Biomedical subjects

H Araujo

Publications and source records attributed to H Araujo.

8 recordsLinked to original sources

PubMed2006

Graded maternal short gastrulation protein contributes to embryonic dorsal-ventral patterning by delayed induction.

Establishment of the dorsal-ventral (DV) axis of the Drosophila embryo depends on ventral activation of the maternal Toll pathway, which creates a gradient of the NFkB/c-rel-related transcription factor dorsal. Signaling through the maternal BMP pathway also alters the dorsal gradient, probably by regulating degradation of the IkB homologue Cactus. The BMP4 homologue decapentaplegic (dpp) and the BMP antagonist short gastrulation (sog) are expressed by follicle cells during mid-oogenesis, but it is unknown how they affect embryonic patterning following fertilization. Here, we provide evidence that maternal Sog and Dpp proteins are secreted into the perivitelline space where they remain until early embryogenesis to modulate Cactus degradation, enabling their dual function in patterning the eggshell and embryo. We find that metalloproteases encoded by tolloid (tld) and tolkin (tok), which cleave Sog, are expressed by follicle cells and are required to generate DV asymmetry in the Dpp signal. Expression of tld and tok is ventrally restricted by the TGF-alpha ligand encoded by gurken, suggesting that signaling via the EGF receptor pathway may regulate embryonic patterning through two independent mechanisms: by restricting the expression of pipe and thereby activation of Toll signaling and by spatially regulating BMP activity.

Animals↗

PubMed2000

sog and dpp exert opposing maternal functions to modify toll signaling and pattern the dorsoventral axis of the Drosophila embryo.

The short gastrulation (sog) and decapentaplegic (dpp) genes function antagonistically in the early Drosophila zygote to pattern the dorsoventral (DV) axis of the embryo. This interplay between sog and dpp determines the extent of the neuroectoderm and subdivides the dorsal ectoderm into two territories. Here, we present evidence that sog and dpp also play opposing roles during oogenesis in patterning the DV axis of the embryo. We show that maternally produced Dpp increases levels of the I(kappa)B-related protein Cactus and reduces the magnitude of the nuclear concentration gradient of the NF(kappa)B-related Dorsal protein, and that Sog limits this effect. We present evidence suggesting that Dpp signaling increases Cactus levels by reducing a signal-independent component of Cactus degradation. Epistasis experiments reveal that sog and dpp act downstream of, or in parallel to, the Toll receptor to reduce translocation of Dorsal protein into the nucleus. These results broaden the role previously defined for sog and dpp in establishing the embryonic DV axis and reveal a novel form of crossregulation between the NF(kappa)B and TGF(beta) signaling pathways in pattern formation.

Animals↗

PubMed1998

Congenital neuroblastoma in a boy born to a woman with bipolar disorder treated with carbamazepine during pregnancy.

1. A metastatic neuroblastoma was detected immediately after birth in a boy born to a 26 year old woman with bipolar disorder, who received carbamazepine (400 mg/day) all through her pregnancy. The primary tumor was probably located in the adrenal gland of the right side, and multiple metastatic lesions were detected in the skin. 2. In this report the authors review the literature about the side effects teratogenic and carcinogenic effects of carbamazepine, the epidemiology and evolution of the neuroblastoma, and the current scientific opinion about the pharmacological treatment of the pregnant with mood disorders. 3. A causal relationship between the use of carbamazepine and the neuroblastoma development in the present case can not be established; however, as the carcinogenic and teratogenic effects of the drug have been basically assessed in epileptic women, our aim is to alert the medical community in order to conduct further research in psychiatric patients.

Abnormalities, Drug-Induced↗

PubMed1997

Blockage of 9-O-acetyl gangliosides induces microtubule depolymerization in growth cones and neurites.

Gangliosides have been implicated in numerous cellular functions in the developing nervous system. The expression of 9-O-acetyl gangliosides recognized by the JONES mAb correlates with periods of cell migration and axonal pathfinding. In vitro, addition of JONES induces growth cone collapse of dorsal root ganglion neurons. This suggests a modulatory activity of 9-O-acetyl gangliosides on growth cone motility and/or adhesion. In this study we have investigated the effect of JONES mAb addition on the cytoskeleton of dorsal root ganglion neurons in vitro. We have shown that blockage of 9-O-acetyl gangliosides induces the appearance of lateral spikes along the neurites in addition to the effect on the growth cone. Microfilament and microtubular rearrangements accompany these structural modifications. We present evidence that the main effect of JONES mAb is to induce microtubule depolymerization both in growth cones and neurites. Together with the analysis on the spatial distribution of these gangliosides along the cell surface, our results suggest that 9-O-acetyl gangliosides recognized by JONES mAb might serve a concerted action, modulating growth cone motility and axonal branch formation.

Acetylation↗

PubMed1996

Cellular crossreactivity. Implications for solid organ transplantation matching.

This study evaluates the cellular crossreactivity among DR11, DR13, and DR8 molecules using TLC reagents generated in reciprocal priming combinations where the responder and stimulator cells express different microvariants of DR11. The large majority of T lymphocyte clones (TLC) derived from such stimulation detect not only the product of the specific DR11 allele expressed by the stimulator but also detect subsets of DR molecules that span serologic specificities. Thus, TLC generated in response to DR(alpha,beta1*1102) detect DR(alpha,beta1*1103) and products of specific DR13, DR8, DR2 and DR4 alleles. Whereas, TLC generated in response to DR(alpha,beta1*1104) detect DR(alpha,beta1*1101), DR(alpha,beta1*1103), and products encoded by specific DR8 and DR2 but not DR13 or DR4 alleles. Since DR11 microvariants cannot be identified serologically, this type of mismatch certainly occurs frequently between DR11 serologically matched donors and recipients. Particularly affected are populations, such as the African American population, that exhibit extensive HLA diversity and exhibit different frequencies of HLA alleles compared with those of the majority of serologically matched cadaveric donors. Rapid methods of DNA-based HLA typing now makes it feasible to utilize this methodology for allele level identificaiton of recipient and donor alleles. Based on the strength of the alloproliferative responses and on the recognition patterns of the TLC reported here, we suggest that retransplant patients might benefit by excluding subsequent donors expressing DR molecules that in vitro demonstrate strong cellular crossreactivity with DR molecules expressed by the previous donor(s) as well as those DR molecules shared with the previous donor(s). Since such a matching schema has the potential to improve retransplant allograft survival, particularly in patients from minority population groups, it should be evaluated clinically.

Alleles↗

PubMed1993

Characterization of PEA-15, a major substrate for protein kinase C in astrocytes.

Astrocytes in the central nervous system are involved in a variety of functions including storage of glycogen, maintenance of the extracellular ionic equilibrium, and support for the migration and the differentiation of neurons. Astrocytes express membrane receptors allowing them to respond to extracellular signals. Activation of receptors induces a cascade of events, such as stimulation of protein kinases and subsequent phosphorylation of target proteins. To understand the regulatory processes underlying neuroglial interactions, attempts were made to identify major phosphorylated proteins in striatal astrocytes, grown in primary culture and labeled with [32P]phosphate. Two-dimensional gel electrophoresis revealed a major doublet, Pa and Pb, of highly labeled spots, with a low molecular weight (M(r) = 15,000) and acidic pI (pI = 5.2 and 5.3, respectively). Using an enriched, heat-stable, cytosolic fraction, Pa and Pb were eluted from semi-preparative two-dimensional gels and subjected to a limited proteolysis and partial microsequencing. The same sequences were obtained within Pa and Pb and had no homology with other known protein. Antibodies raised against corresponding synthetic peptides confirm that the doublet represents two isoelectric variants of the same protein, which also exists under a nonphosphorylated form, N. We propose to name this protein PEA-15, for Phosphoprotein Enriched in Astrocytes-15 kDa, according to its large enrichment in these cells. Treatment of intact astrocytes with 12-O-tetradecanoylphorbol-13-acetate (TPA), which stimulates protein kinase C (PKC), increased the phosphorylation of the more acidic spot (Pb) while decreasing Pa intensity. Stimulations of astrocytes known to increase PKC activity, i.e. noradrenaline, or its inhibition by decreasing extracellular calcium concentrations, staurosporine, or desensitization following long term treatment with TPA, induced a phosphorylation or a dephosphorylation of PEA-15, respectively. Using purified PKC, PEA-15 appeared to be a good substrate in vitro. Two-dimensional peptide mapping revealed that the phosphorylation site in intact cells was identical with the site phosphorylated by PKC in vitro. Mapping the phosphopeptides by HPLC following endolysine C treatment lead to the identification of a sequence, phosphorylated in intact astrocytes and in vitro by PKC, containing a consensus site for PKC: LTRIPSAKK. Antibodies raised against a synthetic peptide derived from this sequence recognized N and Pa in control conditions and Pb after its dephosphorylation. Thus, PEA-15 is an endogenous substrate for PKC, the kinase mediating the transition from Pa to Pb.

Amino Acid Sequence↗

PubMed1993

[E rosette inhibition in alcoholic liver disease].

Various studies performed in chronic alcoholic patients have demonstrated immunologic alterations, which have been described more often in patients with alcoholic hepatitis or liver cirrhosis. We have observed that the serum of some patients with alcoholic liver cirrhosis produces the inhibition of E rosette formation by T lymphocytes. This observation induced us to study E rosette formation and its probable inhibition by the serum of chronic alcoholic patients. Subjects were split into three groups: Group 1: n = 21. Normal individuals. Group 2: n = 15. Chronic alcoholic patients without cirrhosis. Group 3: n = 26. Chronic alcoholic patients with histologically demonstrated liver cirrhosis. E rosette and E rosette inhibition (TIRE) sera tests were performed utilizing subject's sera tested against lymphocytes of normal individuals not related to group 1. The results found are listed in detail in Table 1 (mean = -SD) and Figure 1 (median), for each of the test groups. We applied unifactorial variance analysis and observed highly significant differences between the groups studied in all tests performed. It was found that tests that utilized I.E. discriminate most efficiently among the three groups of patients and that those which utilize unabsorbed assay serum (S/A) yield the best differentiation. Using this last assay it was observed that 20/21 control individuals showed less than 15% inhibition. On this basis, we decided to separate the results into 15% regular intervals (Table 3). Inhibition above 30% was found only in cirrhotic patients with the exception of one individual of the control group and one non-cirrhotic alcoholic patient with no alcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMedDate not supplied

Chromosomal abnormalities and polymorphisms in infertile men.

The aim of this study was to determine the prevalence of alterations and normal variable chromosome features in males from infertile couples. Karyotyping was performed to 84 men attending the infertility clinic at the Hospital Clinic i Provincial of Barcelona (Spain). Sex chromosome abnormalities were detected in 19 patients (26.62%): 14 (16.67%) aneuploidies 47,XXY and 47,XYY, 3 (3.57%) Y-chromosome long arm deletions; 1 (1.19%) mosaic 45,x/46,XY and 1 (1.19%) Robertsonian translocation (45.X-15-Y+t(15p: Yq). Chromosomal polymorphisms were observed in 29 patients. Yqh+ was the most frequent variant in sex chromosomes and increased length in heterochromatin and satellites were present in autosomal chromosomes. The high prevalence of chromosomal abnormalities observed in infertile men justify the use of karyotyping to evaluate males enrolled in new assisted reproductive technologies programs.

Adult↗