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B Lucas

Publications and source records attributed to B Lucas.

At least 73 records · Page 4Linked to original sources
PubMed1996

CD4low TCRint thymocytes do not belong to the CD8 lineage maturation pathway.

Thymocytes with a low expression of CD4 and an intermediate density of the TCR (CD4low TCRint) were analyzed for phenotype, MHC dependence, production kinetics, and TCR repertoire to investigate their position in the intrathymic T cell maturation process. Comparison of normal and MHC-deficient mice showed that the CD4low TCRint cell subset was MHC class II dependent, as this subpopulation could not be defined in MHC class II- or double (class I and II)-deficient mice. These thymocytes were heat-stable Aghigh and CD69+, thus immature and recently engaged in a TCR interaction, probably with MHC class II molecules. Their generation kinetics were studied in two systems: development of exogenous bone marrow cells transferred into RAG-2-/- mice, and pulse labeling with bromodeoxyuridine. In both systems, CD4low TCRint cells were produced well before CD4low TCRhigh cells, the direct precursors of CD8 single-positive cells. Their production paralleled that of CD4high TCRint cells, but they were different than these thymocytes in their smaller cell size. Moreover, they had the same V beta 6 frequency in Mls-1a and Mls-1b mice, suggesting that these cells could be undergoing a negative selection process. The data here clearly demonstrate that CD4low TCRint thymocytes do not belong to the CD8 lineage maturation pathway, and suggest that these cells could represent a MHC class II-restricted dead-end subset.

Animals↗
PubMed1996

Preoperative concomitant radiochemotherapy in squamous cell carcinoma of the esophagus: results of a study of 56 patients.

PURPOSE: Today the prognosis for patients with esophageal carcinoma still remains quite poor. In the last few years interesting results have been obtained by associating radio- and chemotherapy with or without surgery with this type of cancer. In this work we report the results of concomitant radio- and chemotherapy in a split-course schedule preceeding surgery for the treatment of squamous cell carcinomas of the esophagus. METHODS AND MATERIALS: Fifty-six patients with squamous cell carcinomas of the esophagus were treated between April 1989 and September 1993 in the Centre Hospitalier Universitaire in Brest, France with two courses of preoperative concomitant radiochemotherapy, separated by a 2-week interval, and followed by surgery (each course 18.5 Gy in five fractions, days 1-5 with continuous infusion 5-fluorouracil (5-FU) 800 mg/m2 days 1-5 and cisplatinum 70 mg/m2 day 2). Patients who had responded well to preoperative treatment (response > 50%) received four more courses of chemotherapy alone. The two patients who were not operated and those with palliative surgery received a third course of radiochemotherapy (radiotherapy 12 Gy in five fractions, days 1-5). RESULTS: Fifty-four patients were operated on. Twenty-one showed histological complete response at surgery (37.5% of the whole group). Actuarial survival for the 56 patients was 55% at 3 years and 30% at 4 years, with a median survival of 37.4 months (40.4 months for complete responders to preoperative treatment). Toxicity of preoperative concomitant radio-chemotherapy was low (5-FU had to be stopped in one patient because of cardiac rythm disturbances and in another patient because of aplasia Grade 4 associated with infection after the first course). Postoperative mortality was 11% (six patients). CONCLUSION: This combination of preoperative radiochemotherapy followed by surgery seems to improve both response rates and survival in patients with esophageal cancer when compared with previous patients treated with surgery alone in our hospital or with results found in literature and it warrants further studies.

Aged↗
PubMed1996

Unexpectedly complex regulation of CD4/CD8 coreceptor expression supports a revised model for CD4+CD8+ thymocyte differentiation.

CD4+ CD8+ TCRlo thymocytes are the precursors of CD4+ and CD8+ mature T cells, whose receptors show specific recognition of peptide-MHC class II and MHC class I complexes, respectively. How T cells emerge from the intrathymic differentiation process with selective expression of either CD8 molecule or CD4 molecule coordinated with the MHC class specificity of the TCR has been the subject of intense examination. Many previous studies of this question have been based on the assumption that extinction of CD4 or CD8 expression by the precursor thymocytes was a steady, uninterrupted process. Here we show that this is an incorrect assumption, with CD4 and CD8 expression undergoing an unexpectedly complex series of expression changes involving down-modulation, kinetically asymmetric up-regulation, and then selective loss. Based on these data, we propose a model for the differentiation pathway of alphabeta TCR thymocytes that explains previous, apparently contradictory findings and establishes useful parameters for future studies at the cellular and gene level.

Animals↗
PubMed1996

Thymic medulla epithelial cells acquire specific markers by post-mitotic maturation.

The development of thymocyte subsets and of the thymic epithelium in SCID and RAG-2/-mice was monitored after normal bone-marrow-cell transfer. The kinetics of thymic reconstitution and their relationships with cell proliferation were investigated by using bromodeoxyuridine to detect DNA-synthesizing cells among lymphoid cells by 3-color flow cytometry, and in epithelial compartments by staining frozen sections. Thymocytes started to express CD8 and CD4 10 days after transfer, simultaneously with extensive proliferation. The first mature CD4+ single-positive cells were generated, from resting CD4+CD8+ cells after day 15. During this day 10-15 period, many epithelial cells positive for cortex-specific or panepithelial markers were labeled with BrdUrd after pulse-injection. Organized medullary epithelium also developed after day 15, that is, synchronously with the appearance of mature thymocytes, but medullary cells were never found BrdUrd+. These results suggest that, in these models, the reconstitution of the thymic epithelial network proceeds through expansion of preexisting cortical or undifferentiated cells and by later maturation (acquisition of specific markers) of medullary cells. This last process is dependent of the presence of mature thymocytes.

Animals↗
PubMed1996

In vivo treatment with interleukin 2 reduces parasitemia and restores IFN-gamma gene expression and T-cell proliferation during acute murine malaria.

In this study, we describe the functional alterations in the host immune system that occur following acute infection with Plasmodium yoelii. Further, we have addressed the question whether the transient condition of altered immune responsiveness can be restored by a cytokine therapy. The lymphoproliferative response towards concanavalin A (Con A) or to cross-linked anti-CD3 mAb was significantly diminished in acutely infected mice compared to immune and normal animals. This condition was associated with poor production of IL-2. In vivo treatment with recombinant IL-2 (rIL-2) resulted in marked diminution of parasitemia (from 24% +/- 6% to 8% +/- 3%) in mice during the acute phase of infection. Despite this diminution in parasitemia, 70% of the IL-2 treated mice died by day 17 post infection. In vivo treatment with rIL-2 led to a partial but significant restoration in lymphoproliferative response to TCR-mediated (cross-linked anti-CD3 mAb) or to Con A-induced stimulation in acutely infected mice. The transcripts for IL-4, IL-5, GM-CSF, and TNF-alpha were expressed in the splenocytes from acutely infected mice not treated with rIL-2. mRNAs for IL-2, IFN-gamma, IL-6, IL-10 which were not detected in acutely infected mice could be reversed by administration of rIL-2 in vivo. We suggest that some of the hyporesponsive T-cells in the acute phase of infection have the potential to be reversed, and this reversal is manifested also at the level of cytokine gene expression.

Animals↗
PubMed1995

Cell expansion and growth arrest phases during the transition from precursor (CD4-8-) to immature (CD4+8+) thymocytes in normal and genetically modified mice.

T cell early precursors belong to the CD3-CD4-CD8- triple negative (TN) thymocyte population that can be subdivided on the basis of CD44, CD25, and heat-stable Ag (HSA) expression. The kinetics and precursor product relationships of these subsets, as well as of the CD4/8low intermediates, were studied by using pulse labeling with bromodeoxyuridine (BrdUrd). The highest frequencies of DNA-synthesizing cells were found in CD44+CD25+ and CD44-CD25low or CD25- subsets. The major TN cell type (CD44-CD25high), as well as CD44+ CD25-HSAlow early precursors, contained a majority of resting cells. RAG-2-/- mice contained less cells in DNA synthesis than normal mice, and CD44-CD25-/low cells were absent. In female mice transgenic for the anti-HYTCR, CD44-CD25high cells were almost all cycling, but a high percentage of resting cells was found in CD44-CD25- cells. In days following the BrdUrd pulse, there was a reduction in the number of BrdUrd+ cells in most subsets, with the exception of the labeled CD44-CD25high cells that showed a bell-shaped curve. The kinetics and cell size evolution suggest that the majority of these cells do not give rise to CD4+CD8+ cells. In RAG-2-/- cells, the block at the CD44-CD25high stage involved all cells. In TCR transgenic (Tg) mice, no block was seen at the CD44-CD25high stage, suggesting that early expression of a complete TCR receptor precludes the normal selection step. However, another block in the differentiation process was observed at the CD44-CD25- step in TCR Tg mice, suggesting an additional selection point.

Animals↗
PubMed1995

Stochastic coreceptor shut-off is restricted to the CD4 lineage maturation pathway.

Kinetics of mature T cell generation in the thymus of normal or major histocompatibility complex (MHC) class I- or II-deficient mice were studied by the bromodeoxyuridine pulse labeling method. As previously described, the early activation and final maturation phases were found to be synchronous for the two T cell lineages, but CD4+8- cells were generated faster than CD4-8+ cells in MHC class I- and II-deficient mice, respectively. CD8 downregulation started on day 2 after cell proliferation even in the absence of MHC class II expression. CD8 downregulation thus appears to be stochastic at its beginning. By contrast, CD4 shut-off was found totally instructive, as the generation of CD4lo8+ cells with a high TCR density was not observed in class I-deficient mice. The analysis of the V beta 14 TCR frequencies in CD4/8 subsets in normal and MHC-deficient mice confirmed that CD4 and CD8 generation pathways are not symmetrical. These findings show that commitment towards the CD4+8- or CD4-8+ phenotype is controlled at the CD8lo step for the former and at the CD4+8+ double-positive stage for the latter.

Animals↗
PubMed1995

Plasmodium yoelii in mice: differential induction of cytokine gene expression during hyporesponsiveness induction and restimulation.

Acute Plasmodium yoelii murine malaria is associated with a marked depression of splenic T cell responses. The present study was undertaken to address the question if a defect in T cell proliferation results from a relative increase of a non-T cell population in the spleen or real biological changes occurring in T cells of the spleen after infection. When animals were acutely infected, the splenic cells responded poorly to cross-linked anti-CD3 mAb, Con A, and PWM stimulation. At this stage, a very limited array of cytokine was expressed. We failed to detect the transcripts for IL-2R p55, IL-2, IL-6, IL-10, and IFN-gamma in mice with acute P. yoelii malaria irrespective of the number of splenocytes subjected to RT-PCR. In contrast, late in the infection when mice cleared the parasites and became resistant to reinfection, mRNAs for the above cytokines as well as for IL-4, IL-5, GM-CSF, and TNF-alpha were detectable. During this late phase of infection, lymphocytes proliferated vigorously in response to TCR- and T cell mitogen-mediated stimulation. Surprisingly, during an early phase (as early as 3 days postinfection) with low parasitemia, before the establishment of T cell unresponsiveness, a broad array of cytokine expression including IL-2 and IFN-gamma expression as well as marked lymphoproliferative response upon T cell mitogen- and TCR-mediated stimulation was observed. When the expression of cytokine gene in freshly isolated (ex vivo) splenocytes from P. yoelii-infected animals was investigated, a similar pattern of cytokine profile was detected. We devised a methodology in which RNA from an increasing number of splenocytes (ranging from 1 to 16 million) was used to compensate for any difference in the frequency of splenic T cells between immune and acutely infected mice and to augment target molecules which could be measured simultaneously by PCR. The data presented in this study led us to speculate that "anergy" or relative increase of a non-T cell population cannot account solely for the T cell unresponsiveness in the acute phase of infection. We suggest that inactivation or/and ablation of reactive T cells may explain T cell hyporesponsiveness during acute malaria.

Animals↗
PubMed1995

[Agrypnia (organic insomnia)].

The word agrypnia, ie, organic insomnia, was first used to describe a patient with a Morvan fibrillary chorea, which is an ill-delineated syndrome. This review considers the experimental insomnia created by raphe nuclei, anterior hypothalamic, or thalamic lesions. There are some papers reporting REM and non-REM sleep reduction in man after vascular, traumatic or degenerative lesion of the pons. There is only one case of agrypnia due to a bilateral stereotatic thalamic injury. Infectious agrypnia (trypanosomiasis, Von Economo) may exist but has not been documented by polygraphic means. Fatal familial insomnia induces a precocious agrypnia and leads to death with vegetative and motor disturbances. It is associated with an abnormal prion-protein which may interfere with gabaergic synapses. Finally agrypnia in humans corresponds to either lesionnal or infra microscopic synaptic prion linked disorders.

Animals↗
PubMed1995

Sleep EEG and developmental dysphasia: lack of a consistent relationship with paroxysmal EEG activity during sleep.

In order to clarify the relationship between developmental dysphasia and EEG abnormalities, paroxysmal activities during sleep were studied in a series of 24 children with expressive developmental dysphasia (mean age 8 years) and compared to a control group of 39 children (mean age 9 years). The children of both groups were selected excluding cases with prior history of neurological disease or epilepsy. In the control group, 37 children had normal sleep EEG while 2 children had paroxysmal abnormalities. In the dysphasic group, epileptic abnormalities were observed in 9 cases, rare in 4 cases and frequent in 5 cases (density: 2.5 to 66.2% of total sleep time). Nevertheless, paroxysmal abnormalities did not reach the frequency described in the Landau-Kleffner syndrome, and it is unlikely that EEG abnormalities could have produced dysphasia.

Aphasia↗
PubMed1995

Systemic effects of epidural dexamethasone injections.

OBJECTIVES: to evaluate potential systemic effects of a single epidural injection of dexamethasone. PATIENTS AND METHODS: each of nine patients (five males and four females, mean age 47 +/- 11.8 years) admitted for sciatica was given a single epidural injection of 15 mg dexamethasone acetate. Before the injection (D0) and two (D2), seven (D7) and 21 (D21) days after the injection, the following laboratory tests were performed: serum cortisol and ACTH in the morning after an overnight fast, free cortisol in a 24-hour urine collection, fasting serum levels of glucose, triglycerides and cholesterol, serum levels of sodium and potassium. Blood pressure was measured on D0, D2, and D7. RESULTS: Serum cortisol, ACTH and urinary cortisol were profoundly decreased on D2 and D7 but normal on D21. There were no changes in fasting serum glucose, triglycerides, cholesterol, sodium or potassium levels. CONCLUSION: a single epidural injection of 15 mg dexamethasone acetate is associated with transient adrenal suppression, denoting passage of the steroid into the systemic bloodstream. However, evidence of hypercorticism is usually lacking.

Adrenocorticotropic Hormone↗
PubMed1994

Production, selection, and maturation of thymocytes with high surface density of TCR.

The main steps in intrathymic T cell differentiation have been defined using bromodeoxyuridine as a postmitotic cell tracer. Thymocytes with a high surface expression of the TCR are generated in the first 24 h after DNA synthesis. The phenotype of these TCR(high) cells was studied during 10 days by using pairs of surface markers associated with BrdUrd. During the first 2 days, TCR(high) cells were of the CD4+CD8+HSA(high) phenotype, transiently expressed the early activation marker CD69, and contained a high percentage of cycling cells. This activation step preceded the transition from CD4+CD8+ to CD4+CD8- and then to CD4-CD8+ cells, followed by progressive HSA down regulation and increase in the expression of H-2K, Qa-2, and CD45RB. The phenotypic maturation was completed in 9 days. In Mls-1a mice, negative selection of V beta 6+ cells was observed at the earliest step of TCR(high) cell generation, and positive selection of V beta 8.2+ and V beta 14+ cells took place later and was correlated to the activation step. These data suggest that high TCR expression and cell activation are necessary for positive selection and subsequent T cell maturation.

Animals↗
PubMed1994

[The influence of sleep on abnormal waking movements].

Sleep decreases considerably the abnormal movements seen during waking in the degenerative extra-pyramidal diseases. However, the electrophysiologic recordings reveal that muscular contractions are not completely abolished. This decrease parallels the reduction of the waking system which act likely as a non-specific system of amplification. One can notice that sleep modifies the characteristics of the parkinsonian tremor and that some palatal myoclonias persist during sleep.

Humans↗
PubMed1994

Slow release lanreotide treatment in acromegalic patients previously normalized by octreotide.

Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treatment of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid the inconveniences associated with either repeated sc injections or continuous sc infusions. In this study, we compared the clinical and biochemical efficacies of both drugs in a cohort of 19 acromegalic patients, considered initially as responsive to octreotide and sequentially treated with octreotide (3 sc injections of 100-200 micrograms/day) for 12 months and with SR lanreotide (30 mg, im, every 10 or 14 days) for 6 months. Before octreotide treatment, baseline plasma GH (mean +/- SE of 8 hourly samplings) was 29.0 +/- 10.0 micrograms/L and was lowered to 3.2 +/- .2 micrograms/L during the first 7 h after the first 100-micrograms sc octreotide administration. After 12 months of treatment with octreotide, 14 of 19 patients (74%) were considered normalized, as their mean individual GH profiles and insulin-like growth factor-I (IGF-I) values were within the normal range. After octreotide withdrawal for 1 week, plasma GH and IGF-I levels rose to 18.3 +/- 4.8 and 4.1 +/- 0.4 U/mL, respectively. The first 30-mg SR lanreotide im injection produced an acute suppression of plasma GH levels (mean GH value during the 7 h after the injection, 3.0 +/- 0.4 micrograms/L), not different from results previously observed after the first octreotide injection. After 3 months of treatment with 30 mg SR lanreotide every 14 days, normalization of baseline GH and IGF1 levels was achieved in 6 of 19 patients. Ten patients, who did not achieve normal GH levels, subsequently received a 30-mg SR lanreotide injection every 10 days. Among them, normalization of GH and IGF-I levels occurred in 7 of 10 patients after 3 months of such a regimen. After 6 months of SR lanreotide treatment, 13 of 19 patients (68%) were considered normalized, with mean GH and IGF-I values, respectively, of 3.1 +/- 0.4 micrograms/L and 1.5 +/- 0.1 U/mL. The overall tolerance of both drugs (glucose homeostasis and gallstone formation) was similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1993

Normal sequence of phenotypic transitions in one cohort of 5-bromo-2'-deoxyuridine-pulse-labeled thymocytes. Correlation with T cell receptor expression.

"In vivo" kinetics of T cell differentiation and TCR expression in the normal murine thymus were re-evaluated using a new technique for simultaneous detection of bromodeoxyuridine and two surface markers. The transition from CD4-8- precursors to CD4+8+ immature cells was directly observed during cell proliferation, and shown to proceed through transitory intermediates expressing no or low amounts of CD4. CD3-TCR expression also started during this transition and resulted in the production of a majority of TCRlo cells but also of a significant number (1 to 2 x 10(6) of TCRhi immature (heat-stable Ag+) thymocytes. After cessation of proliferation, the maturational transition from CD4+8+ to CD4+8- and CD4-8+ (in this order) was restricted to TCRhi cells produced during CD4+8+ cell generation. The acquisition of the single positive phenotype preceded HSA down-regulation, suggesting that maturation of TCRhi thymocytes proceeds in two separate steps. The major TCRloCD4+8+ subset appeared a dead end subset and showed no up-regulation of TCR expression at any time.

Animals↗
PubMed1993

Plasmodium yoelii in mice: antigen reactivity of CD4- and CD8-bearing T cells.

Mice infected with Plasmodium yoelii (265 BY, a nonlethal strain) after recovering from parasitemia become resistant to reinfection. In the present study, we have attempted to define the role of T cell subsets in primary vs secondary P. yoelii infection. We have evaluated the in vivo effects of selective depletion of each subset of T cells on the course of infection and also investigated the in vitro expansion of each subset in response to homologous antigen. Depletion of CD4- or CD8-bearing T cells did not result in reappearance of parasitemia in animals cured from primary infection. However, 25% of reinfected animals treated with anti-CD4 mAb, but not with anti-CD8 mAb, displayed a low level (2 to 3%) of parasitemia late in the secondary infection. The splenocyte response to P. yoelii antigen or to T-cell mitogens was impaired during patient infection, even in the 25% of CD4-depleted animals with low parasitemia. A markedly high lymphocyte reactivity to antigen was observed in mice recovered from primary infection, and this was enhanced in animals exposed to a challenge infection. In the case of animals cured from primary infection, a marked decrease in antigen-induced in vitro lymphocyte proliferation occurred in CD8-depleted but not in CD4-depleted animals when total splenic cell populations were assayed. Although less dramatic, a significant diminution in antigen reactivity was observed also with T-rich populations in CD8-depleted animals. In contrast, there was no such decrease in CD4-depleted mice. Treatment of resistant animals which were challenged with a second infection, with anti-CD4 or anti-CD8 mAbs, resulted in a significant decrease in the proliferative response to antigen by both T-rich and total cell populations. In the secondary infection, the T-rich cell populations from CD8-depleted mice responded better to P. yoelii antigen than the total cell populations, indicating an inhibitory role on the expansion of CD4+ T cells of B cells or their product(s) which were removed during T cell enrichment. The results of our study suggest that CD8-bearing T cells were more reactive in the primary infection. In the secondary infection, although both CD8+ and CD4+ T cells were antigen reactive, the latter T cell subset appeared to play a superior role in controlling the parasitemia.

Animals↗
PubMed1993

A novel CD45RA+CD4+ transient thymic subpopulation in MRL-lpr/lpr mice: its relation to non-proliferating CD4-CD8-CD45RA+ tumor cells.

MRL-lpr/lpr mice have hypertrophied lymph nodes comprising CD4-CD8- T cells. In addition, they contain CD4+CD8- T cells co-expressing the CD45RA marker. The correlation between these two subpopulations has been difficult to assess. We analyzed the expression of CD45RA (with the RA3-2C2 antibody) in various thymic and peripheral T cell subsets, using three-color immunofluorescence. We showed that in lpr mice (i) a transient CD4+CD8- thymic subset co-expresses CD45RA during the course of the disease, and (ii) thymic as well as peripheral CD4-CD8- and CD4+CD8- T cells brightly express CD45RA; furthermore (iii) in the lymph nodes, during lymphadenopathy, CD4+CD8-CD45RA+ T cells show a broad range of the CD4 fluorescence intensity, and (iv) the increase in MHC class II expression is restricted to CD45RA-T cells of the thymus and lymph nodes of lpr mice. Taken together, these data suggest that the CD4+CD8-CD45RA+ population might generate the CD4-CD8- tumor cells. In addition, using the bromodeoxyuridine labeling technique, we demonstrate that these cells are not the result of increased proliferation.

Animals↗