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Biomedical subjects

J Urban

Publications and source records attributed to J Urban.

At least 55 records · Page 3Linked to original sources
PubMed1998

GH, IGF-I, IGFBP-3 and IGFBP-2 in cerebrospinal fluid of infants, during puberty and in adults.

During diagnostic lumbar punctions cerbrospinal fluid (CSF) was collected for the determination of GH, IGF-I, IGFBP-3 and IGFBP-2. The patients were 0.3 to 68 years od and suffered from viral infections, leukemias, M. Hodgkin or multiple sclerosis. Only CSF samples without any pathological alterations were analysed. In infants and adults CSF GH concentrations significantly declined with age, while IGF-I and the two binding proteins were unrelated to age. GH was not correlated to IGF-I, IGFBP-3 or IGFBP-2. However, IGF-I was strongly related to IGFBP-3 (r = 0.529; < 0.001) and IGFBP-2 (r = 0.796; < 0.001) as was IGFBP-3 to IGFBP-2 (r = 0.685; < 0.001), suggesting dependence of the three variables. With IGFBP-3 or IGFBP-2 as control variables (partial correlation) IGF-I was no longer related to the binding proteins, while the relation of IGFBP-3 to IGFBP-2 remained unchanged with IGF-I as the control variable (r = 0.687; < 0.001). The results suggest that the age-related decrease of CSF GH may contribute to the age-dependent decline of GH receptors in brain, which are up-regulated by GH. Furthermore, in CSF IGF-I concentrations were determined by the two binding proteins. It may be speculated that the transfer of IGF-I through the blood CSF barrier or its production in brain may be closely related to the IGF-binding proteins.

Adolescent↗
PubMed1998

Gonadotropins regulate inducible cyclic adenosine 3',5'-monophosphate early repressor in the rat ovary: implications for inhibin alpha subunit gene expression.

Many hormones that stimulate intracellular signaling pathways utilizing the second messenger cAMP affect gene expression in target cells through the activation of cAMP-responsive transcriptional regulatory proteins. Two of the best characterized of these are the cAMP-response element (CRE)-binding protein (CREB) and the CRE-modulatory protein (CREM). CREB and CREM are expressed as a family of proteins that have diverse activities in either stimulating or repressing gene transcription. In this study we examined the expression and regulation of the CREM gene in the rat ovary and in granulosa cells, to determine whether repressor isoforms of CREM might have a role in the LH-mediated suppression of inhibin alpha-subunit gene expression that occurs just before ovulation. We found that the predominant CREM mRNAs in the ovary correspond to previously described internal transcripts of the CREM gene that encode the inducible cAMP early repressor (ICER). ICER mRNAs are strongly induced in the ovary by exogenous gonadotropins in immature rats and are transiently expressed in the ovary immediately after the preovulatory LH surge in adult cycling rats. Although ICER is expressed in multiple ovarian cell types, expression in granulosa cells is observed only in response to LH stimulation. ICER mRNAs are also induced by the activation of cAMP-signaling pathways in cultured primary granulosa cells. To determine whether ICER can act as a functional repressor to modulate potential target genes such as the inhibin alpha-subunit gene, an ICER expression construct was transiently co-transfected into a granulosa cell line along with an inhibin alpha-subunit promoter-luciferase reporter gene. Both basal and cAMP-induced expression of the inhibin alpha-subunit promoter were suppressed by ICER. These studies reveal that CREM, a tissue-specific factor, is expressed and regulated by gonadotropins in the ovary, that the predominant CREM transcripts encode the repressor protein ICER, and that ICER is capable of inhibiting cAMP-induced expression of the inhibin alpha-subunit gene. Our findings are consistent with a role for repressors such as ICER in mediating the suppression of inhibin alpha-subunit gene expression that occurs in the ovary at the time of the preovulatory LH surge.

Animals↗
PubMed1998

Differential effects of EGF receptor signalling on neuroblast lineages along the dorsoventral axis of the Drosophila CNS.

The Drosophila ventral nerve cord derives from a stereotype population of about 30 neural stem cells, the neuroblasts, per hemineuromere. Previous experiments provided indications for inductive signals at ventral sites of the neuroectoderm that confer neuroblast identities. Using cell lineage analysis, molecular markers and cell transplantation, we show here that EGF receptor signalling plays an instructive role in CNS patterning and exerts differential effects on dorsoventral subpopulations of neuroblasts. The Drosophila EGF receptor (DER) is capable of cell autonomously specifiying medial and intermediate neuroblast cell fates. DER signalling appears to be most critical for proper development of intermediate neuroblasts and less important for medial neuroblasts. It is not required for lateral neuroblast lineages or for cells to adopt CNS midline cell fate. Thus, dorsoventral patterning of the CNS involves both DER-dependent and -independent regulatory pathways. Furthermore, we discuss the possibility that different phases of DER activation exist during neuroectodermal patterning with an early phase independent of midline-derived signals.

Animals↗
PubMed1998

[Antepartum amniotic fluid index and pregnancy outcome].

Our purpose was to evaluate prognostic value of antepartum amniotic fluid index (AFI) on fetal and newborn outcome, because oligohydramnion is associated with increased risk of fetal and newborn distress. Perinatal outcome was defined by 1' and 5' Apgar score, intrapartum fetal heart rate (FHR), blood gas, acid-base status in umbilical artery, mode of delivery and meconium-stained amniotic fluid. Data was analysed with CSS Statistica for Windows package by test t for independent samples and chi 2. Prospective observations was conducted with 84 singleton pregnancies complicated by oligohydramnion (AFI < or = 5 cm). A 336 pregnant women, with normal amniotic fluid index and no complicated pregnancy, was considered as controls. No increased operative delivery and meconium-stained amniotic fluid rate was noted. There was no significant effects AFI on blood gases in umbilical artery and Apgar score. Oligohydramnion was associated with increased risk of fetal acidosis (pH < 7.16) (p = 0.009) and abnormalities of FHR (variable decelerations) (p = 0.004). Reduced AFI had poor predictive value of fetal acidosis and newborn depression positive predictive value (8-13%). Summarizing the results, our investigation showed that amniotic fluid index is only one point in the prognosis of perinatal outcome.

Adult↗
PubMed1997

The embryonic central nervous system lineages of Drosophila melanogaster. II. Neuroblast lineages derived from the dorsal part of the neuroectoderm.

In Drosophila, central nervous system (CNS) formation starts with the delamination from the neuroectoderm of about 30 neuroblasts (NBs) per hemisegment. They give rise to approximately 350 neurons and 30 glial cells during embryonic development. Understanding the mechanisms leading to cell fate specification and differentiation in the CNS requires the identification of the NB lineages. The embryonic lineages derived from 17 NBs of the ventral part of the neuroectoderm have previously been described (Bossing et al., 1996). Here we present 13 lineages derived from the dorsal part of the neuroectoderm and we assign 12 of them to identified NBs. Together, the 13 lineages comprise approximately 120 neurons and 22 to 27 glial cells which we include in a systematic terminology. Therefore, NBs from the dorsal neuroectoderm produce about 90% of the glial cells in the embryonic ventral ganglion. Two of the NBs give rise to glial progeny exclusively (NB 6-4A, GP) and five to glia as well as neurons (NBs 1-3, 2-5, 5-6, 6-4T, 7-4). These seven NBs are arranged as a group in the most lateral region of the NB layer. The other lineages (NBs 2-4, 3-3, 3-5, 4-3, 4-4, 5-4, clone y) are composed exclusively of neurons (interneurons, motoneurons, or both). Additionally, it has been possible to link the lateral cluster of even-skipped expressing cells (EL) to the lineage of NB 3-3. Along with the previously described clones, the vast majority (more than 90%) of cell lineages in the embryonic ventral nerve cord (thorax, abdomen) are now known. Moreover, previously identified neurons and most glial cells are now linked to certain lineages and, thus, to particular NBs. This complete set of data provides a foundation for the interpretation of mutant phenotypes and for future investigations on cell fate specification and differentiation.

Animals↗
PubMed1997

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds.

HIV-1 and HIV-2 proteinases (PR) are responsible for the processing of viral polyproteins, a step that is crucial for the formation of infectious virus particles. PR represents one of the most important targets for antiviral chemotherapy. Inhibitors of HIV-1 PR usually exhibit a 10- to 100-fold weaker affinity for HIV-2 PR. In order to design subnanomolar inhibitors for both HIV-1 and HIV-2 PRs, we prepared a series of compounds varying in the type of scissile bond replacement as well as in the P1, P1', and P2' side chains. While inhibitors containing reduced amide, hydroxyethylamine and statine isosteres had Ki values in the range of 10(-10)-10(-9) M against HIV-1 PR; their activities against HIV-2 PR were several orders of magnitude lower. Glutamic acid was identified to be the optimal P2' residue for both PRs. HIV-2 PR was shown to be more sensitive to P2' Glu-->Gln replacement. Using this data set we were able to design and prepare hydroxyethylene isostere containing inhibitors that were equipotent against both PRs.

Aspartic Acid Endopeptidases↗
PubMed1997

Cell lineage and cell fate specification in the embryonic CNS of Drosophila.

The Drosophila CNS derives from a population of neural stem cells, called neuroblasts (NBs), which delaminate individually from the neurogenic region of the ectoderm. In the embryonic ventral nerve cord each NB can be uniquely identified and gives rise to a specific lineage consisting of neurons and/or glial cells. This 'NB identity' is dependent on the position of the progenitor cells in the neuroectoderm before delamination. The positional information is provided by the products of segment polarity and dorsoventral (D/V) patterning genes. Subsequently, 'cell fate genes' like huckebein (hkb) and eagle (eg) contribute to the generation of specific NB lineages. These genes act downstream of segment polarity and D/V patterning genes and regulate different processes such as the generation of glial cells and the determination of serotonergic neurons.

Journal Article↗
PubMed1997

GAL4-responsive UAS-tau as a tool for studying the anatomy and development of the Drosophila central nervous system.

To improve the quality of cytoplasmic labelling of GAL4-expressing cells in Drosophila enhancer-trap and transgenic strains, a new GAL4-responsive reporter UAS-tau, which features a bovine tau cDNA under control of a yeast upstream activation sequence (UAS), was tested. Tau, a microtubule-associated protein, is distributed actively and evenly into all cellular processes. Monoclonal anti-bovine Tau antibody reveals the axonal structure of the labelled cells with detail similar to that of Golgi impregnation. We demonstrate that the UAS-tau system is especially useful for studying processes of differentiation and reorganisation of identified neurones during postembryonic development.

Animals↗
PubMed1997

The differentiation of the serotonergic neurons in the Drosophila ventral nerve cord depends on the combined function of the zinc finger proteins Eagle and Huckebein.

The Drosophila ventral nerve cord (vNC) derives from a stereotyped population of neural stem cells, neuroblasts (NBs), each of which gives rise to a characteristic cell lineage. The mechanisms leading to the specification and differentiation of these lineages are largely unknown. Here we analyse mechanisms leading to cell differentiation within the NB 7-3 lineage. Analogous to the grasshopper, NB 7-3 is the progenitor of the Drosophila vNC serotonergic neurons. The zinc finger protein Eagle (Eg) is expressed in NB 7-3 just after delamination and is present in all NB 7-3 progeny until late stage 17. DiI cell lineage tracing and immunocytochemistry reveal that eg is required for normal pathfinding of interneuronal projections and for restricting the cell number in the thoracic NB 7-3 lineage. Moreover, eg is required for serotonin expression. Ectopic expression of Eg protein forces specific additional CNS cells to enter the serotonergic differentiation pathway. Like NB 7-3, the progenitor(s) of these ectopic cells express Huckebein (Hkb), another zinc finger protein. However, their progenitors do not express engrailed (en) as opposed to the NB 7-3 lineage, where en acts upstream of eg. We conclude that eg and hkb act in concert to determine serotonergic cell fate, while en is more distantly involved in this process by activating eg expression. Thus, we provide the first functional evidence for a combinatorial code of transcription factors acting early but downstream of segment polarity genes to specify a unique neuronal cell fate.

Abdomen↗
PubMed1997

Induction of identified mesodermal cells by CNS midline progenitors in Drosophila.

The Drosophila ventral midline cells generate a discrete set of CNS lineages, required for proper patterning of the ventral ectoderm. Here we provide the first evidence that the CNS midline cells also exert inductive effects on the mesoderm. Mesodermal progenitors adjacent to the midline progenitor cells give rise to ventral somatic mucles and a pair of unique cells that come to lie dorsomedially on top of the ventral nerve cord, the so-called DM cells. Cell ablation as well as cell transplantation experiments indicate that formation of the DM cells is induced by midline progenitors in the early embryo. These results are corroborated by genetic analyses. Mutant single minded embryos lack the CNS midline as well as the DM cells. Embryos mutant for any of the spitz group genes, which primarily express defects in the midline glial cell lineages, show reduced formation of the DM cells. Conversely, directed overexpression of secreted SPITZ by some or all CNS midline cells leads to the formation of additional DM cells. Furthermore we show that DM cell development does not depend on the absolute concentration of a local inductor but appears to require a graded source of an inducing signal. Thus, the Drosophila CNS midline cells play a central inductive role in patterning the mesoderm as well as the underlying ectoderm.

Animals↗
PubMed1997

Substrates and inhibitors of human T-cell leukemia virus type 1 (HTLV-1) proteinase.

Human T-cell leukemia virus type 1 (HTLV-1) proteinase, a 125 residue polypeptide, was chemically synthesized using the solid phase method. The crude product was purified, renaturated and proteolytic activity was tested using oligopeptide substrates derived from processing sites of various retroviral polyproteins. Cleavage of the oligopeptide substrates together with an initial study using a series of HIV-1 and MAV (myeloblastosis associated virus) proteinase inhibitors suggest that the substrate specificity of HTLV-1 proteinase is very close to that of BLV (bovine leukemia virus) proteinase and distinct from that of both HIV-1 and MAV proteinases.

Amino Acid Sequence↗
PubMed1997

[Elective premature delivery: clinical studies].

Cases of placental dysfunction complicated additionally by premature delivery were assessed. Abnormalities of pregnancy leading to chronic deficit in oxygenation were analyzed. Clinical utility of diagnostic procedures was evaluated. Neonatal condition in cases of elective premature birth versus spontaneous preterm delivery was compared.

Female↗
PubMed1996

Lability of N-alkylated peptides towards TFA cleavage.

Trifluoroacetic acid (TFA) is a common reagent in both solid-phase and solution peptide synthesis. It is used for the deprotection and/or cleavage of the synthesized peptide from the resin. The use of TFA under these standardized conditions is thought to be sufficiently mild, thereby preventing degradation of the desired product. However, peptides of the general structure R1-(N-alkyl X1)-X2-R2 are hydrolyzed by standard TFA solid-phase peptide synthesis (SPPS) cleavage/deprotection conditions providing fragments R1-(N-alkyl X1)-OH and H-X2-R2. The fragmentation is observed during a TFA cleavage both from the resin and in solution. The hydrolysis is proposed to proceed via an oxazolone-like intermediate in which equilibration of the chiral center of the N-alkylated residue occurs. This mechanism is supported by H/D exchange as observed MS and NMR in conjunction with HPLC.

Alkylation↗
PubMed1996

Peptide secondary structure mimetics: applications to vaccines and pharmaceuticals.

An important goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of multidomain proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. Mimetics of critical functional domains might possess beneficial properties in comparison to the intact proteinaceous species with regard to specificity and therapeutic potential, and are valuable probes for the study of molecular recognition events, and the development of novel vaccines and pharmaceuticals.

Amino Acid Sequence↗
PubMed1996

Progressive hemifacial atrophy: ten-year observation of a case.

The authors describe the case of a 14-year-old girl who experienced progressive hemifacial atrophy at the age of three-and-a-half years. The patient's early age at appearance of the condition resulted not only in atrophy of skin, subcutaneous tissue, and muscles, but also in very severe deformation of the right side of the face due to disorders in growth of cartilaginous and osseous tissue. Changes in her brain case and craniofacial skeleton included enophthalmos, underdevelopment of the eyelids, nose, hard plate, and dental process of the jaw including the premolar teeth, and a lack of the second molar. These changes caused an irregular line of bite. The differential diagnosis excluded hemifacial microsomy and sclerodermal hemifacial atrophy.

Adolescent↗