Biomedical subjects
Publications and source records attributed to C Vincent.
We report a case of epidural metastasis with left renal vein invasion. This nonsymptomatic venous involvement was detected by ultrasonography and confirmed at CT and MR imaging. Such an unusual cause of renal vein tumor thrombus occurred through a lumbar vein which represents one of its usual collateral branches.
Dorsoventral asymmetry in flowers is thought to have evolved many times from a radially symmetrical ancestral condition. The first gene controlling floral asymmetry, cycloidea in Antirrhinum, has been isolated. The cycloidea gene is expressed at a very early stage in dorsal regions of floral meristems, where it affects growth rate and primordium initiation. Expression continues through to later stages in dorsal primordia to affect the asymmetry, size and cell types of petals and stamens.
Knowing that several CD4 mAbs may delay allograft rejection in the absence of circulating CD4+ lymphocyte depletion in vivo, we investigated the mechanisms whereby CD4 mAbs can interfere with the development of alloreactive T cells in the mixed lymphocyte reaction (MLR). In agreement with previous reports, CD4 mAbs of different species (mouse, rat, humanized), isotypes (IgG1, IgG2a, and IgG2b) and different epitope specificities decreased 3H-TdR incorporation in MLR, using monocyte-depleted or CD4+ T lymphocyte-enriched blood mononuclear cells as responders. Those effects were achieved at nonsaturating mAb concentration and were still demonstrable upon delayed addition of CD4 mAbs. However, CD4 mAbs decreased neither the number of blast cells nor the expression of CD25 (the alpha chain of IL-2 receptor), indicating that initial activation events leading to blast transformation were not affected. Determination of cytokine gene expression by non competitive quantitative RT-PCR and measurement of protein concentration in supernatants demonstrated that CD4 mAbs did not decrease IFN-gamma induced by alloactivation. However IL-2 concentration was decreased in all supernatants whereas IL-2 mRNA expression, only slightly decreased at 24 hr, and dropped after 72 hr. IL-5 and IL-10 mRNAs, equally expressed by stimulated or nonstimulated responder cells, were not affected by CD4 mAbs. IL-4 mRNA was not detectable. Furthermore, addition of rIL-2, rIFN-gamma or rIL-4 did not overcome proliferation inhibition. The data provide a novel insight into the mechanisms of CD4 mAbs immunosuppresssion that associates a decrease of IL-2 expression with an IL-2 resistant blockade of the progression of activated CD4+ T cells from the G1 to the S phases of the cell cycle.
Fluorescence in situ hybridization analysis of an 8q translocation breakpoint, dir ins(8)(q24.11;q13.3;q21.13), carried by an individual presenting with Branchio-Oto-Renal (BOR) syndrome, resulted in the identification of an associated deletion. The generation of a YAC contig and the isolation of overlapping recombinant P1 and lambda phage clones from the region allowed further characterization of this deletion. Its size was estimated to be between 470 and 650 kb, and it was flanked by the two polymorphic markers D8S1060 and D8S1807. This mapping led us to reevaluate the localization of the gene responsible for BOR syndrome and has now focused the search for the BOR gene to within the limits of this deletion.
Flowering plants exhibit two types of inflorescence architecture: determinate and indeterminate. The centroradialis mutation causes the normally indeterminate inflorescence of Antirrhinum to terminate in a flower. We show that centroradialis is expressed in the inflorescence apex a few days after floral induction, and interacts with the floral-meristem-identity gene floricaula to regulate flower position and morphology. The protein CEN is similar to animal proteins that associate with lipids and GTP-binding proteins. We propose a model for how different inflorescence structures may arise through the action and evolution of centroradialis.
It has been recently suggested that soluble tumour necrosis factor receptors (sTNF-Rs) may represent prognostic factors in cancer. In malignant melanoma, the intercellular adhesion molecule (ICAM-1) has been described as involved in progression of the disease and is upregulated by TNF alpha. We report in this study the serum concentrations of sTNF-R1 and sTNF-R2 in 32 patients with primary melanoma and in 21 patients with metastatic melanoma, in correlation with those of soluble ICAM-1 (sICAM-1). Significantly raised sTNF-R1 levels were detected only in patients with metastatic melanoma compared with normal controls (P < 0.002), whereas sTNF-R2 levels were increased both in primary and metastatic melanoma (P < 0.001). The ratio of type 2 to type 1 proteins increased in malignant melanoma compared with the controls but remained constant with the progression of the disease. A correlation between sTNF-Rs and sICAM-1 concentrations in patients' sera was observed in metastatic melanoma. The combined adverse effects of these soluble proteins on normal immune effector functions may contribute to tumour progression.
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The recessive mode of transmission accounts for approximately 75% of inherited non syndromic deafness cases. We have previously designed the conditions for linkage studies of this highly heterogeneous disorder [Guilford et al. (1994) Nature Genet. 6, 24-28]. Here, using a similar approach, we have studied the segregation of a gene responsible for congenital, profound and fully penetrant sensorineural deafness in a consanguineous family living in an isolated region of Lebanon. A maximum lod score of 8.03 (theta = 0.00) was detected with a new polymorphic marker, AFMa052yb5 (D2S2144). Observed recombinants and homozygosity mapping define a maximum interval of 2 cM for this gene, DFNB6, which lies between AFMb346ye5 (a new polymorphic marker) (D2S2303) and AFM254vc9 (D2S174) on chromosome 2p22-23.
Hispanic women constitute one of the fastest growing and most diverse groups in the United States, representing many countries of origin and cultural practices. The purpose of this evaluation study, using an ex post facto design, was to examine well-being during pregnancy and pregnancy outcomes for a cohort of 113 Hispanic women receiving perinatal care at the clinic of a community hospital in an old industrial city in the Northeast. The received adequacy of prenatal care for the study sample women was very high. The low-birthweight rate was lower than for the study hospital, the study city, the state, and the entire United States. The results of this study demonstrate the favorable effects of a comprehensive, interdisciplinary, and culturally sensitive model of prenatal care on these women's well-being and birth outcomes. Findings also support the need for an outreach program targeted at hard-to-reach women in the inadequate, received-care group and women with later initiation of care.
Over 250 patients from three complementary medicine practices-acupuncture, osteopathy and homoeopathy-completed a questionnaire rating 20 potential reasons for seeking complementary treatment. The reasons that were most strongly endorsed were "because I value the emphasis on treating the whole person'; "because I believe complementary therapy will be more effective for my problem than orthodox medicine'; "because I believe that complementary medicine will enable me to take a more active part in maintaining my health'; and "because orthodox treatment was not effective for my particular problem'. Five factors were identified, in order of importance: a positive valuation of complementary treatment, the ineffectiveness of orthodox treatment for their complaint, concern about the adverse effects of orthodox medicine, concerns about communication with doctors and, of less importance, the availability of complementary medicine. Groups were compared, using analysis of covariance to control for demographic differences between the three patient groups. Osteopathy patients' reasons indicated they were least concerned about the side effects of orthodox medicine and most influenced by the availability of osteopathy for their complaints. Homoeopathy patients were most strongly influenced by the ineffectiveness of orthodox medicine for their complaints, a fact which was largely accounted for by the chronicity of their complaints. Results are discussed in terms of the limited research in this area. Future studies should separate the reasons for beginning complementary treatment from the reasons for continuing it. It is possible, for instance, that the failure of orthodox medicine is the strongest motive for seeking complementary treatment but that, once treatment has been experienced, other more positive factors become more important.
The effect on human peripheral blood mononuclear cells (PBMCs) of neutral glycosphingolipids extracted from metacestodes of the parasite Echinococcus multilocularis was investigated. Neutral glycosphingolipids inhibited [3H]thymidine uptake by human PBMCs upon stimulation by mitogens such as phytohemagglutinin A and pokeweed mitogen or by allogeneic Burkitt B cells. This effect was dose dependent and was related to a decrease in interleukin 2 (IL-2) synthesis, the expression of IL-2 receptors (CD25) being unmodified. Addition of exogenous recombinant IL-2 restored the cell proliferation. Partial inhibition of immunoglobulin G (IgG), IgA, and IgM synthesis was observed in the supernatant of cell culture in association with the inhibitory effect. Identification of active subfractions contained in the neutral glycosphingolipid fraction was also studied in relation to cell viability. The free ceramide fraction had an inhibitory effect, in part related to cell lysis, particularly at high concentration, while the monogalactosylceramides had a paradoxical effect: as an activator at low concentrations and as an inhibitor at high concentrations, with limited cell survival. The immunogenic neutral glycosphingolipids containing at least two carbohydrate residues, all having a structure based on Gal beta 1-->6Gal, were inhibitors of PBMC proliferation and showed good cell survival. These results suggest that parasite neutral glycosphingolipids may play an immunologically relevant role in alveolar hydatid disease.
This study first shows a striking parallel between the expression patterns of the Bmp4, Msx1 and Msx2 genes in the lateral ridges of the neural plate before neural tube closure and later on, in the dorsal neural tube and superficial midline ectoderm. We have previously shown that the spinous process of the vertebra is formed from Msx1- and 2-expressing mesenchyme and that the dorsal neural tube can induce the differentiation of subcutaneous cartilage from the somitic mesenchyme. We show here that mouse BMP4- or human BMP2-producing cells grafted dorsally to the neural tube at E2 or E3 increase considerably the amount of Msx-expressing mesenchymal cells which are normally recruited from the somite to form the spinous process of the vertebra. Later on, the dorsal part of the vertebra is enlarged, resulting in vertebral fusion and, in some cases (e.g. grafts made at E3), in the formation of a 'giant' spinous process-like structure dorsally. In strong contrast, BMP-producing cells grafted laterally to the neural tube at E2 exerted a negative effect on the expression of Pax1 and Pax3 genes in the somitic mesenchyme, which then turned on Msx genes. Moreover, sclerotomal cell growth and differentiation into cartilage were then inhibited. Dorsalization of the neural tube, manifested by expression of Msx and Pax3 genes in the basal plate contacting the BMP-producing cells, was also observed. In conclusion, this study demonstrates that differentiation of the ventrolateral and dorsal parts of the vertebral cartilage is controlled by different molecular mechanisms. The former develops under the influence of signals arising from the floor plate-notochord complex. These signals inhibit the development of dorsal subcutaneous cartilage forming the spinous process, which requires the influence of BMP4 to differentiate.
The presentation of flowers on a modified stem, the inflorescence, requires the integration of several aspects of meristem behaviour. In Antirrhinum, the inflorescence can be distinguished by its flowers, hairy stem, modified leaves, short internodes and spiral phyllotaxy. We show, by a combination of physiological, genetical and morphological analysis, that the various aspects of the inflorescence are controlled by three pathways. The first pathway, depends on expression of the floricaula gene, and is rapidly and discretely induced by exposure to long daylength. Activation of this pathway occurs in very young axillary meristems, resulting in a floral identity. In addition, the length of subtending leaves and hairiness of the stem are partially modified. The second pathway affects leaf size, internode length, and stem hairiness, but does not confer floral meristem identity. This pathway is induced by long daylength, but not as rapidly or discretely as the floricaula-dependent pathway. The third pathway controls the switch in phyllotaxy from decussate to spiral and is activated independently of daylength. The coordination of these three programmes ensures that apical and axillary meristem behaviour is integrated.
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Escherichia coli seryl-tRNA synthetase (SerRS) is a homo-dimeric class II aminoacyl-tRNA synthetase. Each subunit is composed of two distinct domains: the N-terminal domain is a 60 A long, arm-like coiled coil structure built up of two antiparallel alpha-helices, whereas the C-terminal domain, the catalytic core, is an alpha-beta structure overlying a seven-stranded antiparallel beta-sheet. Deletion of the arm-like domain (SerRS delta 35-97) does not affect the amino acid activation step of the reaction, but reduces aminoacylation activity by more than three orders of magnitude. In the present study, it was shown that the formation of heterodimers from two aminoacylation defective homodimers, the N-terminal deletion and an active site mutant (SerRS E355Q), restored charging activity. The aminoacylation activity in a mixture containing the heterodimers was compared to that of solutions containing the same concentrations of homodimer. The activity of the mixture was eight times higher than the activities of the homodimer solutions, and reached 50% of the theoretical value that would be expected if 50% of the mixture was in the heterodimer form and assuming that a heterodimer contains only one active site. These results are in full agreement with the structural analysis of E. coli SerRS complexed with its cognate tRNA and provide functional evidence for the cross-dimer binding of tRNA in solution.
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We investigated whether exposure of naive and in vitro pre-activated T cells to CD4 monoclonal antibodies (mAb) could induce specific hyporesponsiveness to a subsequent challenge in the absence of CD4 mAb. Unfractionated peripheral blood mononuclear cells were cultured with mitomycin-treated B cell lines as stimulator cells, in the presence or absence of CD4 mAb, then challenged with the same or unrelated stimulator cells. The kinetics of [3H] thymidine incorporation, blast transformation and CD25 expression were determined. Cells activated in primary or secondary culture in the presence of CD4 mAb demonstrated a markedly decreased response to subsequent challenge in the absence of antibody. This effect was reproduced with three different CD4 mAb of the IgG1 and IgG2a subclasses, which recognize two distinct epitopes of the CD4 molecule. Addition of recombinant interleukin-2 (rIL-2) during exposure to CD4 mAb failed to prevent the induction of specific hyporesponsiveness. Similarly, exogenous rIL-2, added together with stimulating cells, failed to restore the specific proliferative response, indicating that the mechanisms were different from those of classical anergy. The hyporesponsiveness was clonally restricted since CD4 mAb-pretreated cells developed a normal primary response to third-party stimulator cells. No increase in the percentage of apoptotic cells was observed in hyporesponsive cell populations, but selective clonal deletion cannot be excluded. The data demonstrate a delayed effect of CD4 ligation on T cell responses to a subsequent challenge.
Mixed membrane preparations from the coleoptiles and first leaves of young barley (Hordeum vulgare L. cv. Triumph) plants catalysed the synthesis of 55% methanol-insoluble labelled material from UDP-[U-14C]glucose, the main components of which were identified as (1,3)(1,4)-beta- and (1,3)-beta-D-glucans. The membrane preparations also catalysed the transformation of UDP-glucose into labelled low-molecular-weight products, mainly glucose (by phosphatase action), glucose-1-phosphate (by phosphodiesterase action) and glyco(phospho)lipids (by glycosyltransferase action). The formation of (1,3)(1,4)-beta-glucans, (1,3)-beta-glucans, and the other reactions competing for UDP-glucose, were monitored simultaneously and quantitatively by a novel procedure based on enzymatic analysis, thin-layer chromatography and digital autoradiography. Thus it was possible (i) to optimise conditions to obtain (1,3)(1,4)-beta-glucan synthesis or (1,3)-beta-glucan synthesis in isolation, and (ii) to study the influence of temperature, pH, cofactors, substrate concentration etc. on the (1,3)(1,4)- and (1,3)-beta-glucan synthesis reactions even when both occurred together. The synthesis of both beta-glucans was optimal at 20 degrees C. In Tris-HCl buffer, the pH optima for (1,3)(1,4)-beta-glucan synthesis and (1,3)-beta-glucan synthesis were pH 8.5 and pH 7.0, respectively. Both glucan-synthesis reactions required Mg2+: (1,3)-beta-glucan synthesis was optimal at 2 mM, whereas (1,3)(1,4)-beta-glucan synthesis continued to increase up to 200 mM Mg2+, when the ion was supplied as the sulphate. (1,3)-beta-Glucan synthesis was Ca2+ dependent and this dependence could be abolished by proteinase treatment.(ABSTRACT TRUNCATED AT 250 WORDS)