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P Simpson

Publications and source records attributed to P Simpson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Generation of medial and lateral dorsal body domains by the pannier gene of Drosophila.

The pannier (pnr) gene encodes a GATA transcription factor and acts in several developmental processes in Drosophila, including embryonic dorsal closure, specification of cardiac cells and bristle determination. We show that pnr is expressed in the mediodorsal parts of thoracic and abdominal segments of embryos, larvae and adult flies. Its activity confers cells with specific adhesion properties that make them immiscible with non-expressing cells. Thus there are two genetic domains in the dorsal region of each segment: a medial (MED) region where pnr is expressed and a lateral (LAT) region where it is not. The homeobox gene iroquois (iro) is expressed in the LAT region. These regions are not formed by separate polyclones of cells, but are defined topographically. We show that ectopic pnr in the wing induces MED thoracic development, indicating that pnr specifies the identity of the MED regions. Correspondingly, when pnr is removed from clones of cells in the MED domain, they sort out and apparently adopt the LAT fate. We propose that (1) the subdivision into MED and LAT regions is a general feature of the Drosophila body plan and (2) pnr is the principal gene responsible for this subdivision. We argue that pnr acts like a classical selector gene but differs in that its expression is not propagated through cell divisions.

Abdomen↗
PubMed2000

Expression of achaete-scute homologues in discrete proneural clusters on the developing notum of the medfly Ceratitis capitata, suggests a common origin for the stereotyped bristle patterns of higher Diptera.

The stereotyped positioning of sensory bristles in Drosophila has been shown to result from complex spatiotemporal regulation of the proneural achaete-scute genes, that relies on an array of cis-regulatory elements and spatially restricted transcriptional activators such as Pannier. Other species of derived schizophoran Diptera have equally stereotyped, but different, bristle patterns. Divergence of bristle patterns could arise from changes in the expression pattern of proneural genes, resulting from evolution of the cis-regulatory sequences and/or altered expression patterns of transcriptional regulators. Here we describe the isolation of achaete-scute homologues in Ceratitis capitata, a species of acalyptrate Schizophora whose bristle pattern differs slightly from that of Drosophila. At least three genes, scute, lethal of scute and asense have been conserved, thus demonstrating that gene duplication within the achaete-scute complex preceded the separation of the families Drosophilidae and Tephritidae, whose common ancestor goes back more than 100 million years. The expression patterns of these genes provide evidence for conservation of many cis-regulatory elements as well as a common origin for the stereotyped patterns seen on the scutum of many Schizophora. Some aspects of the transcriptional regulation have changed, however, and correlate in the notum with differences in the bristle pattern. The Ceratitis pannier gene was isolated and displays a conserved expression domain in the notum.

Amino Acid Sequence↗
PubMed1999

Lack of significant proximal esophageal acid reflux in infants presenting with respiratory symptoms.

The effects of proximal esophageal acid reflux on upper and lower respiratory tract symptoms in infants with gastroesophageal reflux (GER) remain controversial. We studied 116 infants with either respiratory or gastrointestinal symptoms to determine whether acid reflux in the proximal esophagus plays an etiologic role in the elicitation of respiratory symptoms in comparison to causing gastrointestinal (GI) symptoms only. Sixty-two infants (age range, 1-12 months) with respiratory symptoms suggestive of GER and 54 infants with gastrointestinal symptoms only (age range, 1-10 months) were evaluated with dual level esophageal pH monitoring. Mean duration of dual-level pH monitoring in infants with respiratory symptoms was 20.4 h, and in those with GI symptoms was 20.7 h. Seventeen of 54 infants with GI symptoms only and 16 of 63 infants with respiratory symptoms had abnormal distal esophageal acid reflux indices (i.e., pH <4.0 for >5% of the duration of study). In infants with abnormal distal pH monitoring, the median proximal acid reflux index in the GI group was 4.0% in comparison to 0.95% in the respiratory group (P < 0.01 by Wilcoxon rank sum W test). Values for other reflux parameters were also higher in the GI than in the respiratory group. We conclude that reflux-associated respiratory symptoms are more likely due to mechanisms other than the mere presence of refluxed acid in the proximal esophagus.

Case-Control Studies↗
PubMed1999

Two-dimensional echocardiography with a 15-MHz transducer is a promising alternative for in vivo measurement of left ventricular mass in mice.

Murine models of left ventricular (LV) hypertrophy recently have been developed. We tested the accuracy of 2-dimensional (2D) echocardiographic measurement of LV mass with high-frequency imaging in mice. Ten anesthetized mice (weight 20 to 31 g, aged 1 to 5 months) were examined with a 15-MHz transthoracic linear-array transducer. End-diastolic myocardial area (A)(epicardial - endocardial) from the parasternal short-axis view at the midpapillary level and LV length (L) from the parasternal long-axis view were measured to calculate LV mass with the area-length method (1.05 [5/6 x A x L]) and data were compared with LV-mass with the 2D guided M-mode method. Within 3 days of echocardiography, the hearts were removed and weighed after potassium-induced cardiac arrest. Two-dimensional echocardiographic measurement with a 15-MHz transducer was performed in all mice. LV chamber dimensions included end-diastolic septal (0.80 +/- 0.12 mm) and posterior wall thickness (0.76 +/- 0.13 mm), end-diastolic dimension (3.64 +/- 0.28 mm), and end-systolic dimension (2.34 +/- 0.32 mm). Echocardiographic LV mass with the area-length method, 2D guided M-mode method, and autopsy LV weight were 80.8 +/- 16.1 mg, 97.6 +/- 17.8 mg, and 78.8 +/- 13.2 mg, respectively. A strong correlation existed between LV weight (x ) and echocardiographic LV mass (y ) with the area-length method: y = 0.745x + 18.9, r =0.908, standard error of estimate (SEE) = 5.9 mg, P <.0005. This correlation was stronger than that of LV weight (x ) and echocardiographic LV mass (y ) with the 2D guided M-mode method: y = 0.577x + 22.6, r =0.779, SEE = 8.8 mg, P =.008. These data suggest that serial in vivo measurements of LV mass with the 2D area-length method may be more accurate than M-mode methods in experimental murine models of LV pathology.

Animals↗
PubMed1999

The use of hepatocyte extraction fraction to evaluate neonatal cholestasis.

PURPOSE: Hepatobiliary scintigraphy is used routinely to evaluate infants with neonatal cholestasis. Hepatobiliary scintigraphy determines biliary patency by detecting radioactivity in the bowel on imaging, in duodenal and gastric aspirates, or all of these. During hepatobiliary scintigraphy, the hepatocyte extraction fraction (HEF) is calculated by deconvolution analysis. Normal values of HEF are more than 90%. It is believed that HEF may predict hepatic dysfunction, because, during hepatobiliary scintigraphy, the radiopharmaceutical used in this test is extracted by the hepatocytes from the blood stream. Therefore, a low value of HEF is seen with more severe hepatocellular disease. The goal of this study was to determine whether HEF has any correlation with synthetic liver function, whether HEF can differentiate obstructive from nonobstructive lesions that cause neonatal cholestasis, and whether HEF can predict the outcome of the different causes of neonatal cholestasis. METHODS: A retrospective analysis of 68 hepatobiliary scintigraphy results was done in patients with neonatal cholestasis for a period covering 6 years. RESULTS: The HEF was available in 67 of these 68 patients, with a median value of 25% (range, 3.3% to 100%). The results of synthetic liver function tests (i.e., albumin and prothrombin time) were normal in all infants with neonatal cholestasis. No significant correlation was detected between HEF and the serum levels of total and direct bilirubin, albumin, alkaline phosphatase, and prothrombin time by exploratory data analysis (R = 0.08; small, P > 0.2). The HEF values in different causes of neonatal cholestasis were compared: extrahepatic biliary atresia, neonatal hepatitis, and a miscellaneous category consisting of alpha1-antitrypsin deficiency, ischemic hepatitis, paucity of bile ducts, and others. The outcomes of these diseases were assessed as resolution, continuing disease, transplantation, or death, but no predictive correlation was found with HEF. CONCLUSIONS: A single determination of HEF is of no value in assessing synthetic liver function (as assessed by albumin and prothrombin time), specific diagnoses, and outcomes in patients with neonatal cholestasis. Therefore, a low isolated value of HEF should not be considered suggestive of poor prognosis and outcome in these patients.

Biliary Tract↗
PubMed1999

Flumazenil in children after esophagogastroduodenoscopy.

OBJECTIVE: Our aim was to evaluate if the routine use of the benzodiazepine antagonist flumazenil would shorten postprocedure recovery times after esophagogastroduodenoscopy in pediatric patients receiving standard intravenous conscious sedation with the benzodiazepine diazepam in combination with meperidine. METHODS: Upper endoscopy was performed using intravenous conscious sedation with standardized doses of diazepam and meperidine on 29 children, age range 6-18 yr. Patients were randomized in a double-blind fashion to receive either intravenous normal saline (placebo) or 0.01 mg/kg (maximum, 1.0 mg) flumazenil within 5 min of procedure completion. Evaluation of the degree of sedation using a modified Observer' s Assessment of Alertness/Sedation Scale was performed presedation, immediately before reversal solution administration, and serially over 60 min after reversal solution injection. RESULTS: Fifteen patients received flumazenil and 14 received placebo; patient group composition did not vary significantly in age and weight. Fifty-four percent of flumazenil patients and 30% of control patients achieved full alertness within 10 min of reversal solution injection. However, this difference between groups was not significant (p > 0.45). Resedation or side effects directly attributable to flumazenil were not observed. CONCLUSIONS: A single postsedation dose of flumazenil is well-tolerated in children >6 yr old. However, its routine use after esophagogastroduodenoscopy is of questionable benefit in shortening recovery time in this age group.

Adolescent↗
PubMed1999

Urine drug screening.

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Gas Chromatography-Mass Spectrometry↗
PubMed1999

Different contributions of pannier and wingless to the patterning of the dorsal mesothorax of Drosophila.

In Drosophila, the GATA family transcription factor Pannier and the Wnt secreted protein Wingless are known to be important for the patterning of the notum, a part of the dorsal mesothorax of the fly. Thus, both proteins are necessary for the development of the dorsocentral mechanosensory bristles, although their roles in this process have not been clarified. Here, we show that Pannier directly activates the proneural genes achaete and scute by binding to the enhancer responsible for the expression of these genes in the dorsocentral proneural cluster. Moreover, the boundary of the expression domain of Pannier appears to delimit the proneural cluster laterally, while antagonism of Pannier function by the Zn-finger protein U-shaped sets its limit dorsally. So, Pannier and U-shaped provide positional information for the patterning of the dorsocentral cluster. In contrast and contrary to previous suggestions, Wingless does not play a similar role, since the levels and vectorial orientation of its concentration gradient in the dorsocentral area can be greatly modified without affecting the position of the dorsocentral cluster. Thus, Wingless has only a permissive role on dorsocentral achaete-scute expression. We also provide evidence indicating that Pannier and U-shaped are main effectors of the regulation of wingless expression in the presumptive notum.

Animals↗
PubMed1999

The development and evolution of bristle patterns in Diptera.

The spatial distribution of sensory bristles on the notum of different species of Diptera is compared. Species displaying ancestral features have a simple organization of randomly distributed, but uniformly spaced, bristles, whereas species thought to be more derived bear patterns in which the bristles are aligned into longitudinal rows. The number of rows of large bristles on the scutum was probably restricted to four early on in the evolution of cyclorraphous Brachyceran flies. Most species have stereotyped patterns based on modifications of these four rows. The possible constraints placed upon the patterning mechanisms due to growth and moulting within the Diptera are discussed, as well as within hemimetabolous insects. The holometabolic life cycle and the setting aside of groups of imaginal cells whose function is not required during the growth period, may have provided the freedom necessary for the evolution of elaborate bristle patterns. We briefly review the current state of knowledge concerning the complex genetic pathways regulating achaete-scute gene expression and bristle pattern in Drosophila melanogaster, and consider mechanisms for the genetic regulation of the bristle patterns of other species of Diptera.

Animals↗
PubMed1998

Polymorphism in the human anti-pig natural antibody repertoire: implications for antigen-specific immunoadsorption.

BACKGROUND: Anti-Galalpha1-3Gal antibodies cause hyperacute rejection (HAR) in pig-to-primate xenotransplantation. Long-term graft survival has not been achieved despite abrogation of HAR using transgenic pigs. IgG and IgM anti-Galalpha1-3Gal also play a role in the events following abrogation of HAR. Characterizing these antibodies and developing a system for their removal is therefore crucial to future success in xenotransplantation. METHODS AND RESULTS: We have developed a neoglycoprotein enzyme-linked immunosorbent assay to probe the precise antigenic requirements for the binding of anti-Galalpha1-3Gal and have analyzed 77 normal sera. Sixty-six percent of individuals have IgG that recognizes the Galalpha1-3Gal di-, tri-, and pentasaccharides (D, T, and P, respectively), termed DTP phenotype. The frequency of other phenotypes was - -P, 13%; -TP, 12%; D-P, 8%; and DT-, 1%. The IgG subclasses found were IgG2 (95%), IgG3 (34%), IgG1 (31%), and IgG4 (17%). IgM in 91% of individuals recognized all three antigens. Further antibody heterogeneity was demonstrated when immunoadsorbents derived from Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc (PENTA) were tested. Galalpha1-3Galbeta1-4Glc (TRI 6) or PENTA agarose were effective for IgG removal in all individuals. For IgM removal, two deoxy derivatives were completely successful in 73% of individuals. Combining the Galalpha1-3Gal (DI) and TRI 6 agarose produced an adsorbent that completely removed anti-Galalpha1-3Gal IgG and IgM in all individuals tested. CONCLUSIONS: Although the polymorphism in the anti-Galalpha1-3Gal repertoire, which we have demonstrated, represents a major obstacle to the development of an effective immunoadsorbent, the combination of DI and TRI 6 agarose appears sufficient for pig-to-human xenotransplantation.

Animals↗
PubMed1998

All three surface tryptophans in Type IIa cellulose binding domains play a pivotal role in binding both soluble and insoluble ligands.

The three surface tryptophans of the Type IIa cellulose binding domain of Pseudomonas fluorescens subsp. cellulosa xylanase A (CBD(XYLA)) were independently mutated to alanine, to create the mutants W13A, W49A and W66A. The three mutant proteins were purified, and their capacity to bind to a variety of ligands was determined. The mutant proteins have native-like structures but exhibited much weaker affinity for crystalline and amorphous cellulose and for cellohexaose than the wild type. These data indicate that all three tryptophans are important for binding to cellulose, and support a model in which the three tryptophans form an aromatic strip on the surface of the protein that binds to a single cellulose.

Bacterial Proteins↗
PubMed1998

Pseudomonas cellulose-binding domains mediate their effects by increasing enzyme substrate proximity.

To investigate the mode of action of cellulose-binding domains (CBDs), the Type II CBD from Pseudomonas fluorescens subsp. cellulosa xylanase A (XYLACBD) and cellulase E (CELECBD) were expressed as individual entities or fused to the catalytic domain of a Clostridium thermocellum endoglucanase (EGE). The two CBDs exhibited similar Ka values for bacterial microcrystalline cellulose (CELECBD, 1.62x10(6) M-1; XYLACBD, 1.83x10(6) M-1) and acid-swollen cellulose (CELECBD, 1.66x10(6) M-1; XYLACBD, 1.73x10(6) M-1). NMR spectra of XYLACBD titrated with cello-oligosaccharides showed that the environment of three tryptophan residues was affected when the CBD bound cellohexaose, cellopentaose or cellotetraose. The Ka values of the XYLACBD for C6, C5 and C4 cello-oligosaccharides were estimated to be 3.3x10(2), 1.4x10(2) and 4.0x10(1) M-1 respectively, suggesting that the CBD can accommodate at least six glucose molecules and has a much higher affinity for insoluble cellulose than soluble oligosaccharides. Fusion of either the CELECBD or XYLACBD to the catalytic domain of EGE potentiated the activity of the enzyme against insoluble forms of cellulose but not against carboxymethylcellulose. The increase in cellulase activity was not observed when the CBDs were incubated with the catalytic domain of either EGE or XYLA, with insoluble cellulose and a cellulose/hemicellulose complex respectively as the substrates. Pseudomonas CBDs did not induce the extension of isolated plant cell walls nor weaken cellulose paper strips in the same way as a class of plant cell wall proteins called expansins. The XYLACBD and CELECBD did not release small particles from the surface of cotton. The significance of these results in relation to the mode of action of Type II CBDs is discussed.

Bacterial Proteins↗
PubMed1998

Prevalence of microalbuminuria in children with sickle cell disease.

Renal involvement is common in homozygous sickle cell disease (HbSS), including glomerular hypertension and hypertrophy similar to that seen in rodent models of ablative nephrectomy and stage I diabetic nephropathy (DN). The proteinuria in the rodent models is attenuated by angiotensin converting enzyme inhibition (ACEI). Microalbuminuria (MA) is a sensitive marker for renal involvement in DN prior to the development of proteinuria, and is also attenuated with ACEI. Elevated urinary microalbumin/creatinine ratios (U Alb/Cr) >20 mg/g Cr are reported in 39%-43% of adults with HbSS, and studies are ongoing in this age group to assess the effect of attenuated proteinuria by ACEI on long-term renal function. The purpose of this study was to prospectively investigate the prevalence of MA in children with HbSS and determine factors which affect its expression. U Alb/Cr values were measured on spot urine samples in 102 children (aged 2-18 years, mean 9.47+/-4.62, M:F=53:49) by rate nephelometry. Children with prior known proteinuria, hypertension, or fever/pain episode in the last 15 days were excluded. MA was present in 26.5% of all children with HbSS. However, in children between the ages of 10 and 18 years, the prevalence was 46% (similar to the prevalence in adults). There was a strong correlation between patient age and prevalence of MA (P<0.0001) by both univariate and multivariate analysis. However, pain frequency, hospitalization, transfusion program, ferritin levels, and Cr clearance (C(Cr)) did not correlate with prevalence, although C(Cr) (as estimated by Schwartz formula) was elevated in all. We conclude that the prevalence of MA in the 2nd decade of life is similar to that in adults.

Adolescent↗
PubMed1998

Impaired exercise capacity late after cardiac transplantation: influence of chronotropic incompetence, hypertension, and calcium channel blockers.

BACKGROUND AND METHODS: Patients undergoing orthotopic cardiac transplantation manifest reduced exercise capacity during the first postoperative year, which is related primarily to chronotropic incompetence of the denervated heart. To determine whether exercise capacity improves during the long term after transplantation, we prospectively studied 45 patients from 1 month to 6 years after cardiac transplantation by use of maximal treadmill exercise testing for measurement of exercise duration, peak heart rate, and peak VO2. All had normal left ventricular ejection fractions. Patients were categorized according to length of time since transplant and compared to 14 untrained normal subjects. RESULTS: Peak exercise heart rate and exercise duration were progressively higher as time after transplantation increased. However, patients who had undergone transplantation more than 2 years earlier continued to manifest a significant reduction in peak exercise heart rate (157+/-3 beats/min vs 178+/-14 beats/min) and reduced exercise duration (8.6+/-0.5 minutes vs 13.2+/-2.0 minutes) compared with controls. In contrast, peak VO2 was similar at all times after transplant and remained markedly reduced in patients who underwent transplantation more than 2 years earlier as compared with controls (22.1+/-0.7 mL/kg/min vs 42.1+/-9.1 mL/kg/min). The potential effects of 14 clinical variables on exercise performance were evaluated by regression modeling. Patients with poorly controlled hypertension had a shorter median exercise duration (7.4 minutes vs 9.7 minutes) and a lower median peak VO2 (20.3 mL/kg/min vs 23.2 mL/kg/min) compared with patients with normal or well-controlled blood pressure. Patients treated with calcium channel blockers for hypertension had greater chronotropic incompetence during exercise (peak heart rate 139 beats/min vs 158 beats/min). There was no relation between exercise capacity and recipient age, donor age, recipient sex, donor ischemic time, pretransplant diagnosis, length of peritransplant hospitalization, percentage of ideal body weight, left ventricular ejection fraction, frequency or severity of allograft rejection, or long-term use of oral prednisone therapy. CONCLUSIONS: Exercise capacity, as measured by treadmill exercise time and peak heart rate, improves in the first 2 years after transplantation, but does not reach normal values in patients up to 6 years after transplant. Peak VO2 remains significantly reduced at all times after transplantation despite the presence of normal resting left ventricular systolic function.

Adult↗
PubMed1998

Use of Emergency Medical Service transport system in medical patients up to 36 months of age.

OBJECTIVES: To determine the frequency of inappropriate transport by Emergency Medical Service (EMS). DESIGN: A retrospective study. SUBJECTS: Patients up to 36 months of age with medical complaints transported by EMS to an urban pediatric emergency department (ED). INTERVENTIONS: None. MEASUREMENTS: Arbitrary criteria for appropriate use of EMS transport system were developed. The age, triage status, number of previous uses of EMS, health insurance status, time of calls, chief complaint, and clinical management of patients in the ED were determined. The frequency of inappropriate use of EMS was determined and also the percentage of patients up to 36 months of age who used EMS transport system on more than one occasion. RESULTS: Charts of 341 patients were reviewed of which 126 patients (37%) could have been transported by nonemergent vehicles according to our arbitrary criteria. In addition 97 (28%) of these patients had used the EMS transport system on at least one other occasion. CONCLUSIONS: EMS is utilized for inappropriate transportation in approximately 37% of our pediatric patients less than 36 months of age with medical complaints. In addition, 28% of these same patients utilized the EMS system on more than one occasion. It would appear that education of care providers in the appropriate use of EMS and use of alternate means of transportation would make the system more efficient and productive.

Ambulances↗
PubMed1998

Use of topical lidocaine in pediatric laceration repair: a review of topical anesthetics.

OBJECTIVE: To determine whether application of topical aqueous lidocaine to a laceration attenuates the pain from the subsequent lidocaine injection in children. DESIGN: Prospective, double-blind study. SETTING: A large, urban, tertiary care children's hospital emergency department. PATIENTS: A convenience sample of 100 children, five to 16 years of age, presenting with simple lacerations over a six-month period. INTERVENTIONS: An unlabelled 3-ml solution of either 1% lidocaine or placebo (saline) was used to soak a Telfa pad (Kendall, Mansfield, MA) and then placed onto the laceration for 10 minutes. The wound was then injected with 1% lidocaine, irrigated, and sutured per standard emergency department protocol. Independent pain response was elicited from the patient and parent four times: before any intervention, after the soak, after the injection, and at the end of the procedure. Blood pressure and heart rates were recorded at the same intervals. RESULTS: Four patients were excluded. Of the 96 remaining patients, 46 received the placebo and 50 received lidocaine. Age, sex, race, and laceration length and location were similar between groups. Physiologic parameters did not differ between groups. For all four pain ratings, the independent variables of age, sex, race, and laceration length or location did not differ between groups. Topical lidocaine was ineffective in relieving pain from the injection. When groups were combined, a significant negative correlation was noted for age versus injection pain (P = .035), with older children reporting less pain from injection than younger children. CONCLUSION: For children, soaking a simple laceration with 1% lidocaine does not decrease pain from the subsequent lidocaine injection.

Adolescent↗
PubMed1997

Requirement for dynamin during Notch signaling in Drosophila neurogenesis.

Singling out of a unique neural precursor from a group of equivalent cells, during Drosophila neurogenesis, involves Notch-mediated lateral signaling. During this process, activation of the Notch signaling pathway leads to repression of neural development. Disruption of this signaling pathway results in the development of an excess of neural cells. The loss of activity of dynamin, which is encoded by the gene shibire and is required for endocytosis, results in a similar phenotype. Here we have investigated the requirement of shibire function for Notch signaling during the segregation of sensory bristles on the notum of the fly. Overexpression of different constitutively active forms of Notch in shibire mutant flies indicates that shibire function is not necessary for transduction of the signal downstream of Notch, even when the receptor is integrated in the plasma membrane. However, when wild-type Notch is activated by its ligand Delta, dynamin is required in both signaling and receiving cells for normal singling out of precursors. This suggests an active role of the signaling cell for ligand-mediated receptor endocytosis in the case of transmembrane ligands. We discuss the possible implications of these results for normal functioning of Notch-mediated lateral signaling.

Animals↗