Biomedical subjects
Publications and source records attributed to F Faure.
Splenic hemangioma is a very rare neoplasm in children. We report three cases of splenic hemangioma, two of solitary hemangioma and one of hemangiomatosis. Two patients had hematologic disorders related to hemangioma. Imaging findings of this entity are presented and discussed with emphasis on pathologic correlation.
The results of MRI and MIBG scintigraphy performed on the spine of 14 children with neuroblastoma are reported. In 6 cases of diffuse spinal bone marrow tumor infiltration, diagnosis is easier with MIBG scintigraphy than with MRI. In 5 cases, MRI detected hyposignal of the vertebral body without any spinal abnormality on MIBG scintigraphy. A discussion of the reasons for negative MIBG scintigraphy is presented and in these 5 cases, it is suggested that a lateral view of MIBG scintigraphy and HMDP-Tc99m scintigraphy may be performed, even vertebral body biopsy in order to assess bone marrow tumoral infiltration.
Three pediatric cases of malignant rhabdoid tumor of the neck are described. Clinical data and imaging findings (US, CT and MRI) are stressed. The mass was well defined, containing punctate calcifications in two cases and encasing the vessels in two other cases. Two patients were treated with a chemotherapy regimen according to MMT 89 SIOP protocol, one had chemotherapy and radiotherapy. Two children died of progressive disease; the remaining child who had complete surgical removal of the tumor is on remission 17 months after diagnosis.
An open-label noncomparative clinical study was conducted to evaluate the efficacy and tolerance of ioversol (Optiray 300), a new low-osmolality non ionic contrast medium, in body contrast-enhanced CT scanning in infants and children. Fourty pediatric patients who required contrast-enhanced CT scanning for evaluation of chest, abdominal or pelvic masses participated in the study. The vascular enhancement was judged to be excellent or good in 72.5% of the cases and the CT scans were judged to be diagnostic in 95% of the cases. Ioversol was well tolerated in the study with only two mild adverse reactions (nausea and vomiting, and metallic taste).
Three pediatric cases of hydatic cyst of the kidney are reported. This is a very rare condition in children. Usually, the presentation is a cystic space-occupying lesion of the kidney. Several diagnostic methods are available but it is stressed that ultrasonography may be sufficient. Surgical treatment is still necessary.
A new case of duodenal atresia with gas below the obstruction is reported. This apparently contradictory feature is due to a bifid termination of the common bile duct in the duodenum, air by-passing the atretic area. The anomaly was proven by operative cholangiography.
Placental transfer of unfractionated heparin (UH), of low molecular weight heparin CY 216 (LMWH) and of Dermatan sulphate (DS) was studied using the human perfused placental cotyledon model. Two different techniques were used to assess the transfer: labelled molecules and biological activities as measured by antifactor Xa or antifactor IIa activities. No biological activity was present in the fetal circulation, for any of the drugs used; however, very low fractions of the perfused radioactivity were recorded, 0.76% +/- 0.36%, 1.46% +/- 1.44% and 2.37% +/- 0.89% for DS, UH and LMWH, respectively.
The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.
Previously we have shown that a small fraction of human peripheral T cells expresses a surface receptor recognized both by the BMA031 mAb, specific for a TcR alpha/beta framework epitope, and by the A13 mAb, putatively specific for an epitope encoded by the V delta 1 gene segment. An interleukin 2-dependent polyclonal cell line (termed T2) was derived from such A13+BMA031+ circulating lymphocytes. The molecular characterization of the TcR chains expressed by T2 cells demonstrated indeed that the V delta 1 gene (one of the two major V delta genes) was transcribed with the C alpha gene segment. In the T2 polyclonal cell line, distinct V delta 1/C alpha transcripts were all found to include the same J alpha segment suggesting the existence of "hybrid" TcR alpha/delta chains encoded by unique V delta 1/J alpha rearrangements. The present study was designed to characterize further the V delta 1/J alpha rearranged genes expressed in A13+BMA031+ cells. Three additional cell lines were generated from peripheral blood of distinct adult healthy donors. Using the anchored polymerase chain reaction, it was found that 17 different J alpha segments were used in the 20 V delta 1J alpha C alpha transcripts which have been studied. Together, these data indicate that V delta 1 is a "mixed" (i.e. alpha/delta) TcR V segment which can join with most (if not all) J segments in the alpha/delta locus. In addition, it can be definitely concluded that the A13 mAb recognizes a V delta 1-encoded antigenic determinant and not a V delta 1J epitope (i.e. it can be defined and used as an anti-V delta 1 mAb, as opposed to reagents such as for example delta-TCS-1).
CT-scan examinations have been performed in 25 children with slipped capital femoral epiphysis (SCFE) and in 127 children in an out-patients orthopaedic consultation. A low femoral anteversion (FA) was present in SCFE. This morphological abnormality, in association with other factors, could explain the production of SCFE at the moment of the most important fragility of the upper femoral growth plate, which is puberty. A statistical analysis showed that the risk of SCFE was distinctly greater, even for the contralateral hip when FA was low.
In the present study, we have characterized the reactivity of two mAbs that are directed at the human TCR-gamma/delta. These reagents, designated anti-A13 and anti-TiV delta 2, were found to recognize antigenic determinants encoded by the TCR V delta 1 and V delta 2 gene segments, respectively. Immunofluorescence analyses performed with the antibodies confirmed that, in the TCR-gamma/delta+ cell subpopulation, the expression of V delta 2+ delta chains is largely predominant, as compared with the V delta 1+ counterparts. However, these experiments led to an apparently discrepant finding. Indeed, the total number of cells recognized by the anti-A13 plus the anti-TiV delta 2 antibodies was often greater than that detected with anti-TCR-delta 1, a reagent specific for a constant epitope of the human delta chain. Further investigation showed that the presence of a sizeable peripheral lymphocyte subset coexpressing the BMA031 and the A13 epitopes. Because the former antibody is known to recognize an invariant antigenic determinant of the TCR-alpha/beta dimer, these results suggested that the V delta 1 gene segment may be expressed with either C delta or C alpha. This hypothesis was confirmed using T2, an IL-2-dependent BMA031+ A13+ polyclonal cell line developed from peripheral blood of a healthy adult donor. Indeed, T2 cells were found to have productively rearranged the V delta 1 gene. Together, results of Northern blot analysis and cDNA cloning indicated that V delta 1 was expressed in these cells as part of a 1.6-kb full-length message including J alpha-C alpha segments.
It has been shown recently that one gamma/delta cell line, termed IDP2, derived from a immunodeficient patient recognizes the CD1c molecule on the surface of target cells. In light of these data, we have tested 43 cloned and 11 polyclonal gamma/delta cell lines derived from peripheral blood of 19 donors following nonspecific mitogenic stimulation. In this panel, which included lymphocytes expressing various combinations of gamma and delta chains, only one clone, termed J2B7, was found to interact with target cells via a CD1c-dependent recognition pathway. These J2B7 lymphocytes have, like IDP2, a delta chain which results from the frequent V1/J1 rearrangement while they use a distinct V gamma gene segment. The data support the view that the CD1c major histocompatibility complex "class I-like" gene product does not have a pivotal contribution to the repertoire of peripheral blood gamma/delta cells in adult individuals.
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The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.
We have identified in earlier studies two V delta rearrangements corresponding to a 4.5-kb Eco RI fragment detected with a V delta1 probe and to a 7-kb Eco RI band detected with a V delta2 probe. These rearrangements have been found in two human T cell clones, F6C7 and G6, displaying surface phenotypes unfrequent in human peripheral blood, namely Ti gamma A+ BB3- (F6C7) and Ti gamma A- BB3+ (G6). Herein, we report the sequences of the functional transcripts encoded by these rearranged genes and show that the 4.5- and the 7-kb Eco RI fragments correspond to V1/D3/J delta 3 and to V2/D3/J delta 3 recombinations, respectively. In addition, we have sequenced the V2/D3/J1/C delta transcripts expressed in two clones, AB12 and VTC, which have a Ti gamma A+ BB3+ surface phenotype corresponding to that of most gamma/delta peripheral lymphocytes. Analyses of the delta transcripts expressed by these four cells further strengthen the hypothesis that anti-BB3 and anti-delta-TCS-1 monoclonal antibodies recognize a V delta 2- and a V1/(D)/J delta 1-encoded epitope, respectively. Sequence of the gamma transcripts expressed by AB12 and F6C7 cells shows that they encode a V9/JP/C gamma 1 chain. Finally, we confirm that non-combinatorial diversity in the gamma and delta proteins is generated by both junctional flexibility and N-region addition without any somatic mutation.
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Three mAb, anti-Ti gamma A, anti-TCR delta 1, and anti-delta TCS1, have been developed against the CD3-associated gamma/delta molecular complex. One of this antibody anti-Ti gamma A is specific for an epitope encoded by the V9 gamma-gene. The two others react with the delta-chain but their fine epitopic specificity has not been characterized previously. In the present study, we have compared the surface expression of these three antigenic determinants on 27 cloned and 5 polyclonal CD3+ TCR gamma/delta + cell lines derived from human peripheral blood of 13 distinct individuals. It was found that all CD3+ TCR alpha/beta- clones and polyclonal cell lines tested were recognized by anti-TCR delta 1. In contrast, only a fraction of both clones and cell lines reacted with either anti-Ti gamma A or anti-delta TCS1 mAb. In fact reactivity of the latter reagents was found to be mutually exclusive on the cell panel. Northern blot analysis of RNA extracted from a series representative clones showed a positive correlation between the surface expression of the delta TCS1 epitope and the transcription of the V-delta gene isolated from the IDP2 cell line. These data support the view that anti-TCR delta 1 can be used to positively define the entire TCR gamma/delta+ fraction. Moreover, the reciprocal reactivity of anti-delta TCS1 and anti-Ti gamma A on cultured cell lines suggests that these reagents should delineate in human peripheral blood distinct, essentially non-overlapping, subsets. Taken together, the present results indicate that the complementary use of these three antibodies will be helpful to further characterize the TCR gamma/delta + peripheral lymphocyte fraction.
We have identified, in a healthy individual, a sub-population of human peripheral lymphocytes which surface express a CD3-TCR-gamma complex recognized by anti-Ti gamma A mAb, while being unreactive with a phycoerythrin-conjugated anti-CD2 antibody with T11/1 specificity. Further immunofluorescence analyses performed on uncultured cells indicated that such a putative CD2-CD3+ phenotype was restricted to a fraction of those T lymphocytes which carry a surface receptor of the "second family" (gamma/delta). The actual lack of CD2 expression was confirmed by a subsequent series of cloning experiments which showed that none of the three well characterized CD2 epitopic clusters, namely T11/1, T11/2, and T11/3, were detectable on the surface of the relevant cells. The cultured CD2-, CD3+/TCR gamma + lymphocytes were found to display, as well as their CD2+ counterparts, both non-MHC-restricted cytotoxic function and proliferative responses induced via the gamma receptor complex. In contrast, the proliferative capacity of the CD2-, CD3+/TCR-gamma + cells observed in a culture system designed for in vitro expansion of lymphocytes with undefined specificity was extremely limited. This may relate to an impaired interaction of the CD2- cloned lymphocytes with lymphocyte function-associated (LFA)3+ irradiated cells present in the feeder layer. Further characterization of such minor CD2- T lymphocytes subsets may help to better understand the biologic relevance of the CD2/LFA3 pathway of cell-cell interaction.