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Biomedical subjects

C Rodriguez

Publications and source records attributed to C Rodriguez.

At least 127 records · Page 7Linked to original sources
PubMed1996

HIV disease in children is associated with a selective decrease in CD23+ and CD62L+ B cells.

We characterized the surface phenotype of B cells from HIV+ children in order to better understand the biology of B cell dysregulation. Twenty-nine HIV-infected, twenty-one exposed, and nineteen age-matched control children were studied for expression of CD5, CD10, CD21, CD23, CD25, CD62L, CD71, and CD69. We conclude that, despite persistent high immunoglobulin levels, total B cells decreased as HIV disease progressed, with selective decreases in CD62L+ and CD23+ B cells. This resulted in an increased proportion of usually minor subpopulations of CD62L- and CD23-negative B cells. We did not find significantly altered B cell expression of other activation/immaturity antigens. This suggests an absolute decrease in a subset of antigen-responsive B cells and a disproportionate increase in a subset of hyperstimulated B cells. These findings provide a biological basis for the paradoxical generalized B cell hyperactivity and specific immune unresponsiveness that are characteristic of HIV infection in children.

Antigens, CD↗
PubMed1996

DNA amplifications at 20q13 and MDM2 define distinct subsets of evolved breast and ovarian tumours.

DNA amplification seems to be particularly frequent in human breast tumours and has been associated with cancer evolution and aggressiveness. Recent data indicate that new events should be added to the list, such as the amplifications at chromosome 20q13 or the MDM2 gene. The present work aimed at determining the incidence and clinicopathological signification of these amplifications in a large series of breast and ovarian tumours. We tested 1371 breast and 179 ovarian tumours by Southern blotting and observed amplification of 20q13 in 5.4% breast and 2.8% ovarian carcinomas, whereas MDM2 was found amplified in 5.3% and 3.8% of breast and ovarian tumours respectively. MDM2 RNA expression levels were analysed in a subset of 57 breast tumours and overexpression was observed in 4/57 (7%) of the tumours. Elevated expression levels coincided with amplification of the gene. In breast cancer, 20q13 and MDM2 amplifications seem to define subsets of aggressive tumours. Indeed, 20q13 was correlated to axillary nodal involvement and occurred preferentially in younger patients (< 50 years). Furthermore, 20q13 correlated, as did MDM2 amplification, to aneuploidy. In parallel, we had also tested our tumour DNAs for amplification of CCND1, ERBB-2 and MYC, which made it possible to test for correlations with 20q13 or MDM2 amplifications. Whereas 20q13 showed a very strong correlation to CCND1 amplification, that of MDM2 was prevalent in MYC-amplified tumours. Interestingly, 20q13 and MDM2 amplifications showed some degree of correlation to each other, which may possibly be owing to the fact that both events occurred preferentially in aneuploid tumours. In ovarian cancer, no statistically significant correlation was observed. However, 20q13 amplification occurred preferentially in stage 3 tumours and MDM2 was correlated to ERBB-2 amplification. This may suggest that in ovarian tumours also, 20q13 and MDM2 amplifications occur in late or aggressive cancers.

Breast Neoplasms↗
PubMed1996

Involvement of FGF-8 in initiation, outgrowth and patterning of the vertebrate limb.

Fibroblast Growth Factors (FGFs) are signaling molecules that are important in patterning and growth control during vertebrate limb development. Beads soaked in FGF-1, FGF-2 and FGF-4 are able to induce additional limbs when applied to the flank of young chick embryos (Cohn, M.J., Izpisua-Belmonte, J-C., Abud, H., Heath, J. K., Tickle, C. (1995) Cell 80, 739-746). However, biochemical and expression studies suggest that none of these FGFs is the endogenous signal that initiates limb development. During chick limb development, Fgf-8 transcripts are detected in the intermediate mesoderm and subsequently in the prelimb field ectoderm prior to the formation of the apical ectodermal ridge, structures required for limb initiation and outgrowth, respectively. Later on, Fgf-8 expression is restricted to the ridge cells and expression disappears when the ridge regresses. Application of FGF-8 protein to the flank induces the development of additional limbs. Moreover, we show that FGF-8 can replace the apical ectodermal ridge to maintain Shh expression and outgrowth and patterning of the developing chick limb. Furthermore, continuous and widespread misexpression of FGF-8 causes limb truncations and skeletal alterations with phocomelic or achondroplasia phenotype. Thus, FGF-8 appears to be a key signal involved in initiation, outgrowth and patterning of the developing vertebrate limb.

Amino Acid Sequence↗
PubMed1996

The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions.

We have analyzed the pattern of expression of several genes implicated in limb initiation and outgrowth using limbless chicken embryos. We demonstrate that the expressions of the apical ridge associated genes, Fgf-8, Fgf-4, Bmp-2 and Bmp-4, are undetectable in limbless limb bud ectoderm; however, FGF2 protein is present in the limb bud ectoderm. Shh expression is undetectable in limbless limb bud mesoderm. Nevertheless, limbless limb bud mesoderm shows polarization manifested by the asymmetric expression of Hoxd-11, -12 and -13, Wnt-5a and Bmp-4 genes. The posterior limbless limb bud mesoderm, although not actually expressing Shh, is competent to express it if supplied with exogenous FGF or transplanted to a normal apical ridge environment, providing further evidence of mesodermal asymmetry. Exogenous FGF applied to limbless limb buds permits further growth and determination of recognizable skeletal elements, without the development of an apical ridge. However, the cells competent to express Shh do so at reduced levels; nevertheless, Bmp-2 is then rapidly expressed in the posterior limbless mesoderm. limbless limb buds appear as bi-dorsal structures, as the entire limb bud ectoderm expresses Wnt-7a, a marker for dorsal limb bud ectoderm; the ectoderm fails to express En-1, a marker of ventral ectoderm. As expected, C-Lmx1, which is downstream of Wnt-7a, is expressed in the entire limbless limb bud mesoderm. We conclude that anteroposterior polarity is established in the initial limb bud prior to Shh expression, apical ridge gene expression or dorsal-ventral asymmetry. We propose that the initial pattern of gene expressions in the emergent limb bud is established by axial influences on the limb field. These permit the bud to emerge with asymmetric gene expression before Shh and the apical ridge appear. We report that expression of Fgf-8 by the limb ectoderm is not required for the initiation of the limb bud. The gene expressions in the pre-ridge limb bud mesoderm, as in the limb bud itself, are unstable without stimulation from the apical ridge and the polarizing region (Shh) after budding is initiated. We propose that the defect in limbless limb buds is the lack of a dorsal-ventral interface in the limb bud ectoderm where the apical ridge induction signal would be received and an apical ridge formed. These observations provide evidence for the hypothesis that the dorsal-ventral ectoderm interface is a precondition for apical ridge formation.

Animals↗
PubMed1996

Genetic parameters and trends for milk production of blond-faced Latxa sheep using Bayesian analysis.

The genetic progress attained with the breeding scheme of the blond-faced Latxa dairy sheep in the Spanish Basque Country was assessed by a Bayesian approach based on the marginal posterior distributions of parameters achieved via Gibbs sampling. The data file included 49,056 milk yield records of 22,363 ewes. Normal distributions were assumed for EBV and fixed effects, and scaled inverted chi-square distributions were assumed for variance components or additive, permanent environment, and residual effects. Under vague priors for variance components, the posterior means (SD) for heritability and permanent environment coefficient for milk yield at 120 d were 0.22(0.01) and 0.20(0.01). An important effect on the milk yield (41.6% of the mean) was evident for a genetic group of imported rams. Selection was effective for sheep that were bred by AI and that had known parents. The robustness of results for effect of genetic group and genetic trends was validated using a mildly informative prior constructed from variance components estimated with the related black-faced Latxa breed.

Animals↗
PubMed1996

[Evaluation of a Dot ELISA for the detection of a Rotavirus antigen].

An evaluation of a Dot ELISA made by the Center of Genetic Engineering and Biotechnology for detecting Rotavirus antigen, was carried out. 100 feces samples were analyzed by this technique and the results were compared with those obtained with polyacrylamide gel electrophoresis, technique traditionally used in the Rotavirus diagnosis. It was obtained a high coincidence, specificity and sensitivity among them.

Antigens, Viral↗
PubMed1995

Dorsal cell fate specified by chick Lmx1 during vertebrate limb development.

The positional cues that govern the fate of cells along the dorsoventral axis of the developing vertebrate limb are established in the mesoderm before outgrowth of limb buds. In Drosophila, a LIM/-homeodomain gene, apterous, expressed in the dorsal compartment of the wing disc, specifies dorsal cell fate. Here we report the isolation of a vertebrate LIM-homeodomain containing gene, Chick Lmx1 (C-Lmx1). Transcripts for C-Lmx1 are detected in the presumptive dorsal limb mesoderm and are restricted thereafter to the dorsal mesoderm of the developing chick bud. C-Lmx1 expression is regulated by the overlying ectoderm where Wnt7a messenger RNA is localized. Wnt7a, required for normal development of the dorsoventral axis in mouse limbs, can induce ectopic expression of C-Lmx1 in ventral mesoderm. Misexpression of C-Lmx1 during limb outgrowth causes ventral to dorsal transformations of limb mesoderm. We propose that C-Lmx1 specifies dorsal cell fate during chick limb development.

Animals↗
PubMed1995

CD44 expression patterns in breast and colon tumors: a PCR-based study of splice variants.

CD44 cell-surface receptor expresses multiple isoforms, some of which are believed to play a role in tumor growth and metastasis. The CD44 gene is composed of 19 exons, of which 9 (exons 6 to 14) are alternatively spliced to form inclusions in the intervening membrane proximal region. Sequences present in the shortest metastatic variant cloned from a rat metastatic cell line have been shown to correspond to human exons 10 and 11, also called exons v6 and v7. Using RT-PCR, we have addressed in detail the CD44 isoforms produced in human breast and colon tumors. We analyzed 53 breast-tumor- and 58 colon-tumor-related samples as well as 1 benign mastopathy, 1 normal breast, 4 non-invaded lymph nodes and 8 normal colon tissues. All tumors analyzed expressed the hemopoietic CD44 (CD44H) isoform (no alternatively spliced exons added), whereas 81% expressed the CD44E form (addition exons 12, 13 and 14). Furthermore, 85% of tumors presented complex patterns of expression, with an average number of 5 to 6 bands detected. In view of their implication in the metastatic process, we investigated in greater detail the isoforms containing exons 10 and 11 (v6 and v7). Exon 10 was more frequently expressed than exon 11, 80% and 57% of the samples respectively. The great majority of cases showed ladder-like patterns starting from the shortest forms (exons 5-10 or 5-10-11) and larger-molecular-weight bands corresponding predominantly to sequential inclusions of exons from 3' to 5'. Exon-10 and exon-11 variants were also found in one benign mastopathy. The majority of normal tissues (1 breast and 6/8 colon) expressed only the CD44H isoform. These data indicate that expression of metastatic variants is common in human breast and colon tumors and can occur early during cancer progression, as testified by their presence in a benign breast tumor. While expression of exon-10 variants were correlated with presence of distal metastases in colon tumors, exon-11 variants were not (metastatic events were too rare in our breast-tumor series to reach significance). This suggest that exon 10 may correspond to the minimal sequences required to favor metastatic events.

Alternative Splicing↗
PubMed1995

Cooperative binding of transforming growth factor (TGF)-beta 2 to the types I and II TGF-beta receptors.

TGF-beta 1 binds with high affinity (KD = 25-50 pM) directly to the TGF-beta type II receptor serine-threonine kinase (T beta-RII) in the absence of expression of the TGF-beta type I or III receptors (T beta-RI and T beta-RIII). The serine-threonine kinase T beta-RI is essential for TGF-beta 1 signaling but not for binding to T beta-RII. TGF-beta 2, in contrast, does not bind directly to T beta-RII, although coexpression of T beta-RIII does allow binding and cross-linking of TGF-beta 2 to T beta-RII. Here we show that in transfected COS cells binding and cross-linking of 125I-TGF-beta 2 to T beta-RI or T beta-RII requires expression of both receptors. In cells transfected with the c-myc-tagged human T beta-RII cDNA, only low amounts of 125I-TGF-beta 2 cross-linked to T beta-RI and T beta-RII were detected even with high concentrations (700 pM) of ligand. Cotransfection of the influenza-hemagglutinin-tagged human T beta-RI cDNA dramatically increased the binding of TGF-beta 2 to T beta-RII; the concentration of 125I-TGF-beta 2 required for half-maximal binding and cross-linking to T beta-RI and T beta-RII was approximately 40 pM. Coimmunoprecipitation studies showed that the high affinity receptor for TGF-beta 2 is composed of a hetero-oligomer of T beta-RI and T beta-RII. Thus TGF-beta 1 and -beta 2 bind to TGF-beta receptors in different ways; TGF-beta 1 binds directly to T beta-RII, while binding of TGF-beta 2 to T beta-RII requires coexpression of T beta-RI or T beta-RIII.

Activin Receptors, Type I↗
PubMed1995

Estrogen replacement therapy and fatal ovarian cancer.

The authors examined the relation between use of estrogen replacement therapy and ovarian cancer mortality in a large prospective mortality study of 240,073 peri- and postmenopausal women, none of whom had a prior history of cancer, hysterectomy, or ovarian surgery at enrollment in 1982. During 7 years of follow-up, 436 deaths from ovarian cancer occurred. Cox proportional hazard regression was used to adjust for other risk factors. Ever use of estrogen replacement therapy was associated with a rate ratio for fatal ovarian cancer of 1.15 (95% confidence interval (CI) 0.94-1.42). The mortality rate ratio increased with duration of use prior to entry to this study to 1.40 (95 CI% 0.92-2.11) with 6-10 years of use and 1.71 (95% CI 1.06-2.77) with > or = 11 years of use. The increase in mortality associated with > or = 6 years of use was observed in both current users (rate ratio (RR) = 1.72, 95% CI 1.01-2.90) and former users at study entry (RR = 1.48, 95% CI 0.99-2.22), relative to never users. Risk associated with use was not modified by any of the other risk factors. These data suggest that long-term use of estrogen replacement therapy may increase the risk of fatal ovarian cancer.

Adult↗
PubMed1995

Interleukin-10 is a proliferation factor but not a differentiation factor for human myeloma cells.

Because interleukin-10 (IL-10) is a potent differentiation factor of human B cells into mature plasma cells, we investigated its effect on human malignant plasma cells. IL-10 did not induce any differentiation and increase in Ig synthesis in four human IL-6-dependent malignant plasma cell lines. However, it stimulated the proliferation of two of four cytokine-dependent cell lines in the absence of IL-6 and IL-10-dependent myeloma cell lines have been obtained. The myeloma cell growth activity of IL-10 was unaffected by anti-IL-6 and anti-IL-6R antibodies. Similarly, IL-10 stimulated (P = .001) the proliferation of freshly-explanted myeloma cells in IL-6-deprived cultures of tumor samples from patients with active multiple myeloma (MM) and produced twice as many myeloma cells in these cultures. Again, this cytokine was unable to induce further differentiation (assessed by rate of Ig production) of fresh myeloma cells. A very sensitive enzyme-linked immunosorbent assay (ELISA; 1 pg/mL) only rarely detected IL-10 in the sera of MM patients (3 of 89). On the contrary, serum IL-10 was detected in 60% of patients with plasma cell leukemia (12 of 20). These data show that IL-10 is an IL-6-unrelated growth factor for malignant plasmablastic cells. This cytokine could be involved in the late phase of MM in vivo.

Cell Differentiation↗
PubMed1995

Enhanced susceptibility of cholesteryl sulfate-enriched low density lipoproteins to copper-mediated oxidation.

Cholesteryl sulfate (CS) is a minor component of cell membranes, also present in lipoproteins, and its exact function is unknown. Since oxidation of low density lipoproteins (LDL) is thought to be an important determinant of atherogenesis, we investigated the influence of CS enrichment on copper-mediated oxidation of LDL. CS was found to act as a pro-oxidant, as measured by lipid oxidation parameters. The results also suggest that these effects were dependent on the sulfate group since pure cholesterol or cholesteryl acetate did not promote Cu(2+)-mediated oxidation. Our findings imply that CS may affect the oxidizability and hence the potential atherogenicity of LDL.

Arteriosclerosis↗
PubMed1995

Pro-oxidant effects of 7-hydroperoxycholest-5-en-3 beta-ol on the copper-initiated oxidation of low density lipoprotein.

In low density lipoproteins (LDL) supplemented with aged cholesterol and oxidized in the presence of Cu2+, an increase of the lipid oxidation parameters was observed compared with pure cholesterol-enriched LDL. A compound, identified as 7-hydroperoxycholesterol (7HPC), isolated from aged cholesterol and added to LDL, reproduced the above effects. The results indicate that the pro-oxidant effect of 7HPC is dependent on the hydroperoxy group since the corresponding alcohol derivative, 7 alpha-hydroxycholesterol, had no such effect. These data suggest that among the LDL-associated lipid peroxides, cholesterol peroxides may have important implications in the susceptibility of this lipoprotein to oxidation.

Cholesterol↗
PubMed1995

Expression of genes encoding bone morphogenetic proteins and sonic hedgehog in talpid (ta3) limb buds: their relationships in the signalling cascade involved in limb patterning.

The chicken mutant talpid3 (ta3) has polydactylous limbs with up to 7-8 morphologically similar digits. This lack of antero-posterior polarity in digit pattern is correlated with symmetrical expression of genes of the HoxD complex. We determined the distribution of polarizing activity in limb buds of the chick mutant ta3 by assessing the ability of mesenchyme from various positions along the antero-posterior axis to induce digit duplications when grafted anteriorly into a normal limb. Cells with highest polarizing activity were found at the posterior margin of the wing as in the polarizing region of normal limb buds. However, in contrast to normal limb buds, ta3 anterior mesenchyme also had low polarizing activity. Application of retinoic acid or a polarizing region graft to the anterior of ta3 limb buds changed digit morphology but did not induce digit duplications or digits with any characteristic a-p pattern. To determine which genes are associated with polarizing activity and which are associated with patterning of the digits, we examined expression of the genes Sonic hedgehog (shh), Bmp-2, and Bmp-7, whose expression is normally confined to the posterior margin of the early wing bud and is associated with the polarizing region. In addition, we determined the distribution of Fgf-4 transcripts which in normal limb buds are restricted to the posterior part of the apical ectodermal ridge. In ta3 limb buds, shh expression is restricted to the posterior limb mesenchyme, which has high polarizing activity, but is not expressed in regions which have low polarizing activity. In contrast, Bmp-2 and Bmp-7 are expressed uniformly along the a-p axis. Fgf-4 transcripts are present throughout the apical ectodermal ridge in ta3 limb buds. In the ta3 mutant, there is both an abnormal distribution of signalling activity and response to polarizing signals. In addition, the dissociation between the expression of shh and Bmps suggests distinct roles for the encoded molecules in signalling and response in a-p patterning of limb buds.

Animals↗
PubMed1995

The immunodetected yeast purine-cytosine permease is not N-linked glycosylated, nor are glycosylation sequences required to have a functional permease.

The purine-cytosine permease (PCP) of the yeast Saccharomyces cerevisiae was detected by immunological methods. Using antibodies directed against synthetic peptides, whose sequences were derived from the primary structure of the PCP, immunoprecipitation of [35S]methionine-labelled PCP was achieved either from cellular extracts or from in vitro translation mixtures. Non-labelled PCP was also detected on Western blots of membrane proteins. Similar migration rates were observed for PCP originating both from immunoprecipitated cellular extracts and from in vitro translation mixtures. Hence, post-translational processing, if any, only slightly affects the size of the protein. Also no evidence was found for N-linked core-glycosylation: identical migration rates were observed when immunoprecipitated PCP molecules were extracted from cells labelled for 10 min with [35S]methionine, pretreated or not with tunicamycin. On the other hand, the suppression of the two potential N-linked glycosylation sequences in the DNA did not lead to inactivation of the transport activity, confirming that N-linked glycosylation is not required for the permease activity.

Amino Acid Sequence↗
PubMed1995

Spontaneous abortion and risk of fatal breast cancer in a prospective cohort of United States women.

Controversy exists over the possible relationship between induced and spontaneous abortion and risk of breast cancer. Thus, the association of fatal breast cancer and spontaneous abortion was examined in a large prospective study of United States adult women. After seven years of follow-up, 1,247 cases of fatal breast cancer were observed among 579,274 women who were cancer-free at interview in 1982 and who provided complete reproductive histories. Results from Cox proportional hazards models, adjusted for other risk factors, showed no association between a history of spontaneous abortion and risk of fatal breast cancer (rate ratio [RR] = 0.89, 95 percent confidence interval [CI] = 0.78-1.02). The RR did not increase with increasing numbers of abortions. Parous women who had a spontaneous abortion before their first term birth were not at increased risk compared with parous women with no history of spontaneous abortion (RR = 0.76, CI = 0.54-1.05). Women whose only pregnancy ended in a spontaneous abortion were not at increased risk compared with women who were never pregnant (RR = 0.61, CI = 0.27-1.38) or whose only pregnancy ended in a livebirth (RR = 0.72, CI = 0.32-1.65). These findings do not support an association between spontaneous abortion and fatal breast cancer.

Abortion, Spontaneous↗
PubMed1995

An adaptive chromosomal polymorphism affecting size-related traits, and longevity selection in a natural population of Drosophila buzzatii.

Size-related phenotypic variation among second-chromosome karyotypes in Drosophila buzzatii was examined in an Argentinian natural population. For all measured traits (thorax and wing length; wing, head and face width), this inversion polymorphism exhibited a significant and (additive) linear contribution to the phenotypic variance in newly emerged wild flies. The results suggest that only overall body size, and not body shape, is affected, as no karyotypic variation was found for any trait when the effects of differences in within-karyotype size were removed with Burnaby's method. Likewise, in an experiment of longevity selection in the wild, variation in chromosomal frequencies was verified in the direction predicted on the basis of: (i) previous studies on longevity selection for body size in the wild and (ii) the pattern of chromosomal effects we observed on size. The direction of such selection is consistent with a pattern of antagonistic selection detected in previous studies on the inversion polymorphism.

Age Factors↗