were sterile owing to a complete failure of embryonic implantation. Moreover, they presented multiple reproductive abnormalities, including irregular cycles, reduced fertilization rates, defective preimplantation embryonic development, and lack of pseudopregnancy. Half of the homozygous males were infertile or showed reduced fertility. This work establishes the prolactin receptor as a key regulator of mammalian reproduction, and provides the first total ablation model to further study the role of the prolactin receptor and its ligands.

Animals↗

Sleep and the epilepsies.

To review the numerous works concerning sleep and epilepsy, this review considers the effects of sleep, firstly on seizures and secondly on paroxysmal interictal EEG activity (PA), in the different types of epilepsy according to the International League against Epilepsy classification. Apart from the exceptions of the definite nocturnal preponderance of seizures in idiopathic rolandic epilepsy and of the mostly nocturnal occurrence of seizures in some types of familial or sporadic frontal-lobe epilepsy, assessing a seizure according to the time of day it occurs is of no diagnostic or predictive value. In generalised idiopathic epilepsy, as in partial symptomatic or cryptogenic epilepsy, only about 20% of the patients had a sleep increase in PA. This percentage is higher (75%) in idiopathic partial epilepsy. Stereoelectroencephalography demonstrates a relative stability of spiking within the focus across the states of vigilance and an increase in transmitted discharges during stages 3 and 4. In the Landau and Kleffner syndrome, as in the syndromes of continuous spike-waves during sleep, there is a huge, unexplained increase in PA during sleep. The neuropsychological consequences of this PA have some relationship with their localisation and the patient's age at the time of occurrence. Sleep PA has also been reported in several groups of non-epileptic subjects. As regards the effect of epilepsy on sleep, sleep may be lighter and abnormally discontinuous in the absence of seizures, particularly in temporal-lobe epilepsy.

Epilepsy↗

Linking health plan performance with disability outcomes.

Although the managed health care industry evolved and matured in the 1980s and 1990s, such initiatives to control disability costs failed to keep pace. As employers became aware of the costs of lost productivity, managed disability programs quickly evolved. This article discusses the trends, issues and assumptions in managed health and disability models, providing case studies to support the authors' hypothesis that health plans can have a direct impact on disability duration.

Absenteeism↗

[Split-course concomitant radiochemotherapy plus surgery vs. surgery alone in squamous cell carcinoma of the esophagus. A non-randomized retrospective study of 184 patients].

From April 1989 to October 1995, 184 patients with squamous cell carcinomas of the esophagus were treated either with surgery alone (112 patients) or with preoperative concomitant radiochemotherapy (72 patients) (2 courses of 18.5 Gy in 5 fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) days 1-5 and cisplatinum day 2, separated by a 2-week interval) followed by surgery, and by 4 more courses of chemotherapy alone for good responders. Twenty-seven of these last 72 patients showed histological complete response at surgery (37.5%). There was no statistically significant difference in overall survival between the 2 groups although there were much more T1 patients (small tumors < or = 5 cm in the previous TNM classifications) and less T3 patients (evidence of spread beyond the esophagus) in the surgery alone group, and nevertheless, median survival was better in the combined treatment group (33.6 months versus 21.8 months). However, considering tumor size, there was a statistically significant difference in median survival in favor of the combined treatment group for all T2 patients (> 5 cm without evidence of spread beyond the esophagus in the previous TNM classification) (48.6 months versus 13.8 months), both for T2N0 and T2N1 patients, but also for T1N1 patients (< or = 5 cm with nodal involvement). For the few T3 patients (evidence of spread beyond the esophagus in the previous TNM classification), there was no statistically significant difference between the 2 groups, but the survival curves seemed to show some advantage in favor of the combined treatment group for T3N1 patients. The sex of the patients and the third of the esophagus involved by the tumor did not seem to be of any influence on survival. On the other hand, patients 70-year-old and older showed a poorer survival than other patients. Finally, significantly less patients died with loco-regional recurrences in the preoperatory radiochemotherapy group (32% versus 48%) than in the group treated by surgery alone.

Adult↗

In vivo T cell response to viral superantigen. Selective migration rather than proliferation.

Superantigens induce T cell activation and proliferation in vitro, and some also induce cell activation in vivo. MMTV(SW) is an infectious mouse mammary tumor virus (MMTV) encoding a superantigen with the same Vbeta specificity as MIs-1a (Mtv-7), which induces a strong local response in vivo. injection of MMTV(SW) into mouse footpads leads to accumulation of superantigen-reactive T cells (Vbeta6+CD4+) and B cells in the draining lymph nodes (LN). We investigated the kinetics of this cell accumulation by measuring cell activation (blastogenesis, CD25 and CD69 expression), cell migration (using syngenic FITC-labeled CD4+ cells and L-selectin detection), and cell proliferation (using in vivo labeling with bromodeoxyuridine). Specific T cells selectively migrated to the draining LN. Accumulating Vbeta6+CD4+ T cells were large CD69+ cells, but remained CD25 negative and showed down-regulated L-selectin expression. Their DNA synthesis rate, studied by pulse labeling and continuous administration of bromodeoxyuridine, was increased, but remained too low to explain the draining LN hyperplasia. These data show that the local T cell response to MMTV(SW) mainly consists of selective migration followed by local activation of reactive T cells, and that cell proliferation is only a minor component of the response. By contrast, the optimal dose of staphylococcal enterotoxin B that, nevertheless, leads to a lower reactive T cell accumulation in the draining LN induces a very high proliferation rate.

Animals↗