Biomedical subjects
Publications and source records attributed to F Gaillard.
Cholecystoenteric fistulas are often not diagnosed preoperatively and delineation of fistula can have an influence on surgical planning. We report a case of cholecystocolonic fistula diagnosed preoperatively using CT-i.v. cholangiography and review the published reports.
Allogeneic embryonic CNS tissue grafts placed in the mature brain are classically considered to lack significant long-range efferents. This problem was reexamined using 'green' cells from mice expressing ubiquitously an 'enhanced' green fluorescent protein as an alternative to classical tract tracing methods. The present study shows that fetal cortical neurons (E15; occipital origin) grafted in the occipitoparietal region of the adult cortex project massively throughout ipsilateral telencephalic structures. Two out of the nine grafted subjects had additional but sparse efferents in the visual thalamus, superior colliculus and pons.
Hydrophobicity, lubrication and anticorrosion properties of steel substrates have been obtained by a deposition of thin film (i.e. by mechanochemical treatment) at room conditions. Stearic acid and paraffin were chosen as reactive molecules. Different abrasive powders were selected to generate active sites on the treated surfaces for adsorption of the reactive molecules and then, the results were compared. The surfaces were analyzed by reflection-absorption infrared spectroscopy (RAIRS). The results emphasize that, a thick layer of mixed stearic acid/paraffin was deposited onto the metallic surface after the treatment. After hexane rinsing we could only detect a very thin layer of oriented stearic acid molecules chemically adsorbed onto the metallic surface and which engages strong interactions with it. Whereas, RAIRS only provides molecular analysis, the XPS technique was complementary for discriminating the different surfaces. It was possible to show differences in thickness as well as in coverage according to the size and shape of abrasive particles. Furthermore, we could conclude that deposit layer is not uniform. Defects were always present and were dependent on abrasive powders used. Then wettability was assessed as a way to test the homogeneity of thin films generated by the mechanochemical treatment. In agreement with theoretical data, receding contact angle was very dependent on the defects in the deposited film. If holes or aggregates were increased in the deposit layer, the receding contact angle was decreased while advancing contact angles and equilibrium contact angles remained constant. A very important point for technological applications was that the homogeneity of the deposited film was governed by abrasive powder involved in mechanochemical treatment and contact angle values were a direct measurement of the homogeneity of surfaces generated by mechanochemical treatment.
Intravitreal injection of the microglia inhibitor tuftsin 1-3 leads to an increase in retinal ganglion cell axonal regeneration into peripheral nerve grafts and a decrease in phagocytic cells in the retina. However, the relation of phagocytic cells and particularly microglia towards axonal regeneration remains unclear. Initially, to assess this, tuftsin 1-3's effect on axonal regeneration was reexamined by doing a dose-response study. Optimal doses were found to be 2.5 microg/ml and 250 microg/ml in rats and hamsters respectively. We then studied retinal phagocytic cells in rats. Microglial cells were classified as resting or activated based on their morphology following OX42 immunolabelling. In controls, most microglial cells were in the resting state. Optic nerve cut led to an increase in the total number of microglia and a ten-fold elevation in the proportion of activated cells; changes were more pronounced at the optic nerve stump. Anastomosis of an autologous segment of sciatic nerve to the stump of the freshly cut optic nerve minimized the overall increase in microglia, and combined with 2.5 microg/ml tuftsin 1-3, lead to a marked blunting of activation. Preservation within the retina of a higher proportion of resting over active form of microglia, and not the prevention of microglial proliferation per se, may be a crucial factor in allowing additional retinal ganglion cell axons to regenerate into peripheral nerve grafts.
PURPOSE: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1983 to 1998, 34 patients received TAI (n = 22) or TBI (n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1-5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. RESULTS: Mean follow-up from TAI or TBI was 120 months (range, 6-180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. CONCLUSION: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.
Physiologically responsive grafts of embryonic (E16) occipital neurons placed into the visual cortex of adult rats were shown previously (Gaillard et al., 1998, Restor. Neurol. Neurosci. 12: 13-25) to receive a predominant (93-97%) cortical input from the infragranular layers V-VI. The present paper examines whether this specific pattern of connections is related to some process of maturation of the host cortex. Pieces of embryonic (E16) occipital cortical tissue were grafted into the visual cortex of neonate (P0), 1-week-old (P7), and adult (P120) subjects. Four months later, graft responsiveness was assessed through field potential recordings and host-to-graft afferents were labeled with a retrograde tracer (cholera toxin subunit B). The data show first that afferents to physiologically active grafts originate about equally from both supra- and infragranular cortical layers in newborn subjects and second that supragranular neurons contribute only 20 and 1.5% of these inputs in P7 and P120 recipients, respectively. This strong upside-down laminar shift of afferents may correlate with the layout of subsets of host neurons that at a given developmental stage would have the intrinsic capacity to regrow an axon. Substantial axogenesis and synaptic stabilization of host-to-graft cortical afferents appear possible only within the critical period for the supragranular neurons but may occur throughout life for the infragranular neurons.
We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19+CD5-CD23+/- immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19+CD5+CD23+ phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG+ with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. VH gene analysis was performed in eight patients to investigate the clonal origins of tumour cells. All cases utilized the VH3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. VH gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage and others as IgG-positive cells only.
Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure.
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To assess an unequivocal diagnosis of mantle cell lymphoma (MCL), we have developed a fluorescence in situ hybridization (FISH) assay, enabling the demonstration of t(11;14)(q13;q32) directly on pathological samples. We have first selected CCND1 and IGH probes encompassing the breakpoint regions on both chromosomes. Then, we have defined experimental conditions enabling us to obtain bright clear-cut signals in all of the samples, independently of the initial fixation conditions. We have analyzed single-cell suspensions from 26 formalin-fixed, paraffin-embedded MCL samples with this set of probes. In all cases, we have found a fusion signal (ie, a t(11;14)(q13;q32) translocation) in 14% to 99% of cells (median, 87%). So far, IGH-CCND1 fusions have been detected in all of the 51 MCL patients that we have analyzed by FISH (either on paraffin-embedded tumor samples or on peripheral blood samples). Regarding the low sensitivity of other techniques used to diagnose t(11;14)(q13;q32) (ie, 70% to 75% for cytogenetics and 50% to 60% for polymerase chain reaction), our FISH assay is by far the most sensitive technique. Moreover, because of the quality of the fluorescent signals and the rapidity of the experiment, this technique is widely applicable, even in routine cytogenetics or pathology laboratories. As MCL patients are usually refractory to standard therapy, an unambiguous diagnosis is needed to propose adapted therapeutic strategies, and this highly sensitive assay may be of great value for accurate diagnosis in difficult cases.
We determined whether the sensitivity of the ipsilateral type II units of Rana esculenta to prey (W/H-oriented bars) and non-prey (A/V-oriented bars)-like targets remains invariant under various experimental conditions. We show that the shape of the 'discrimination' curve is largely unaffected by the level of general illumination and by the background texture. An increase in the stimulus velocity and in the width of the bars moderately affects the salient points (negative peak and preference reversal) of the curve, but does not alter the overall configurational preference of these units. As for retinal ganglion cells: (i) this curve expresses better a 'contrast' between two vertically oriented edges of different dimensions than a 'contrast' between two edges of equal dimension but of different orientation; and (ii) the experimentally induced variations can be explained on the basis of the spatial and temporal properties of the neuronal elements forming the antagonistic center-surround arrangement of the receptive field.
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PURPOSE: To evaluate the therapeutic efficacy of moderate-dose total abdominopelvic irradiation (TAI) in a retrospective series of pretreated non-Hodgkin's lymphomas (NHL). METHODS AND MATERIALS: From 1977 to 1994, 45 patients received TAI after failure of chemotherapy (CT). According to the Working Formulation, 10 patients were diagnosed with class A (group I), 19 with class B, C, or D (follicular) (group II), and 16 with class E or more severe (group III) NHL. Irradiation consisted of two daily fractions of 0.80 Gy each for a total dose of 20 Gy. RESULTS: Mean follow-up after TAI was 102 months (range 8-156). For the entire group, the complete response (CR) rate was 66%, the partial response (PR) rate 29%, 10-year overall survival (OS) 35%, 10-year disease-free survival (DFS) 29%, and median survival 32 months. When results between subgroups were compared, CR was 70% in group I, 84% in group II, and 44% in group III; and survival was statistically higher in group II than in groups I and III: 10-year OS 52% vs. 10% (p < 0.01) and 31% (p < 0.05), respectively, 10-year DFS 37% vs. 10% (p < 0.03) and 19% (p < 0.05), respectively. Grade III or IV complications were gastrointestinal in 27% of patients and hematologic in 25%. CONCLUSION: Large-field irradiation in moderate doses could provide an alternative to bone marrow transplantation in refractory NHL, especially in cases showing a follicular growth pattern.
The chromosomal translocation t(11;14)(q13;q32) fuses the IGH and CCND1 genes and leads to cyclin D1 overexpression. This genetic abnormality is the hallmark of mantle cell lymphoma (MCL), but is also found in some cases of atypical chronic lymphocytic leukemia (CLL), characterized by a poor outcome. For an unequivocal assessment of this specific chromosomal rearrangement on interphase cells, we developed a set of probes for fluorescence in situ hybridization (FISH). Northern blotting was performed for analysis of the cyclin D1 expression in 18 patients. Thirty-eight patients, with either a typical MCL leukemic phase (17 patients) or atypical CLL with an MCL-type immunophenotype, i.e., CD19-, CD5+, CD23-/low, CD79b/sIgM(D)++, and FMC7+ (21 patients), were analyzed by dual-color interphase FISH. We selected an IGH-specific BAC probe (covering the JH and first constant regions) and a commercially available CCND1 probe. An IGH-CCND1 fusion was detected in 28 of the 38 patients (17 typical MCL and 11 cases with CLL). Cyclin D1 was not overexpressed in two patients with typical MCL and an IGH-CCND1 fusion. In view of the poor prognosis associated with MCL and t(11;14)-positive CLL, we conclude that this set of probes is a valuable and reliable tool for a rapid diagnosis of these entities.
This report presents the results of neural transplantation experiments that were designed either to study neural developmental phenomena or to appraise the possible restorative capacity of grafts. The first part of the report deals with the findings of transplantation studies that were performed in newborn recipient rats in an attempt to determine the importance of extrinsic or intrinsic factors in the process of areal cortical differentiation. More precisely, we examined the extent to which extrinsic signals drive the pattern of efferent connections of neurons residing in different cortical areas. In the first experiment, we examined the general distribution pattern of efferents arising from homotopic as compared to heterotopic transplants of embryonic cortical tissue placed into the frontal cortex of newborn rats. Our findings indicated that embryonic occipital neurons transplanted heterotopically into the sensorimotor cortex: (a) only rarely contacted normal targets of the motor cortex, (b) systematically projected towards normal targets of the visual cortex, and (c) distributed fibers to structures normally receiving fibers from both the motor and visual cortex, either exclusively into the visual corticorecipient zone of the structure or into both the visual and motor corticorecipient zones. In the second experiment, we attempted to assess the densities of the spinal projections arising from homotopic or heterotopic transplants implanted into the frontal or occipital cortex of newborn rats. We provided evidence that transplants of embryonic neocortical neurons of frontal origin developed and maintained a spinal cord projection whatever their rostrocaudal position within the host neocortex, whereas transplants of occipital origin did not maintain a significant spinal cord projection in adulthood. Finally, in the third experiment, we analyzed the laminar and tangential distribution of the tectal projections developed by transplants of embryonic occipital cortex placed into the primary or secondary subdivisions of the occipital cortex of newborn rats. Abnormalities in the laminar and/or tangential organization of the tectal distribution of the transplant efferents were systematically found. Using these different transplantation paradigms, we provided increasing evidence that, in their heterotopic location, the embryonic neurons retain some of the developmental characteristics corresponding to their embryonic cortical site of origin. Our findings strongly suggested, therefore, that there is an early specification of neocortical neurons to develop area-specific efferents. In conclusion, converging lines of evidence suggest that regional differences in the neuroepithelium are predetermined early in development, thus leading to cerebral cortex parcellation, as hypothesized by Rakic (1988). In the second part of the report, we describe the results of a series of experiments dealing with the consequences of grafting embryonic cortex into the damaged cortex of adult rats. These effects were examined from an anatomical, metabolic, behavioral, and electrophysiological point of views. The experiments were conducted using either the frontal or the visual cortex as models to appraise the functional integration of the grafts into the motor or visual circuits, respectively. The first study was undertaken to examine the capacity of transplants of embryonic frontal neocortical tissue placed into the frontal cortex of an adult recipient to develop efferents into the host CNS. The results indicated that transplants of fetal neocortex placed into adult CNS had the capacity to develop efferents which seemed to grow over significant distances within the host corpus callosum but, in most cases, failed to penetrate deeply into the gray matter. The density of the efferent projections was, however, far weaker than that seen in newborn hosts. In the second study, the 2-deoxyglucose (2-DG) technique was used to examine the functional integration of hom
Teeters and Arbib (Bio Cybernet 1991;64:197-207) presented a model of the anuran retina which qualitatively accounts for some of the characteristic response properties used to distinguish ganglion cell type in anurans. Teeters et al. (Vis Res 1993;33:2361-2379) tested the model's ability to reproduce data of Ewert and Hock (Exp Brain Res 1972;16:41-59) relating toad R2, R3 and R4 ganglion cell responses to moving worm, antiworm and square-shaped stimuli of various edge lengths for stimulus shape and size dependency. In this paper we provide an exhaustive analysis of the performance of the modeled R3 cells with respect to most of the known qualitative and quantitative physiological properties of natural R3 ganglion cells. We also introduce several relevant predictions of the model relating different responses of R3 cells under the effect of changes in different model components. In some cases the predictions have been tested in neurophysiological experiments.
Discrimination of 'prey' (bars elongated in the direction of movement; W- or H-orientation) and 'non-prey' (bars perpendicular to the direction of movement; A- or V-orientation) stimuli in freely moving amphibians is velocity-invariant. Whether or not this phenomenon is present in cells belonging to a general decision making neuronal process remains questionable. Present investigations report the effect of the angular velocity of the stimulus on the discrimination function of class R3 (transient ON-OFF) retinal ganglion cells. The main conclusions of this work are the following: (1) irrespective of the angular velocity, class R3 neurons always prefer vertically (A-) to horizontally (W-) oriented stripes as long as the stimulus length remains inferior to the receptive field size; (2) this preference for small A-stimuli is best expressed when stimuli are moved at V = 7.6 degrees/s; (3) a preference reversal is induced by stripes longer than the receptive field via a dual process involving both spatial and temporal mechanisms; (4) this preference reversal is velocity-dependent: the longer the bar, the faster the velocity should be.
From 1991 to 1997 18 consecutive patients with well-defined mantle cell lymphoma (MCL) underwent high-dose therapy with unpurged autologous (17 patients) or allogeneic (one patient) stem cell transplantation. Tissue sections were reviewed for morphology, immunophenotype, cyclin D1 and P53 expression as well as proliferation index (PI). Median age of patients was 47 years (range 40-60). Sixteen had stage IV disease with bone marrow involvement in 12 and performance status was > or =1 in 12 patients. At the time of high-dose therapy 10 patients were in first partial response (PR), one was in second complete remission (CR), four were in second PR and three were refractory to conventional anthracycline-containing chemotherapy. The conditioning regimen consisted of TBI plus chemotherapy in 13 patients and chemotherapy only (BEAM) in five patients. No treatment-related deaths were observed. With a median follow-up of 36 months (range 13-80) after transplant, disease-free survival (DFS) and overall survival (OS) are estimated to be 48 and 80% at 4 years, respectively. Significantly better results are achieved for patients transplanted after a TBI containing regimen with a 4 year OS and DFS estimated at 89 and 71%, respectively compared to 60 and 0% respectively for patients who were conditioned without TBI (P = 0.07 for OS and P < 0.0001 for DFS). There is a trend towards better DFS when the transplant is performed in PR1 (4 year DFS: 80% with eight patients out of 10 in continuous CR 13 to 80 months, median 36 months after transplant) compared to more advanced stages (4 year DFS: 18% with only three patients out of eight in continuous CR 16, 17 and 58 months after transplant). Blastic histology and P53 overexpression are also associated with a trend towards a worst prognosis.