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Biomedical subjects

B Ferreiro

Publications and source records attributed to B Ferreiro.

15 recordsLinked to original sources
PubMed1998

Antimorphic goosecoids.

goosecoid (gsc) is a homeobox gene expressed in the Spemann organizer that has been implicated in vertebrate axis formation. Here antimorphic gscs are described. One antimorphic gsc (MTgsc) was fortuitously created by adding 5 myc epitopes to the N terminus of gsc. The other antimorph (VP16gsc) contains the transcriptional activation domain of VP16. mRNA injection of either antimorph inhibits dorsal gastrulation movements and leads to embryos with severe axial defects. They upregulate ventral gene expression in the dorsal marginal zone and inhibit dorsal mesoderm differentiation. Like the VP16 domain, the N-terminal myc tags act by converting wild-type gsc from a transcriptional repressor into an activator. However, unlike MTgsc, VP16gsc is able at low dose to uncouple head from trunk formation, indicating that different antimorphs may elicit distinct phenotypes. The experiments reveal that gsc and/or gsc-related genes function in axis formation and gastrulation. Moreover, this work warns against using myc tags indiscriminately for labeling DNA-binding proteins.

Animals↗
PubMed1996

[Comparative study of HELISAL T.M. RAPID BLOOD and ELISA, JATROX and pathologic anatomy in the diagnosis of Helicobacter pylori infection].

OBJECTIVES: To assess the usefulness of HELISAL in the diagnosis of Helicobacter pylori infection by comparing it with ELISA, JATROX and histopathologic findings. EXPERIMENTAL DESIGN: Randomized prospective study. PATIENTS: Sixty-one patients, thirty-three males and twenty-eight females, 18-73 years old, submitted to esophagogastroduodenoscopy. RESULTS: The sensitivity of HELISAL when compared to ELISA test was 60.8%, the specificity 73.3%, the positive predictive value 87.5%, the negative predictive value 37.9%, and the kappa index 0.26. When compared to histopathologic test: sensitivity 60.9%, specificity 65%, positive predictive value 78.1%, negative predictive value 44.7%, kappa 0.28. When compared to JATROX, sensitivity 57.7%, specificity 62.5%, positive predictive value 81.2%, negative predictive value 34.4%, kappa 0.21. CONCLUSION: The sensitivity of HELISAL test is lower than that of other compared tests, and the negative predictive value is very low. The specificity and the positive predictive value are higher than the sensitivity. The kappa index shows a very low concordance.

Adult↗
PubMed1995

Fate of the anterior neural ridge and the morphogenesis of the Xenopus forebrain.

The fate of the anterior neural ridge was studied by following the relative movements of simultaneous spot applications of DiI and DiO from stage 15 through stage 45. These dye movements were mapped onto the neuroepithelium of the developing brain whose shape was gleaned from whole-mount in situs to neural cell adhesion molecule and dissections of the developing nervous system. The result is a model of the cell movements that drive the morphogenesis of the forebrain. The midanterior ridge moves inside and drops down along the most anterior wall of the neural tube. It then pushes forward a bit, rotates ventrally during forebrain flexing, and gives rise to the chiasmatic ridge and anterior hypothalamus. The midanterior plate drops, forming the floor of the forebrain ventricle, and, keeping its place behind the ridge, it gives rise to the posterior hypothalamus or infundibulum. The midlateral anterior ridge slides into the lateral anterior wall of the neural tube and stretches laterally into the optic stalk and retina, and then rotates into a ventral position. The lateral anterior ridge converges to the most anterior part of the dorsal midline during neural tube closure, then rotates anteriorly, and gives rise to telencephalic structures. Whole-mount bromodeoxyuridine labeling at these stages showed that cell division is widespread and relatively uniform throughout the brain during the late neurula and early tailbud stages, but that during late tailbud stages cell division becomes restricted to specific proliferative zones. We conclude that the early morphogenesis of the brain is carried out largely by choreographed cell movements and that later morphogenesis depends on spatially restricted patterns of cell division.

Animals↗
PubMed1995

Codependency in nurses. How it affects your organization.

Codependence in a staff nurse affects both direct patient care and relationships with coworkers, physicians, and supervisors. Codependent behaviors negatively impact the nurse's sphere of influence. The nurse manager's codependency has the same impact, but the sphere of influence is larger and thus, the potential for harm is greater. Codependent behaviors enacted at different levels of an organization can disrupt an entire institution or profession. The author describes how nurses' practices are affected by codependent behaviors and identifies ways in which those behaviors can be modified by good management.

Adult↗
PubMed1994

XASH genes promote neurogenesis in Xenopus embryos.

Neural development in Drosophila is promoted by a family of basic helix-loop-helix (bHLH) transcription factors encoded within the Achaete Scute-Complex (AS-C). XASH-3, a Xenopus homolog of the Drosophila AS-C genes, is expressed during neural induction within a portion of the dorsal ectoderm that gives rise to the neural plate and tube. Here, we show that XASH-3, when expressed with the promiscuous binding partner XE12, specifically activates the expression of neural genes in naive ectoderm, suggesting that XASH-3 promotes neural development. Moreover, XASH-3/XE12 RNA injections into embryos lead to hypertrophy of the neural tube. Interestingly, XASH-3 misexpression does not lead to the formation of ectopic neural tissue in ventral regions, suggesting that the domain of XASH proneural function is restricted in the embryo. In contrast to the neural inducer noggin, which permanently activates the NCAM gene, the activation of neural genes by XASH-3/XE12 is not stable in naive ectoderm, yet XASH-3/XE12 powerfully and stably activates NCAM, Neurofilament and type III beta-tubulin gene expression in noggin-treated ectoderm. These results show that the XASH-3 promotes neural development, and suggest that its activity depends on additional factors which are induced in ectoderm by factors such as noggin.

Animals↗
PubMed1993

XASH1, a Xenopus homolog of achaete-scute: a proneural gene in anterior regions of the vertebrate CNS.

The pro-neural achaete-scute complex (ASC) of Drosophila encodes four homologous proteins, each containing a basic helix-loop-helix (bHLH) domain, characteristic of a large family of transcription factors. We have isolated XASH1, a Xenopus homolog of achaete-scute. The XASH1 protein is very similar to the ASC proteins of Drosophila and the rat homolog, MASH1. XASH1 is expressed in the embryonic anterior central nervous system in a dynamic sequence, first in the midbrain, then in the forebrain, and then in the eye and hindbrain. In the larva, XASH1 expression correlates with regions of continued neurogenesis in the CNS, revealing the pattern of rhombomeres in the hindbrain, and other proliferative zones in the eye and midbrain. As a heterodimer with the bHLH protein E12, XASH1 binds specifically to an enhancer sequence derived from the promoter of the proneural achaete gene of Drosophila. This binding is inhibited by the extramacrochaete protein, a negative regulator of ASC gene function and neurogenesis in Drosophila. The combined evidence described in this paper strongly suggests that XASH1 plays a role in Xenopus neurogenesis similar to that played by the ASC genes in Drosophila.

Amino Acid Sequence↗
PubMed1991

Effects of neonatal hypothyroidism on rat brain gene expression.

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.

Animals↗
PubMed1990

Thyroid hormone economy in pregnant rats near term: a "physiological" animal model of nonthyroidal illness?

We have studied the changes in thyroid hormone economy that occur in normal pregnant rats between 17-22 days of gestation. T4 and T3 decreased in all extrathyroidal tissues studied, namely plasma, liver, kidney, lung, heart, and skeletal muscle. The exception is the concentration of T3 in cerebral cortex, which remains unchanged, possibly as a consequence of an increase in type II 5'-iodothyronine deiodinase activity. The marked decrease observed in most T4 and T3 pools was not accompanied by a commensurate increase in circulating TSH levels, which at 21 days gestation were either unchanged or actually decreased. The TSH response to TRH appeared to be prolonged. alpha-Glycerophosphate dehydrogenase activity was decreased in the liver, in accordance with its thyroid hormone deficiency. Hepatic type I 5'-iodothyronine deiodinase activity, however, did not decrease, but was slightly increased. Thus, thyroid hormone economy in the pregnant rat near term shows striking similarities with several (but not all) of the changes described in patients with nonthyroidal illness and in several animal models used to study this condition. It is suggested that attenuation of the negative feedback response to the decrease in thyroid hormone pools, leading to low levels of thyroid hormones in most tissues, is the normal physiological response to situations where preservation of energy (and protein) represents a distinct adaptive advantage, as in the case of the pregnant rat and her conceptus.

Animals↗
PubMed1990

T3 receptor occupancy and T3 levels in plasma and cytosol during rat brain development.

The concentration and occupancy of the thyroid hormone receptor have been measured in rat brain nuclear extracts at the end of the fetal period and during the postnatal period. Receptor occupancy attained maximal values at postnatal day 15 (52% of total receptor binding sites occupied by T3) and correlated with plasma and cytosol total and free T3. The values for these parameters showed greater differences throughout development than did receptor occupancy. From gestational day 21 to postnatal day 15, total T3 increased in plasma from 0.18 to 1 nmol/l and in cytosol from 1 to 7.5 pmol/l. Free T3 increased in plasma from 1.2 to 6 pmol/l and in cytosol from 8 to 59 pmol/l. Nuclear free T3, calculated on the basis of receptor occupancy, and Kd increased in parallel, from 39.8 to 107 pmol/l at the same ages. Values for nuclear free T3 were between 2 and 5 times those in cytosol and between 10 and 40 times those in plasma, suggesting the presence of a small free T3 gradient from plasma to the nucleus. All of the above changes take place during the critical period of oligodendrocyte differentiation and the start of myelin gene expression, suggesting that thyroid hormone influences these important events of brain maturation.

Aging↗
PubMed1988

Preferential saturation of brain 3,5,3'-triiodothyronine receptor during development in fetal lambs.

The concentrations of T4 and T3 were measured in brain, liver, and lung of fetal lambs at 100 days gestational age. The highest concentrations of T4 were found in lung (26.8 ng/g). Brain T4 (8.8 ng/g) was only 30% of lung T4. In contrast, higher concentrations of T3 were found in brain (1.8 ng/g) than in lung (0.39 ng/g) or liver (0.36 ng/g). Nuclear T3 was 16% of the total T3 in brain and 44% of that in lung. The degree of saturation of the nuclear T3 receptor was estimated from the concentrations of nuclear T3 and nuclear receptor. Receptor saturation was low in liver and lung (10%) and high in brain (74%). Receptor occupancy was also measured directly in vitro by comparing the binding of [125I]T3 in nuclear extracts at 0 and 20 C. This method is based on the different rates of dissociation of the T3-receptor complex at these temperatures (0.045 and 0.618 h-1, respectively). Therefore, [125I]T3 was bound mainly to unoccupied sites at 0 C, whereas at 20 C it bound to unoccupied sites plus a fraction (70%) of endogenously occupied sites. There was no difference in binding at the two temperatures using lung extract, reflecting a very low occupancy. Data from brain suggested 61% receptor saturation. Total and free T3 were measured in plasma and in lung and brain cytosols, and the figures were compared to the intranuclear free T3 calculated by the law of mass action, from the affinity and saturation of receptor. In lung, the concentrations of cytosolic (5.4 +/- 1.9 pM) and nuclear (8.6 pM) free T3 were similar to that of plasma T3 (3.7 +/- 0.99 pM). In contrast, brain cytosolic (14.9 +/- 1.2 pM) and nuclear (203 pM) free T3 revealed the presence of free T3 gradients from cytosol to plasma (4-fold) and from nucleus to cytosol (13.6-fold). The data suggest that the sheep brain is a major target of thyroid hormone action at the end of the neuroblast proliferation period. Mechanisms are locally present in the brain at this stage of development to ensure a high saturation of the nuclear T3 receptor.

Animals↗
PubMed1988

Estimation of nuclear thyroid hormone receptor saturation in human fetal brain and lung during early gestation.

The total number and saturation of nuclear receptors for T3 were measured in human fetal brain and lung from the 9th to the 13th week of fetal life. The concentrations of occupied and unoccupied receptor sites were determined by measuring total binding capacity at 0 and 22 C. At 0 C [125I]T3 was bound mainly to unoccupied sites, whereas at 22 C it was bound to unoccupied sites plus a fraction (70%) of endogenously occupied sites. Saturations of brain and lung receptors were similar (12-27%). From the fractional receptor occupancy and the receptor dissociation constants (34 pmol/L in brain and 56 pmol/L in lung) the concentration of intranuclear free T3 was calculated to be 9 pmol/L in brain and 11 pmol/L in lung. Total and free cytosolic T3 were measured by RIA and equilibrium dialysis. Total T3 was below the limit of detection in lung (90 pmol/L). The concentration of free T3 in brain cytosol was 0.95 pmol/L at 11 weeks and 2.96 pmol/L at 13 weeks, i.e. considerably lower than the nuclear free T3 concentration. These results suggest the presence of a small gradient (3-fold) between nuclear and cytosolic free T3 in both fetal tissues. The data strongly support the idea that thyroid hormones influence human brain development at least from the 9th to the 10th week of gestational age.

Brain↗
PubMed1987

Ontogenesis of thyroid hormone receptor in foetal lambs.

Affinity and concentration of T3 receptor sites have been measured in nuclear extracts from the brain, lung, and liver of foetal lamb tissues at 50, 82 and 100 days of gestational age. Control experiments indicated that the concentration of sites was similar when nuclear extracts or purified nuclei were used, and that maximal binding capacity was obtained after 2 h of incubation at 22 degrees C. The pattern of receptor binding affinity when different thyroid hormone analogs were used in competition assays with [125I]T3 was T3 greater than 3,5,3'-triiodothyroacetic acid (Triac) greater than T4 in the lung and brain. In the liver, Triac had the same affinity as T3. The sedimentation coefficient of the receptor was 3.6 S in lung. There were minor changes of receptor affinity in the brain, but not in the lung or liver, during development with the highest value at 82 days. Receptor concentration increased twice from 50 to 82 days. Since in the brain this is the period of neuroblast proliferation, the results suggest that thyroid hormone is required for proper foetal lamb development and, in particular, for neuroblast proliferation and/or differentiation.

Animals↗
PubMed1985

The early ontogenesis of thyroid hormone receptor in the rat fetus.

We have determined the concentration of thyroid hormone receptor binding sites in nuclear extracts derived from rat fetal organs throughout gestation and the postnatal period. Before day 14 of gestation nuclear extracts were obtained from whole fetuses. No receptor binding activity could be detected at day 12 of gestational age, and small amounts were detected at day 13 (maximum binding capacity less than 50 fmol/mg DNA). The receptor could be measured in pools of individual organs from day 14 (brain) or from day 16 (heart, liver, and lung) onwards. The order of analog binding affinity at 14 days was triiodothyroacetic acid = T3 greater than T4 greater than rT3, suggesting that at 14 days of fetal age the receptor has the same binding specificity as the receptor from mature tissues. In brain, the concentration of binding sites increased from 77 fmol/mg DNA at 14 days to 210 fmol/mg DNA at 17 days, remaining at this level until birth. Receptor concentration was identical whether the binding assays were performed on purified nuclei or nuclear extracts. There was no effect of maternofetal hypothyroidism on receptor concentration in the brain at 21 days of gestational age. Lung concentrations of receptor also remained constant during the fetal period. During the postnatal period, there was an increase in receptor concentration in brain and lung, with maximum levels at day 6. The pattern of receptor development in heart and liver was different, since its concentration increased progressively throughout the fetal and postnatal periods towards the levels found in adult rat tissues. The results suggest that the appearance of the thyroid hormone receptor coincides with that of the first fetal thyroid gland structures, but that it occurs much before thyroid function is fully established. As far as the receptor is concerned, fetal tissues have the potential to respond to thyroid hormone as early as the 13th day of gestational age.

Animals↗