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M Levine

Publications and source records attributed to M Levine.

At least 127 records · Page 7Linked to original sources
PubMed1998

TAFII mutations disrupt Dorsal activation in the Drosophila embryo.

In this study, we present evidence that the Dorsal activator interacts with limiting amounts of the TFIID complex in the Drosophila embryo. In vitro transcription reactions and protein binding assays implicate the TAFII110 and TAFII60 subunits of the TFIID complex in contributing to Dorsal-mediated activation. Mutations in TAFII110 and TAFII60 result in altered patterns of snail and twist transcription in embryos derived from dl/+ females. These results suggest that TAFIIs contribute to the activation of transcription in vivo and support the hypothesis that subunits of TFIID may serve as targets of enhancer binding proteins.

Animals↗
PubMed1998

GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo.

Insulator DNAs and promoter competition regulate enhancer-promoter interactions within complex genetic loci. A transgenic embryo assay was used to obtain evidence that the Drosophila eve promoter possesses an insulator activity that can be uncoupled from the core elements that mediate competition. The eve promoter contains an optimal TATA element and a GAGA sequence. The analysis of various chimeric promoters provides evidence that TATA is essential for promoter competition, whereas GAGA mediates enhancer blocking. The Trithorax-like (Trl) protein interacts with GAGA, and mutations in trl attenuate eve promoter insulator activity. We suggest that Trl-GAGA increases the stability of enhancer-promoter interactions by creating an open chromatin configuration at the core promoter.

Animals↗
PubMed1998

Evaluation of a patient file folder to improve the dissemination of written information materials for cancer patients.

BACKGROUND: Many cancer centers make available to patients written information material to supplement verbal information provided by clinicians. Randomized trials have demonstrated that providing such information can increase patient knowledge and satisfaction. However, little data are available regarding effective means of dissemination of such materials. The purpose of this study was to determine whether providing patients with a personal file folder after their first clinic appointment would improve the dissemination of written information materials and increase patient satisfaction. METHODS: A before/after study was performed. Consecutive patients with newly diagnosed cancer attending the Hamilton Regional Cancer Centre were selected randomly and interviewed by telephone within 1-2 weeks of the first clinic appointment regarding the number of information pamphlets received, patient satisfaction, and general preference for written information materials. The preintervention evaluation (T1) occurred over a 4-month period followed by the introduction of the personal file folder into the clinical practice. Six weeks after its introduction, the postintervention (T2) evaluation took place over the ensuing 4 months. RESULTS: A total of 300 patients completed the evaluation (150 each in T1 and T2). Responding patients in the two time periods were comparable with respect to background demographic variables. The mean number of information pamphlets received by patients increased with the introduction of the personal file folder from 2.4+/-2.0 standard deviations (SD) in T1 to 3.6+/-2.5 SD in T2 (P=0.0001). The percentage of patients planned for treatment who received treatment-related information increased from 36% (42 of 116 patients) in T1 to 65% (68 of 105 patients) in T2 (P=0.002). Mean patient satisfaction increased from 3.3+/-1.1 SD to 3.8+/-1.0 SD over the 2 time periods (P=0.0001). The majority of patients (87%) believed it was important to receive written information materials. CONCLUSIONS: The patient file folder increased the dissemination of written information materials and currently is being incorporated into routine practice.

Attitude↗
PubMed1998

Interaction of short-range repressors with Drosophila CtBP in the embryo.

Human CtBP attenuates transcriptional activation and tumorigenesis mediated by the adenovirus E1A protein. The E1A sequence motif that interacts with CtBP, Pro-X-Asp-Leu-Ser-X-Lys (P-DLS-K), is present in the repression domains of two unrelated short-range repressors in Drosophila, Knirps and Snail, and is essential for the interaction of these proteins with Drosophila CtBP (dCtBP). A P-element-induced mutation in dCtBP exhibits gene-dosage interactions with a null mutation in knirps, which is consistent with the occurrence of Knirps-dCtBP interactions in vivo. These observations suggest that CtBP and dCtBP are engaged in an evolutionarily conserved mechanism of transcriptional repression, which is used in both Drosophila and mammals.

Alcohol Oxidoreductases↗
PubMed1998

Lineage-specific regulation of the Ciona snail gene in the embryonic mesoderm and neuroectoderm.

The snail gene encodes a highly conserved, zinc-finger transcription factor that has been implicated in the specification of mesodermal and neuronal tissues in a variety of organisms. In the ascidian, Ciona intestinalis, snail (Ci-sna) is expressed at the 32-cell stage in derivatives of the B4.1 blastomere, including B6.2, B6.4, and B7.5, which give rise to the primary-lineage tail muscles of the tadpole. At later stages, Ci-sna is expressed in the lineages that will form the secondary tail muscle, the lateral ependymal cells of the spinal cord, and the dorsal cells of the cerebral vesicle. A minimal, 504-bp cis-regulatory sequence from the Ci-sna promoter region, the B4.1 enhancer, is shown to direct the expression of heterologous promoters in primary-lineage muscles. Furthermore, evidence is presented that cis-regulatory elements necessary for expression in both the secondary muscle and neuronal lineages are separate from the B4.1 enhancer. We discuss the possibility that the classical muscle determinant present in ascidian eggs may correspond to bHLH activators, which bind to specific E-box sequences contained in the B4.1 enhancer.

Animals↗
PubMed1998

Different core promoters possess distinct regulatory activities in the Drosophila embryo.

There are numerous examples of shared enhancers interacting with just a subset of target promoters. In some cases, specific enhancer-promoter interactions depend on promoter competition, whereby the activation of a preferred target promoter precludes expression of linked genes. Here, we employ a transgenic embryo assay to obtain evidence that promoter selection is influenced by the TATA element. Both the AE1 enhancer from the Drosophila Antennapedia gene complex (ANT-C) and the IAB5 enhancer from the Bithorax complex (BX-C) preferentially activate TATA-containing promoters when challenged with linked TATA-less promoters. In contrast, the rho neuroectoderm enhancer (NEE) does not discriminate between these two classes of promoters. Thus, certain upstream activators, such as Ftz, prefer TATA-containing promoters, whereas other activators, including Dorsal, work equally well on both classes of promoters. These results provide in vivo evidence that different core promoters possess distinct regulatory activities. We discuss the possibility that an invariant TFIID complex can adopt different conformations on the core promoter.

Animals↗
PubMed1998

Maintenance and recovery characteristics after sevoflurane or propofol during ambulatory surgery in children with epidural blockade.

PURPOSE: To compare the maintenance and recovery characteristics after sevoflurane with those after propofol in children with epidural blockade. METHODS: Fifty unpremedicated, children ASA I-II, 2-8 yr of age, scheduled for elective urological surgery as outpatients, were randomly allocated to receive either: 1) sevoflurane for induction and maintenance of anaesthesia or 2) propofol for induction (2-3 mg.kg-1 i.v.) and for maintenance (5-10 mg.kg-1.hr-1 i.v.). All children received N2O 70% in oxygen before induction and throughout the anaesthetic, rocuronium for neuromuscular blockade and a lumbar or caudal epidural block before incision. Heart rate (HR), systolic blood pressure (SBP), recovery times and all side effects during maintenance and recovery were recorded by a blinded observer. Adverse events during the first 24 hr were also recorded. RESULTS: Mean HR increased 5-10% after induction in both groups reaching a maximum by five minutes. Heart rate returned to baseline by skin incision in the sevoflurane group and by 10 min after induction in the propofol group. During maintenance, HR decreased by 10-20% below baseline values by 20 min in the propofol group only, where it remained for the remainder of the anaesthetic. Similarly, SBP increased by 10% after induction of anaesthesia in both groups, but returned to baseline by 10 min. Light anaesthesia occurred in four (16%) children, all in the propofol group. Emergence and recovery indices were similar in the two groups. DISCUSSION: Sevoflurane and propofol exhibit similar maintenance and recovery profiles when combined with epidural analgesia in children undergoing ambulatory surgery.

Ambulatory Surgical Procedures↗
PubMed1998

Shell differentiation and engrailed expression in the Ilyanassa embryo.

We have used in situ hybridization and immunocytochemistry to study the expression of the engrailed-related gene, Ily-en in embryos of the marine mud snail Ilyanassa obsoleta. We find that Ily-en is only expressed in shell gland cells. Only mRNAs localized in the shell gland hybridize to an antisense probe of the Ily-en homeobox. Similarly, only shell gland cells or shell-forming cells are stained by the monoclonal antibody 4D9, which was raised to the engrailed-class protein from Drosophila. Ilyanassa embryos made deficient in vegetal cytoplasm by removing the third polar lobe fail to differentiate an organized external shell. They do however make some randomly oriented internal shell fragments in which Ily-en is expressed. Because Ily-en is expressed in shell gland cells of both normal and lobeless embryos, we conclude that the determinant(s) required for Ily-en expression are not exclusively localized in the polar lobe.

Animals↗
PubMed1998

Ascidian embryogenesis and the origins of the chordate body plan.

For more than a century, ascidians have been a widely used system for classic embryological studies. Ascidians possess simple, well-defined cell-lineages, compact genomes, rapid development and world-wide distribution. Transgenic DNA can be introduced into developing embryos using simple electroporation methods. The ascidian larva represents the most simplified chordate body plan and provides a useful model for studying the molecular pathways underlying the morphogenesis and differentiation of the notochord and neural tube.

Animals↗
PubMed1998

Rush to judgment? Child protective services and allegations of sexual abuse.

Two hundred and ninety-three randomly selected cases from a child protection service agency in a large western New York county were examined to test the hypothesis that sexual abuse allegations are investigated and processed more intensively than cases alleging other types of maltreatment. Contrary to the hypothesis, allegations of sexual abuse were substantiated at a lower rate, not investigated more intensively, and not offered more services than were other cases.

Attitude of Health Personnel↗
PubMed1998

Supplemental social services improve outcomes in public addiction treatment.

AIMS: To evaluate the effectiveness and value of social services added to standard addiction rehabilitation. DESIGN: A controlled, quasi-experimental, field study with repeated measures. SETTING: Conducted in two groups of publicly supported outpatient addiction treatment programs. Control programs provided standard, twice-weekly, outpatient group counseling. "Enhanced" programs provided standard counseling but also case managers to coordinate and expedite use of pre-contracted medical screenings, housing assistance, parenting classes and employment services. MEASUREMENTS: The Addiction Severity Index was used to record the nature and severity of patient problems in seven areas at treatment admission and at 6-month follow-up. Services provided during treatment were measured with the Treatment Services Review. Measures were taken on consecutive samples of patients admitted to all programs--before enhancements (wave 1, N = 431)--and at 12 months (wave 2, N = 710); and 26 months following enhancements (wave 3, N = 187). FINDINGS: There were no significant differences in patient characteristics, treatment services or 6-month outcomes of the two sets of programs in wave 1. Wave 2 and especially wave 3 enhanced programs provided significantly more social and medical services than control programs. Patients treated in enhanced programs showed significantly less substance use, fewer physical and mental health problems and better social function at 6-months than Controls. CONCLUSIONS: Adding social services to public sector programs substantially improved the outcomes of addiction treatment. Changes in "real world" systems require time to implement; early evaluations may fail to capture the full impact of those changes.

Adult↗
PubMed1998

Cyclosporine monitoring in patients with renal transplants: two- or three-point methods that estimate area under the curve are superior to trough levels in predicting drug exposure.

The recent introduction of a cyclosporine microemulsion demonstrating less pharmacokinetic variability than the conventional formulation offers the potential for accurately and precisely predicting area under the curve (AUC) with a limited-sampling monitoring strategy. This was studied based on the pharmacokinetic profiles from 55 stable patients with renal transplants who were observed on two occasions at steady state on both formulations. Multiple linear regression analyses were performed on a training dataset from 27 patients, in which combinations of cyclosporine concentrations drawn from 0 to 4 hours postdose were regressed against the full AUC over the dosing interval. Predictor regression equations used concentration combinations ranging from one-point (concentrations at 0, 1, 2, 3, or 4 hours) through five-points (all five concentrations 0 to 4 hours). The predictive performance of these equations was then assessed in the training group with data from a subsequent profiling occasion and in the remaining 28 patients who constituted an independent test group. Prediction bias (mean prediction error) and prediction precision (absolute prediction error) were quantified and compared between formulations. Correlations between predicted and actual AUC were consistently stronger for the microemulsion, suggesting the possibility of more accurate and precise predictions of exposure than from the conventional formulation. For both formulations, the one-point predictors rendered the lowest prediction precision, and predictive performance improved considerably when multiple-point predictors were used. Significantly higher precision and lower variability were observed with the microemulsion for most predictors in the both training and test groups. For the microemulsion, two-point (C0 + C1 or C0 + C2) and three-point (C0 + C1 + C2) predictors yielded relatively unbiased and precise exposure predictions, inasmuch as mean absolute prediction error was less than 10% and 5%, respectively. Hence, a two- or three-point method may provide a clinically important improvement over the use of trough levels in monitoring cyclosporine therapy in patients with renal transplants.

Area Under Curve↗
PubMed1998

Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived macrophages: effects of cell activation.

We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human monocytes differentiate into macrophages in culture, and effects of the activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA). Western blot analysis demonstrated progressively increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5 expression during differentiation. Confocal microscopy revealed that each isoform displayed a unique subcellular distribution and cell-activation response. GLUT-1 was localized primarily to the cell surface but was also detected in the perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3 exhibited predominantly a distinct vesicle-like staining but was present only in monocytes. GLUT-5 was found primarily at the cell surface but was detectable intracellularly. Activation with fMLP induced similar GLUT-1 and GLUT-5 redistributions from intracellular compartments toward the cell surface. PMA elicited a similar translocation of GLUT-1, but GLUT-5 was redistributed from the plasma membrane to a distinct intracellular compartment that appeared connected to the cell surface. These results suggest specific subcellular targeting of each transporter isoform and differential regulation of their trafficking pathways in cultured macrophages.

Cell Differentiation↗
PubMed1998

Treatment of venous thromboembolism in cancer patients.

The occurrence of venous thromboembolism complicates the management of the patient with malignant disease because of the need for anticoagulant therapy. Cancer patients have an ongoing thrombotic stimulus due to the underlying cancer and its associated treatments, but are also considered to be at increased risk for anticoagulant-related bleeding. In recent years, the results of clinical trials have demonstrated the safety and efficacy of bodyweight-adjusted subcutaneous low-molecular-weight heparin administered at home for patients with acute deep vein thrombosis. This approach is particularly attractive in patients with cancer, in whom quality of life is an important consideration. There are no trials to date which specifically address the question of the duration of oral anticoagulant therapy in cancer patients. However, data can be extrapolated from trials evaluating the duration of oral anticoagulant therapy in other high-risk patients. Hence, cancer patients should continue oral anticoagulant therapy for as long the cancer remains active (usually at least 6 months). There remain a number of unanswered questions regarding the clinical management of thromboembolism in the cancer patient.

Administration, Oral↗