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PubMed1999

Translational regulation of oskar mRNA occurs independent of the cap and poly(A) tail in Drosophila ovarian extracts.

Translational regulation plays a prominent role in Drosophila body patterning. Progress in elucidating the underlying mechanisms has been limited by the lack of a homologous in vitro system that supports regulation. Here we show that extracts prepared from Drosophila tissues are competent for translation. Ovarian extracts, but not embryonic extracts, support the Bruno response element- and Bruno-dependent repression of oskar mRNA translation, which acts in vivo to prevent protein synthesis from transcripts not localized to the posterior pole of the oocyte. Consistent with suggestive evidence from in vivo experiments, regulation in vitro does not involve changes in poly(A) tail length. Moreover, inhibition studies strongly suggest that repression does not interfere with the process of 5' cap recognition. Translational regulation mediated through the Bruno response elements is thus likely to occur via a novel mechanism.

Animals↗
PubMed2002

Ypsilon Schachtel, a Drosophila Y-box protein, acts antagonistically to Orb in the oskar mRNA localization and translation pathway.

Subcellular localization of mRNAs within the Drosophila oocyte is an essential step in body patterning. Yps, a Drosophila Y-box protein, is a component of an ovarian ribonucleoprotein complex that also contains Exu, a protein that plays an essential role in mRNA localization. Y-box proteins are known translational regulators, suggesting that this complex might regulate translation as well as mRNA localization. Here we examine the role of the yps gene in these events. We show that yps interacts genetically with orb, a positive regulator of oskar mRNA localization and translation. The nature of the genetic interaction indicates that yps acts antagonistically to orb. We demonstrate that Orb protein is physically associated with both the Yps and Exu proteins, and that this interaction is mediated by RNA. We propose a model wherein Yps and Orb bind competitively to oskar mRNA with opposite effects on translation and RNA localization.

Animals↗
PubMed2002

EGFR signalling inhibits Capicua-dependent repression during specification of Drosophila wing veins.

Localised activation of the Ras/Raf pathway by Epidermal Growth Factor Receptor (EGFR) signalling specifies the formation of veins in the Drosophila wing. However, little is known about how the EGFR signal regulates transcriptional responses during the vein/intervein cell fate decision. We provide evidence that EGFR signalling induces expression of vein-specific genes by inhibiting the Capicua (Cic) HMG-box repressor, a known regulator of embryonic body patterning. Lack of Cic function causes ectopic expression of EGFR targets such as argos, ventral veinless and decapentaplegic and leads to formation of extra vein tissue. In vein cells, EGFR signalling downregulates Cic protein levels in the nucleus and relieves repression of vein-specific genes, whereas intervein cells maintain high levels of Cic throughout larval and pupal development, repressing the expression of vein-specific genes and allowing intervein differentiation. However, regulation of some EGFR targets such as rhomboid appears not to be under direct control of Cic, suggesting that EGFR signalling branches out in the nucleus and controls different targets via distinct mediator factors. Our results support the idea that localised inactivation of transcriptional repressors such as Cic is a rather general mechanism for regulation of target gene expression by the Ras/Raf pathway.

Animals↗
PubMed1992

Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.

Animals↗
PubMed1993

Fasting does not impair insulin-stimulated glucose uptake but alters intracellular glucose metabolism in conscious rats.

Effects of 24-h and 48-h fasting on maximal insulin-stimulated whole-body and muscle glucose uptake, glycogen synthesis, and glycolysis were studied in conscious rats by combining the glucose clamp technique with tracer methods. Fasting decreased body weight and basal plasma glucose, plasma insulin, hepatic glucose output, and glucose clearance (P < 0.05 for all). However, maximal insulin-stimulated whole-body glucose uptake, normalized to body weight, was almost identical in fed, 24-h fasted, and 48-h fasted rats (191 +/- 8, 185 +/- 14, and 182 +/- 5 mumol.kg-1.min-1, respectively; P > 0.7). Similarly, rates of insulin-stimulated glucose uptake by four different skeletal muscles, estimated by the 2-deoxyglucose injection technique, were not different among the three groups. In contrast to glucose uptake, insulin-stimulated whole-body glycolysis was decreased significantly after fasting (36% after 48 h fasting; P < 0.05), whereas insulin-stimulated whole-body glycogen synthesis was increased (44% after 48 h fasting; P < 0.05). In fed rats, glycolysis was the major pathway for glucose metabolism during hyperinsulinemia, accounting for 60 +/- 5% of glucose uptake. This fraction was decreased significantly by fasting (P < 0.01), so that after a 48-h fast, glycolysis accounted for only 40 +/- 3% of insulin-stimulated glucose uptake and glycogen synthesis became predominant pathway, accounting for 60 +/- 3% of whole-body glucose utilization. Whole-body patterns of glucose metabolism during hyperinsulinemia were paralleled by glucose metabolism in individual muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMedDate not supplied

Projecting future medical care costs using four scenarios of lifestyle risk rates.

PURPOSE: This study predicts medical care expenditures over 10 years for Union Pacific Railroad (UPRR) under alternative health risk factor scenarios for the UPRR workforce. DESIGN: This paper describes the development of an economic forecasting model to predict medical care expenditures assuming four different scenarios of population risk. The variables used to predict medical care expenditures are employee demographics and health risk profiles. SETTING: UPRR is a transportation company with more than 56,000 employees in 25 states west and south of the Mississippi River. SUBJECTS: Employees of UPRR. MEASURES: Intermediate outcomes included health risk measures related to exercise patterns, body weight, eating habits, smoking, alcohol consumption, total cholesterol, blood glucose, blood pressure, stress, and depression. Major outcome measures included projected total annual payments by UPRR for medical care services for the decade following 1998. RESULTS: The UPRR work force is projected to grow by 500 employees per year over the 10-year study period. The average age is expected to increase from 44 to 48 years. Without further health promotion intervention, 7 of the 11 risk factors assessed would likely worsen among UPRR's workforce. Medical care cost increases are projected to range from $22.2 million to $99.6 million in constant 1998 dollars over the next decade, depending on the effectiveness of risk factor modification programs. With an expected health promotion budget averaging $1.9 million annually over 10 years, health risks must decline at least 0.09% per year for the program to pay for itself. CONCLUSIONS: Estimating various risk and cost scenarios can facilitate program planning and produce an economic justification for worksite health programs.

Adult↗
PubMed1981

Behavioral assessment scale of oral functions in feeding.

When implementing therapeutic feeding programs for the multiply-handicapped developmentally disabled, it is imperative to establish a specific baseline of observable oral movement upon which management and change can be measured. The assessment reported provides an objective and graded method of documenting the major aspects of oral function in relation to feeding difficulties. It is designed to be used in conjunction with an assessment of overall muscle tone and body patterns and an evaluation of specific oral structures and deviations that might interfere with eating.

Adolescent↗
PubMed2000

A C. elegans patched gene, ptc-1, functions in germ-line cytokinesis.

Patched (Ptc), initially identified in Drosophila, defines a class of multipass membrane proteins that control cell fate and cell proliferation. Biochemical studies in vertebrates indicate that the membrane proteins Ptc and Smoothened (Smo) form a receptor complex that binds Hedgehog (Hh) morphogens. Smo transduces the Hh signal to downstream effectors. The Caenorhabditis elegans genome encodes two Ptc homologs and one related pseudogene but does not encode obvious Hh or Smo homologs. We have analyzed ptc-1 by RNAi and mutational deletion and find that it is an essential gene, although the absence of ptc-1 has no detectable effect on body patterning or proliferation. Therefore, the C. elegans ptc-1 gene is functional despite the lack of Hh and Smo homologs. We find that the activity and expression of ptc-1 is essentially confined to the germ line and its progenitors. ptc-1 null mutants are sterile with multinucleate germ cells arising from a probable cytokinesis defect. We have also identified a surprisingly large family of PTC-related proteins containing sterol-sensing domains, including homologs of Drosophila dispatched, in C. elegans and other phyla. These results suggest that the PTC superfamily has multiple functions in animal development.

Amino Acid Sequence↗
PubMed2000

New steps in the Wnt/beta-catenin signal transduction pathway.

Wnt regulates developmental and oncogenic processes through its downstream effector, beta-catenin, and a set of other intracellular regulators that are largely conserved among species. Wnt family genes encode secreted glycoproteins that act as ligands for membrane receptors belonging to the Frizzled family of proteins. Wnt-1 originally was found as a proto-oncogene that was upregulated in tumors caused by the mouse mammary tumor virus. The Drosophila homologue of Wnt-1, wingless, is a segment polarity gene that regulates body patterning of the fly embryo. In Xenopus, the Wnt pathway regulates formation of the ventral-dorsal axis. Although Wnt proteins are expressed widely in mammals, the function of the Wnt signaling pathway in normal adult mammalian tissues is not understood. Downstream components of the Wnt pathway, APC (adenomatous polyposis coli) and beta-catenin, clearly are involved in human cancer. There are also several reports that Wnt ligands are highly expressed in tumors. Wnt stabilizes cytoplasmic beta-catenin and activates beta-catenin/Lef-1 (lymphoid enhancer factor), Tcf (T-cell factor)-dependent gene transcription. This regulation of cytosolic beta-catenin is mediated by glycogen synthase kinase-3 (GSK-3) activity but in neither case is the mechanism known. The mechanism by which Wnt inhibits GSK-3 is unknown. Recent studies have shown that some of the intracellular signaling molecules that mediate the Wnt pathway are in complexes, including Dishevelled (Dsh or Dvl), GSK-3beta, and APC protein. However, little is known about how Wnt or other upstream stimuli regulate these complexes to stabilize beta-catenin. We took a variety of approaches to identify new components of the Wnt pathway. Using an expression-cloning technique, we isolated casein kinase I (CKI)epsilon as a positive regulator of beta-catenin in the Wnt pathway. Overexpression of CKIepsilon mimics Wnt by stabilizing beta-catenin, thereby increasing expression of beta-catenin-dependent genes. Inhibition of endogenous CKIepsilon attenuated gene transcription stimulated by Wnt or by Dsh. CKIepsilon forms a complex with Axin and the other downstream components of the Wnt pathway. CKIepsilon is a positive regulator of the Wnt pathway and a possible functional link between upstream signals and the intracellular Axin signaling complex that regulates beta-catenin. In separate experiments, we have identified a Dishevelled-associated kinase (DAK) that binds to Dsh and regulates its functions. Dsh is required for two different pathways, the Wnt pathway and planar polarity pathway in Drosophila. DAK dramatically enhances the function of Dsh in the Wnt pathway and inhibits its function in the planar polarity pathway. This chapter will discuss these newly identified components of the Wnt pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Teratogenic effects of sinusoidal extremely low frequency electromagnetic fields on morphology of 24 hr chick embryos.

To examine the potential teratogenicity of electromagnetic fields (EMF; sinusoidal and rectangular) on development of chick embryos (white leghorn), 221 freshly fertilized chicken eggs (55-65 g) were exposed during first 24 hr of postlaying incubation (38 degrees +/- 0.5 degree C) to 24 different EMFs, with 50Hz repetition rate and 8.007-10.143 mT flux density. Following exposure, the exposed fertilized chicken eggs (n = 8-10) and sham-exposed fertilized chicken eggs (n = 15) were incubated simultaneously for 8 more days and unexposed control fertilized chicken eggs (n = 20) for 9 days in absence of EMFs. The embryos were removed from egg shells and studied blind. All 24 EMF exposed-groups (inside the coil with exposure) showed an increase in the percentage of developmental anomalies compared to sham-exposed (inside the coil with no exposure) and control groups (outside the coil). Further, egg's weight was evaluated on day 9. This variable did not show significant difference between control and exposed-groups. The investigation also covered the measurement of body weight, length of crown to rump, length of tip of the beak to occipital bone, heart and liver weight. Statistical comparison between sham-exposed and control values did not show significant differences, but comparison between 8.007, 8.453 and 8.713 mT exposed-groups and control groups showed significant differences; in other exposed-groups, the changes were not significant. These results revealed that 50 Hz electromagnetic fields can induce irreversible developmental alterations in 24 hr chick embryos and confirm that its strength could be a determinant factor for the embryonic response to extremely low frequency electromagnetic fields (window effects).

Animals↗
PubMed2001

Siamois cooperates with TGFbeta signals to induce the complete function of the Spemann-Mangold organizer.

In Xenopus, the Spemann-Mangold organizer induces and patterns the body axis. Siamois, a Wnt-responsive transcriptional activator, functions to establish and maintain the Spemann-Mangold organizer by regulating organizer gene transcription. While expression of Siamois in marginal blastomeres induces an axis consisting of both head and trunk structures, we show that expression of Siamois in animal blastomeres induces an axis that lacks head structures. Consistent with the absence of head organizer activity in Siamois-expressing animal pole tissue, Siamois did not induce animal expression of Cerberus, Frzb1 and Xlim1, genes implicated in anterior development. A dominant negative form of Siamois inhibited endogenous expression of Cerberus, Frzb1 and Xlim1, indicating that Siamois is necessary for organizer-specific expression of these head organizer genes, but is not sufficient in animal tissue. Siamois induces Cerberus, Frzb1 and Xlim1 in vegetal blastomeres and vegetal induction by Siamois is dependent on endogenous TGFbeta signals. The results provide evidence that Siamois cooperates with TGFbeta signals to activate the expression of organizer genes and to generate an organizer with both head- and trunk-inducing activity.

Animals↗
PubMed1990

[Association of lichen planus and discoid lupus erythematosus. A clinical and histopathological study of 2 cases].

Two patients showing features of both lichen planus and lupus erythematosus are described: reticular whitish patches in the oral mucosa coexisting with chronic, partly atrophic LED-like skin lesions located on the face were present in both of them. The histological, histochemical and immunopathological findings allowed to diagnose a "LP-LE coexistence" more than a mixed LP-LE disease. The clinical, histological and immunological relationships between LP and LE are discussed and it is suggested that the pathogenesis of the coexistence of the two diseases could be related to a common pathophysiological pathway. It might be that LP and LE are due to a single aetiological agent (e.g. a virus) interacting with different genetic backgrounds to cause LE in some, LP in others and an intermediate disease in a small group of patients. The histopathological and immunopathological features that distinguish LP from LE are the concentration of lymphocytes in areas of keratinocyte damage, the different colloid bodies patterns and the direct IF findings. The Authors conclude that further studies should be performed on "LP-LE coexistence".

Adult↗
PubMed1990

[Urinary incontinence and prolapse. Medical treatment and functional treatment].

Urinary continence implies that the variations of the vesical pressure does not exceed the capacities of the cervico-urethral closure system. The aim of the various methods of treatment is to have a beneficial action on those two parameters: drug therapy will mainly reduce the intra-vesical pressure (parasympatholytics...) and also improve the urethral tone (alpha-adrenergics...), or have a mixed effect on both systems (tricyclic antidepressants, oestrogens...). The side effects are often numerous due to the impact on the vegetative or neuromuscular system. The re-education is complemented by: local and general kinesitherapy, sensorial retrocontrol, associated or not to electrotherapy. Motivation and active participation of the patient are essential. The indications covers all the various pathologies (perineal insufficiency, defects in the body pattern, prolapse, sphincteral insufficiency, transmission problems, vesical instability, urethral instability) and concerns patients of all age groups.

Biofeedback, Psychology↗
PubMed1988

Subtypes in major depression without melancholia.

Using the Diagnostic and Statistical Manual of Mental Disorders (DSM III, 1980) criteria to diagnose major depression without melancholia, 70 adult patients were selected for further detailed clinical and neuro-endocrinological evaluation. Two subtypes emerged; changes in sleeping patterns, body mass and thyrotrophin response to thyrotrophin-releasing hormone constituted the distinguishing features between the two categories (P = 0.012).

Adult↗
PubMed1986

General pharmacology of brotizolam in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo-diazepine with profound sedative and hypnogenic properties. The side effects of the drug on general behavior, motocoordination, feeding pattern, body temperature, uropoietic and gastrointestinal functions, cardiovascular system, and respiration, as well as interactions with some biogenic amines are reported and discussed. The findings correlate with those known for other diazepines. Accordingly, effects on motocoordination were prominent, but were limited to an ataxia, whereas even extremely high doses scarcely eliminated the postural reflexes. Sleeping animals could invariably be woken and were capable of locomotion; thus, no comatose condition developed. The cardiovascular functions were not appreciably altered by brotizolam in anesthetized cats, while in conscious dogs minor fluctuations of blood pressure and heart rate occurred. Respiration was clearly inhibited when brotizolam was given intravenously. The cardiovascular effects of acetylcholine, norepinephrine, epinephrine, isoprenaline, and histamine were only slightly modulated. The orexigenic and hypothermic effects equalled those of other diazepines. The functions of kidney, stomach, and intestines were not affected. The entirety of the observations procured in ten different species suggest that brotizolam is well tolerated when given orally.

Animals↗
PubMed1983

[Quantity of DNA, sex chromatin bodies and nucleoli in the nuclei of the muscle cells of normal and hypertrophied human atria].

Nuclei of myocytes of normal and hypertrophied human heart atrium were studied on squash preparations. Judging by the sex chromatin body pattern, it is the polyploidization that is responsible for the increased DNA contents in these nuclei. The cytophotometric DNA measurements demonstrated the up to 93% occurrence of polyploid nuclei even in myocytes of normal atrium. Myocytes of hypertrophied atrium contained nuclei of higher ploidy degrees. The total area of nucleoli per nucleus was shown to be proportional to a degree of ploidy.

Adult↗
PubMedDate not supplied

[Hemophilia: evaluation of the nutritional status and growth in childhood].

Haemophilia is a bleeding disorder characterized by decreased activity of the circulating antihemophilic factor, with different degrees of severity. The prognosis of the disease for an useful normal life is good, providing an adeguate follow-up. We think that the auxological determinants of growth and nutritional status must enter as points of a multicentre follow-up sheet of haemophilia in the pediatric age. We have tried such an approach in 13 patients; preliminary results have shown that all patients are growing well with some degrees of discrete malnutrition (arm circumference less than -1.6 SD). From costitutional point of view, haemophilic boys show a discrete "lean" body pattern (W/H2 less than or equal to O SD(with their trunk longer than legs. Data from other studies are wellcome for confirming our first impressions.

Anthropometry↗
PubMed1994

Cancer of the prostate: treatment and nursing implications.

PURPOSE/OBJECTIVES: To review the clinical manifestations, current treatment, and nursing management of prostate cancer. DATA SOURCES: Published articles, book chapters, American Cancer Society booklets. DATA SYNTHESIS: Prostate cancer is a slow-growing malignancy and usually is asymptomatic in its early stages. It causes acute urinary obstruction at more advanced stages, and patients may present with metastatic disease. Diagnosis is made by biopsy, and treatment options include periodic observation, surgery, radiotherapy hormonal manipulation, and chemotherapy with standard or investigational drugs or combination therapy. The major complications associated with surgery and radiation therapy are transient or permanent incontinence and impotence. CONCLUSIONS: Because no definitive method for identifying clinically important lesions exists, much controversy surrounds prostate cancer treatment. Issues significant to the diagnosis and treatment of all stages of prostate cancer are identified, and nursing care concerns focusing on treatment and disease-related problems are presented. IMPLICATIONS FOR NURSING PRACTICE: Nursing care focuses on providing patients with accurate information to make informed decisions regarding treatment for early stage disease, on promoting comfort, and on preventing and managing treatment and disease-related complications. Nursing diagnoses include knowledge deficit; altered sexual patterns, body image disturbance, altered urinary elimination, diarrhea, impaired skin integrity, and pain, fatigue, bleeding, and infection, all of which are related to surgery, pathologic fractures, spinal cord compression, and edema of the scrotum/lower extremities.

Humans↗