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P Simpson

Publications and source records attributed to P Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1997

u-shaped encodes a zinc finger protein that regulates the proneural genes achaete and scute during the formation of bristles in Drosophila.

The pattern of the large sensory bristles on the notum of Drosophila arises as a consequence of the expression of the achaete and scute genes. The gene u-shaped encodes a novel zinc finger that acts as a transregulator of achaete and scute in the dorsal region of the notum. Viable hypomorphic u-shaped mutants display additional dorsocentral and scutellar bristles that result from overexpression of achaete and scute. In contrast, overexpression of u-shaped causes a loss of achaete-scute expression and consequently a loss of dorsal bristles. The effects on the dorsocentral bristles appear to be mediated through the enhancer sequences that regulate achaete and scute at this site. The effects of u-shaped mutants are similar to those of a class of dominant alleles of the gene pannier with which they display allele-specific interactions, suggesting that the products of both genes cooperate in the regulation of achaete and scute. A study of the sites at which the dorsocentral bristles arise in mosaic u-shaped nota, suggests that the levels of the u-shaped protein are crucial for the precise positioning of the precursors of these bristles.

Amino Acid Sequence↗
PubMed1997

Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila.

The genes pannier (pnr) and u-shaped (ush) are required for the regulation of achaete-scute during establishment of the bristle pattern in Drosophila. pnr encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein. Genetic interactions between dominant pnr mutants bearing lesions situated in the amino-terminal zinc finger of the GATA domain and ush mutants have been described. We show here that both wild-type Pannier and the dominant mutant form activate transcription from the heterologous alpha globin promoter when transfected into chicken embryonic fibroblasts. Furthermore, Pnr and Ush are found to heterodimerize through the amino-terminal zinc finger of Pnr and when associated with Ush, the transcriptional activity of Pnr is lost. In contrast, the mutant pnr protein with lesions in this finger associates only poorly with Ush and activates transcription even when cotransfected with Ush. These interactions have been investigated in vivo by overexpression of the mutant and wild-type proteins. The results suggest an antagonistic effect of Ush on Pnr function and reveal a new mode of regulation of GATA factors during development.

Animals↗
PubMed1997

Notch signalling in development: on equivalence groups and asymmetric developmental potential.

Notch-mediated lateral signalling takes place between equivalent cells that then adopt alternative fates. An example is the epidermal-neural choice in the Drosophila neuro-ectoderm. Sometimes this choice is random. Sometimes it is biased to a preferred cell by an extrinsic signal. Sometimes the neural precursor is predetermined. A stochastic outcome is probably older in evolutionary terms.

Animals↗
PubMed1997

The LIN-12/Notch signaling pathway and its regulation.

Notch, LIN-12, and GLP-1 are receptors that mediate a broad range of cell interactions during Drosophila and nematode development. Signaling by these receptors relies on a conserved pathway with three core components: DSL ligand, LNG receptor, and a CSL effector that links the receptor to its transcriptional response. Although key functional regions have been identified in each class of proteins, the mechanism for signal transduction is not yet understood. Diverse regulatory mechanisms influence signaling by the LIN-12/Notch pathway. Inductive signaling relies on the synthesis of ligand and receptor in distinct but neighboring cells. By contrast, lateral signaling leads to the transformation of equivalent cells that express both ligand and receptor into nonequivalent cells that express either ligand or receptor. This transformation appears to rely on regulatory feedback loops within the LIN-12/Notch pathway. In addition, the pathway can be regulated by intrinsic factors that are asymmetrically segregated during cell division or by extrinsic cues via other signaling pathways. Specificity in the pathway does not appear to reside in the particular ligand or receptor used for a given cell-cell interaction. The existence of multiple ligands and receptors may have evolved from the stringent demands placed upon the regulation of genes encoding them.

Animals↗
PubMed1997

Transcriptional regulation of Notch and Delta: requirement for neuroblast segregation in Drosophila.

Segregation of a single neural precursor from each proneural cluster in Drosophila relies on Notch-mediated lateral signalling. Studies concerning the spacing of precursors for the microchaetes of the peripheral nervous system suggested the existence of a regulatory loop between Notch and its ligand Delta within each cell that is under transcriptional control. Activation of Notch leads to repression of the achaete-scute genes which themselves regulate transcription of Delta, perhaps directly. Here we have tested a requirement for transcriptional regulation of Notch and/or Delta during neuroblast segregation in embryos, by providing Notch and Delta ubiquitously at uniform levels. Neuroblast segregation occurs normally under conditions of uniform Notch expression. Under conditions of uniform Delta expression, a single neuroblast segregates from each proneural group in 80% of the cases, more than one in the remaining 20%. Thus transcriptional regulation of Delta is largely dispensable. We discuss the possibility that segregation of single precursors in the central nervous system may rely on a heterogeneous distribution of neural potential between different cells of the proneural group. Notch signalling would enable all cells to mutually repress each other and only a cell with an elevated neural potential could overcome this repression.

Animals↗
PubMed1997

Experience with gastrojejunal feeding tubes in children.

OBJECTIVE: Assessment of untoward symptomatic outcomes and major/minor complications occurring in children with percutaneous gastrojejunal tubes (GJT) in place. METHODS: A retrospective chart review of 28 patients with GJTs was performed. The diagnoses for these patients were: neurological diseases, 23; respiratory diseases, two; and gastrointestinal tract disorders, three. Twenty-three tubes were placed radiologically, four endoscopically, and one surgically. Patients' age range was between 1.5 and 180 months (mean 47.2 months), and weight at the time of tube insertion was between 2.28 and 42.7 kg. (mean 11.7 kg.). Duration of follow-up was from 1 to 49 months (mean 17.3 months). The patients were evaluated for the persistence or new development of the following symptoms: vomiting, hematemesis, abdominal pain, constipation, diarrhea, pain at the site of gastrostomy tube insertion, stridor with feeds, and dumping. Minor complications (including breakage, partial/total displacement, or dislodgement of GJT, tube occlusion, tube leakage, transient infection and/or granuloma at the gastrostomy site, and continued gastroesophageal reflux post-GJT conversion), as well as major complications (requiring surgical intervention) and mortality, were assessed. RESULTS: One or more symptoms either persisted or developed de novo in 20 children after tube insertion. Vomiting was the most common symptom, being present in 16 patients. One or more minor complication occurred in 21 patients; the most common was the accidental dislodgement of the jejunal feeding catheter. Major complications occurred in 11 patients (e.g., fundoplication in seven patients). Five patients died. Six patients had no complications; at the time of GJT placement, their mean age (93.3 months) was significantly older (p = 0.0269) and mean weight (21.3 kg.) significantly heavier (p = 0.0067) than those of children reporting major complications. CONCLUSIONS: We conclude that ongoing or new gastrointestinal symptoms and minor complications are common in children with GJT. However, GJT placement in larger children is associated with fewer complications than in smaller children.

Abdominal Pain↗
PubMed1997

Distribution of astigmatism among Sioux Indians in South Dakota.

BACKGROUND: Previous studies have reported a greater prevalence of high astigmatism and vision disorders among Native Americans than occurs in the general U.S. population. The majority of these studies, however, have focused on Native American schoolchildren. This study assessed the distribution of astigmatism in a general clinic population at the Rosebud Indian Reservation in South Dakota. METHODS: From examination of 174 patients, demographic information, visual acuities, refractive error, binocular vision status, and eye health were recorded. RESULTS: The data showed more high astigmatism than would be expected in a general U.S. population. Three or more diopters of astigmatism were found in 9.2% of the right eyes and 10.8% of the left eyes in the study population. High astigmatism was noted less frequently among those ages 40 years and older (3.3% right eyes, 6.3% left eyes). Most of the astigmatism was with-the-rule, but a shift toward against-the-rule and oblique astigmatism was found in older individuals. No significant gender differences were noted. CONCLUSIONS: The results suggest an ethnic difference in astigmatism and emphasize thee need for continued and expanded vision services for Native American populations.

Adolescent↗
PubMed1997

Juvenile rheumatoid arthritis in African Americans.

OBJECTIVE: To examine racial differences in disease expression in African American and Caucasian children with pauciarticular and polyarticular juvenile rheumatoid arthritis (JRA). METHODS: A retrospective chart review was conducted of 35 African American and 137 Caucasian children with pauciarticular and polyarticular JRA. RESULTS: African American children were significantly older than Caucasian children at the time of presentation. This was true both for the group as a whole and for each of the disease onset subtypes. African American children were less likely to have positive antinuclear antibody tests than Caucasian children. This finding paralleled a low incidence of uveitis in African American children. African American children were also more likely to have IgM rheumatoid factors (detected by latex agglutination) than Caucasian children. This was true even for African American children with pauciarticular JRA. CONCLUSION: There are significant phenotypic differences between African American and Caucasian children with JRA.

Adolescent↗
PubMed1996

A prepattern for sensory organs. Drosophila development.

The sensory bristles of Drosophila arise in stereotyped positions from small clusters of cells that express achaete-scute genes. A set of genes has now been identified that regulate achaete-scute expression and form a prepattern for sensory bristle development.

Animals↗
PubMed1996

A genetic analysis of pannier, a gene necessary for viability of dorsal tissues and bristle positioning in Drosophila.

A genetic and phenotypic analysis of the gene pannier is described. Animals mutant for strong alleles die as embryos in which the cells of the amnioserosa are prematurely lost. This leads to a dorsal cuticular hole. The dorsal-most cells of the imagos are also affected: viable mutants exhibit a cleft along the dorsal midline. pannier mRNA accumulates specifically in the dorsal-most regions of the embryo and the imaginal discs. Viable mutants and mutant combinations also affect the thoracic and head bristle patterns in a complex fashion. Only those bristles within the area of expression of pannier are affected. A large number of alleles have been studied and reveal that pannier may have opposing effects on the expression of achaete and scute leading to a loss or a gain of bristles.

Alleles↗
PubMed1996

Mapping of DFN2 to Xq22.

Non-syndromic X-linked deafness is a rare form of genetic deafness accounting for a small proportion of all hereditary hearing loss. It is both clinically and genetically heterogeneous and five loci have been described to date but only two of these have been mapped. DFN2 represents a locus for congenital profound sensorineural hearing loss that has yet to be mapped. We describe a four generation family with this phenotype in which female carriers have a mild/moderate hearing loss affecting the high frequencies. The mutant gene has been mapped to Xq22 using polymorphic microsatellite markers. A maximum two point lod score of 2.91 at theta = 0 was observed with a fully informative dinucleotide repeat at COL4A5, and flanking recombinations were observed at DXS990 and DXS1001.

Chromosome Mapping↗
PubMed1996

Dexamethasone for the prevention of postextubation airway obstruction: a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether dexamethasone prevents postextubation airway obstruction in young children. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Pediatric intensive care unit of a university teaching hospital. PATIENTS: Sixty-six children, < 5 yrs of age, intubated and mechanically ventilated for > 48 hrs. INTERVENTIONS: Patients were randomized to receive intravenous dexamethasone (0.5 mg/kg, maximum dose 10 mg) or saline, every 6 hrs for six doses, beginning 6 to 12 hrs before elective extubation. MEASUREMENTS AND MAIN RESULTS: Dependent variables included the presence of stridor, Croup Score, and pulsus paradoxus at 10 mins, 6, 12, and 24 hrs after extubation; need for aerosolized racemic epinephrine and reintubation. The dexamethasone and placebo groups were similar in age (median 3 months [range 1 to 57] vs. 4 months [range 1 to 59], p = .6), frequency of underlying airway anomalies (3/33 vs. 3/33, p = 1.0), and duration of mechanical ventilation (median 3.3 days [range 2.1 to 39] vs. 3.5 days [range 2.1 to 15], p = .7). The dexamethasone group had a lower frequency of stridor, Croup Score, and pulsus paradoxus measurement at 10 mins and at 6 and 12 hrs after extubation. Fewer dexamethasone-treated patients required epinephrine aerosol (4/31 vs. 22/32, p < .0001) and reintubation (0/31 vs. 7/32, p < .01). Three patients exited the study early-one patient in the dexamethasone group had occult gastrointestinal hemorrhage and one patient in each group had hypertension. CONCLUSION: Pretreatment with dexamethasone decreases the frequency of postextubation airway obstruction in children.

Airway Obstruction↗
PubMed1996

Genes of the Enhancer of split and achaete-scute complexes are required for a regulatory loop between Notch and Delta during lateral signalling in Drosophila.

Like the neuroblasts of the central nervous system, sensory organ precursors of the peripheral nervous system of the Drosophila thorax arise as single spaced cells. However, groups of cells initially have neural potential as visualized by the expression of the proneural genes achaete and scute. A class of genes, known as the 'neurogenic genes', function to restrict the proportion of cells that differentiate as sensory organ precursors. They mediate cell communication between the competent cells by means of an inhibitory signal, Delta, that is transduced through the Notch receptor and results in a cessation of achaete-scute activity. Here we show that mutation of either the bHLH-encoding genes of the Enhancer of split complex (E(spl)-C) or groucho, like Notch or Delta mutants, cause an overproduction of sensory organ precursors at the expense of epidermis. The mutant cells behave antonomously suggesting that the corresponding gene products are required for reception of the inhibitory signal. Epistasis experiments place both E(spl)-C bHLH-encoding genes and groucho downstream of Notch and upstream of achaete and scute, consistent with the idea that they are part of the Notch signalling cascade. Since all competent cells produce both the receptor and its ligand, it was postulated that Notch and Delta are linked within each cell by a feedback loop. We show, that, like mutant Notch cells, cells mutant for E(spl)-C bHLH-encoding genes or groucho inhibit neighbouring wild-type cells causing them to adopt the epidermal fate. This inhibition requires the genes of the achaete-scute complex (AS-C) which must therefore regulate the signal Delta. Thus there is a regulatory loop between Notch and Delta that is under the transcriptional control of the E(spl)-C and AS-C genes.

Animals↗
PubMed1996

[Role of the Notch receptors in intercellular communication].

The Notch gene was discovered in Drosophila at the beginning of the century and is currently the subject of intensive investigation, not only in invertebrates but also in vertebrates where remarkably well conserved homologues have been recently found. Notch encodes a new kind of cellular receptor whose functioning is still unclear and plays a role in a large number of cell interactions throughout development and in tissue renewal in the adult. Detailed study in invertebrates of some of these interactions has led to the identification of other genes required for transduction of the signal initiated by the receptor. Notch is always involved in processes where cells have the potential to choose between several different programmes of differentiation. Cells adopt a specific developmental pathway as a result of the inhibition of some programmes through Notch signalling. In this review we discuss the contribution of different experimental models to an understanding of the role of Notch in intercellular signalling.

Animals↗
PubMed1995

Inhibition of the pig to human xenograft reaction, using soluble Gal alpha 1-3Gal and Gal alpha 1-3Gal beta 1-4GlcNAc.

Natural anti-carbohydrate antibodies are central to hyperacute rejection in ABO-incompatible allotransplantation and in discordant xenotransplantation. ABO-incompatible rejection has been inhibited successfully using intravenous soluble carbohydrates as antibody inhibitors. The approach has been less successful previously in pig to primate xenotransplantation, where the necessary concentrations of a partial inhibitor (Gal alpha 1-6Glc) proved highly toxic. In this study, we have identified more effective inhibitors of the dominant human anti-pig antibodies that bind to the pentasaccharide Gal alpha 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-. The inhibitors are the terminal disaccharide (Gal alpha 1-3Gal) and terminal trisaccharide (Gal alpha 1-3Gal beta 1-4GlcNAc) of the target pentasaccharide. Twelve sera (3 from each ABO blood group) were tested in 3 different assays: lymphocytotoxic, lymphocyte flow cytometry, and solid-phase antigen ELISA. Fifty percent to 75% inhibition of human IgG and IgM was achieved using the disaccharide and trisaccharide inhibitors in the range of 10-50 mM. Disaccharide (70 mM) was used to inhibit hyperacute thrombosis in pig kidneys perfused for 40 min with heparinized human AB whole blood. The disaccharide completely inhibited red cell occlusion of glomerular but not of intertubular capillaries, although there was residual platelet thrombus in glomeruli. Disaccharide and trisaccharide can, therefore, be used in concentrations shown for other carbohydrate inhibitors to be nontoxic, for inhibition of hyperacute pig-to-human xenograft rejection. The inhibition is incomplete, however, and other antigen specificities and other rejection mechanisms are likely to be involved.

ABO Blood-Group System↗