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1.
Sovrem Tekhnologii Med ; 14(5): 45-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37181833

RESUMO

The aim of the study is to develop a method for detection of pathological respiratory sound, caused by bronchial asthma, with the aid of machine learning techniques. Materials and Methods: To build and train neural networks, we used the records of respiratory sounds of bronchial asthma patients at different stages of the disease (n=951) aged from several months to 47 years old and healthy volunteers (n=167). The sounds were recorded with calm breathing at four points: at the oral cavity, above the trachea, on the chest (second intercostal space on the right side), and at a point on the back. Results: The method developed for computer-aided detection of respiratory sounds allows to diagnose sounds typical for bronchial asthma in 89.4% of cases with 89.3% sensitivity and 86.0% specificity regardless of sex and age of the patients, stage of the disease, and the point of sound recording.


Assuntos
Asma , Sons Respiratórios , Humanos , Sons Respiratórios/diagnóstico , Asma/diagnóstico , Computadores , Redes Neurais de Computação , Traqueia
2.
Disaster Mil Med ; 2: 16, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28265450

RESUMO

BACKGROUND: The International Preparedness & Response to Emergencies & Disasters (IPRED) conferences are conducted bi-annually in order to share insights and lessons learned from diverse crises. The aim of the article is to bring the IPRED conferences into better professional attention and to share the main insights that were presented in IPRED IV, which was held in January 2016. MAIN BODY: The major lessons learned included: Planning, regional/global collaboration and public-private cooperation should be implemented in developing novel technologies. International humanitarian action necessitates coordination between diverse actors concerning all potential threats. Leadership/coordination and decision-making capacities of emergency response leaders should be enhanced to ensure quality of care. Ethics in disaster management: Triage decisions must not discriminate against terrorists, even when attackers and victims are treated simultaneously. Resilience management: Establishing family and community networks increases resilience of individuals and society. Training programs & exercises must be evaluated considering cost-benefits. Human resources: Teams of experts should be transformed into expert teams. Communication: A common disaster-management language needs to be established. Social media is useful due to bi-directional communication. Civil-military cooperation should be established to facilitate a coordinated response including common terminologies and exercises. Animal sheltering: First responders and pet owners are jeopardized if animals are not included in emergency planning. Re-unification of animals with their owners should be included in response models. CONCLUSIONS: IPRED conferences provide a platform for sharing insights and lessons learned from diverse emergencies and disasters. The conferences offer a unique opportunity to share knowledge aimed at improving emergency preparedness, networking between various parties, and substantiates the knowledge and experience of all professionals who take part in the proceedings.

3.
Eksp Klin Gastroenterol ; (7): 139-41, 2016.
Artigo em Russo | MEDLINE | ID: mdl-30284743

RESUMO

Congenital anomalies of biliary tract development are frequent causes of lingering course of physiologic jaundice which need timely verification of diagnosis followed by surgical treatment. Clinical observation of biliary atresia in a 10-month-old girl permits to accent pediatricians' attention to peculiarities of clinical picture, diagnosis and techniques for treatment of this pathology.


Assuntos
Atresia Biliar , Vesícula Biliar , Atresia Biliar/diagnóstico , Atresia Biliar/fisiopatologia , Atresia Biliar/cirurgia , Feminino , Vesícula Biliar/anormalidades , Vesícula Biliar/fisiopatologia , Vesícula Biliar/cirurgia , Humanos , Lactente
4.
Comp Clin Path ; 24(6): 1325-1329, 2015 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-26478726

RESUMO

A 2-year-old domestic shorthair cat was presented with a history of hematuria, stranguria and intermittent urethral obstruction. Urine sediment showed hematuria, pyuria, and yellow-brown, amorphous and spherical crystals. Upon surgical correction of the obstructed urethra by perineal urethrostomy, many dark yellow to grey, irregular, gravel-like to millet grain-sized uroliths, consisting of 100% xanthine by crystallography were found. The urinary xanthine concentration was high. The cat subsequently developed bilateral nephroliths, recurrent urinary tract infection, and chronic kidney failure. Dietary management with a low-purine diet failed in part due to poor compliance, and the cat was euthanized at 6 years of age. Xanthinuria is rare inborn error of metabolism in cats and other species but should be considered as a differential diagnosis in cases of feline urolithiasis. No associated molecular genetic defect has been elucidated, and management of these cases is difficult. In the absence of calculi for analysis, measuring urinary xanthine concentration can help in diagnosing this metabolic defect.

5.
Artigo em Inglês | MEDLINE | ID: mdl-25966748

RESUMO

Transient Fanconi syndrome without azotemia was diagnosed in a dog and was associated with ingestion of Chinese chicken jerky treats. Fanconi syndrome is a proximal renal tubular defect and a diagnosis was made based upon severe glucosuria with normoglycemia, and severe generalized aminoaciduria. The clinical signs of polyuria and polydipsia as well as the massive urinary metabolic abnormalities resolved after jerky treat withdrawal. While frequently seen in North America and Australia, this is the first report of jerky treat induced Fanconi syndrome in continental Europe. Clinicians should be aware of this potential intoxication and be vigilant for a history of jerky treat consumption in a dog with glucosuria.


Assuntos
Doenças do Cão/etiologia , Síndrome de Fanconi/veterinária , Alimentos em Conserva/intoxicação , Produtos da Carne/intoxicação , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/terapia , Cães , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/etiologia , Síndrome de Fanconi/terapia , Feminino , Glicosúria/diagnóstico , Glicosúria/etiologia , Glicosúria/veterinária
6.
J Vet Intern Med ; 28(5): 1391-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25274437

RESUMO

BACKGROUND: Frequency and classification of anemia in terms of regeneration status and erythrocyte indices are not well described in cats. OBJECTIVE: To determine frequency and regenerative status of anemia in samples from adult cats, to assess the sensitivity and specificity of macrocytosis and hypochromasia for detecting regenerative anemia (RA), and to evaluate the association of anemia with increased serum creatinine concentration (SC). STUDY POPULATION: Laboratory records from 30,503 blood samples from cats (2003-2011). METHODS: Clinicopathologic data reviewed retrospectively. Anemia defined as hematocrit (Ht) ≤27%, red blood cell count (RBC) ≤5.5 × 10(6)/µL and hemoglobin (Hb) ≤9.0 g/dL. RA defined by manual absolute reticulocyte count >50 × 10(3)/µL. Macrocytosis was defined as mean corpuscular volume (MCV) >55 fL and hypochromasia as mean corpuscular hemoglobin concentration (MCHC) <31 g/dL. Cutoff for increased serum creatinine concentration was 1.6 mg/dL. RESULTS: Overall, 1,098 of 30,503 blood samples (3.6%) from cats fulfilled criteria for anemia, 633 of 1,098 (57.7%) classified as nonregenerative (NRA) and 465 of 1,098 (42.3%) as regenerative. RBC, Ht, and Hb were significantly lower in the RA compared to NRA group (P < .05). Sensitivity and specificity of the combined high MCV and low MCHC to detect samples with RA were 19.5 and 90.7%. SC was increased in 572 of the 1,098 anemic samples (52.1%) and in 11,121 of 29,405 of nonanemic samples (37.8%). CONCLUSIONS AND CLINICAL IMPORTANCE: Majority of anemic samples were classified as NRA. Anemia was more severe in cats with RA. Erythrocyte indices were not sensitive indicators of RA.


Assuntos
Anemia/veterinária , Doenças do Gato/sangue , Creatinina/sangue , Anemia/sangue , Anemia/classificação , Anemia/diagnóstico , Anemia Hipocrômica/sangue , Anemia Hipocrômica/diagnóstico , Anemia Hipocrômica/veterinária , Anemia Macrocítica/sangue , Anemia Macrocítica/diagnóstico , Anemia Macrocítica/veterinária , Animais , Contagem de Células Sanguíneas/veterinária , Doenças do Gato/diagnóstico , Gatos/sangue , Feminino , Hematócrito/veterinária , Masculino , Estudos Retrospectivos
7.
Science ; 321(5890): 821-3, 2008 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-18687960

RESUMO

Applying an electrical field to a polar polymer may induce a large change in the dipolar ordering, and if the associated entropy changes are large, they can be explored in cooling applications. With the use of the Maxwell relation between the pyroelectric coefficient and the electrocaloric effect (ECE), it was determined that a large ECE can be realized in the ferroelectric poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymer at temperatures above the ferroelectric-paraelectric transition (above 70 degrees C), where an isothermal entropy change of more than 55 joules per kilogram per kelvin degree and adiabatic temperature change of more than 12 degrees C were observed. We further showed that a similar level of ECE near room temperature can be achieved by working with the relaxor ferroelectric polymer of P(VDF-TrFE-chlorofluoroethylene).

8.
Neurol Res ; 21(8): 765-70, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10596386

RESUMO

Newborns are less sensitive than adults to hypoxic/ischemic injury. However, research into the mechanism of the newborn's relative resistance to reduced brain oxygen levels is relatively scarce, and the time-scale for the disappearance of resistance is not known. The multiprobe assembly (MPA) has enabled us to examine the resistance of puppies at various ages to hypoxia via continuous, simultaneous, on-line measurement of various ionic, metabolic and electrical parameters from the cerebral cortex. The parameters measured included electrocorticogram (ECoG), direct current (DC) steady state potential, extracellular potassium (Ke+) and calcium ion concentrations and intra-mitochondrial Nicotine amide adenine dinucleotide NADH redox levels. These parameters were measured under various degrees of hypoxia (fraction of inspiration oxygen was between 0-10%) in 6-h-old to 24-week-old puppies (n = 44). Sensitivity to hypoxia increased with age, being expressed in the leakage of potassium ions out of the cells (0.3 +/- 0.07 mM in the younger puppies and 3.0 +/- 1.3 mM in the older puppies) following an increase in intra-mitochondrial NADH redox levels. Potassium ion (Ke+) leakage was apparently due to depleted energy stores resulting from an impairment in the balance between oxygen supply and demand. Although the overall effect was similar, the kinetics of these changes were much faster in the older puppies. The time to initial increase of extracellular K+ was 2.5 +/- 0.1 min in the younger puppies and 0.9 +/- 0.1 min in the older puppies. The time to maximum increase of NADH was 3.2 +/- 0.2 min in the younger puppies and 1.4 +/- 0.1 min in the older puppies. Our results indicate that the older puppies utilize the existing oxygen faster than the younger puppies. It is concluded that the increased resistance of newborn puppies to hypoxia is due to intrinsic properties of the brain itself, like the ability of the membrane to maintain ionic homeostasis.


Assuntos
Animais Recém-Nascidos/metabolismo , Hipóxia Encefálica/metabolismo , Hipóxia/metabolismo , Fatores Etários , Animais , Cálcio/metabolismo , Córtex Cerebral/metabolismo , Cães , Eletroencefalografia , Metabolismo Energético/fisiologia , Feminino , Homeostase/fisiologia , Masculino , NAD/metabolismo , Oxirredução , Oxigênio/metabolismo , Oxigênio/farmacologia , Potássio/metabolismo
9.
Int J Psychoanal ; 80 ( Pt 1): 172, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10216824
10.
J Gastroenterol Hepatol ; 13(8): 821-4, 1998 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9736176

RESUMO

Infectious mononucleosis due to Epstein-Barr virus (EBV) is almost always a self-limited disease, most commonly seen in young adults. Hepatitis is a well-recognized complication of EBV infection that usually resolves spontaneously. Jaundice occasionally results from the unusual complication of autoimmune haemolytic anaemia rather than hepatitis. We report a 60-year-old man with severe cholestatic jaundice whose history, liver histology and laboratory findings suggested EBV infection. He also developed significant jaundice related to his hepatitis, but not to autoimmune haemolysis, a situation that led to diagnostic delay. Costly diagnostic laboratory tests and invasive procedures were performed to rule out a malignant extrahepatic biliary obstruction. Physicians need to be aware of this complication and EBV infection should be included in the differential diagnosis of cholestatic jaundice in the elderly.


Assuntos
Colestase/etiologia , Hepatite Viral Humana/diagnóstico , Herpesvirus Humano 4 , Mononucleose Infecciosa/complicações , Mononucleose Infecciosa/diagnóstico , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Diagnóstico Diferencial , Hepatite Viral Humana/complicações , Humanos , Masculino
11.
Brain Res ; 780(2): 230-6, 1998 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-9507147

RESUMO

Temporary interruption or reduction of cerebral blood flow during cerebrovascular surgery may rapidly result in ischemia or cerebral infarction. Thiopental has been shown to have cerebroprotective effects. However, the cerebroprotective dose of thiopental causes burst suppression of the EEG, thus this parameter cannot be used continuously for the detection of metabolic changes in the brain during thiopental anaesthesia. This study was performed in order to examine whether the multiparametric assembly (MPA), which measures energy metabolism CBF and mitochondrial (NADH) as well as extracellular ion concentrations (K+), can shed light on the mechanism of the cerebroprotective effects of thiopental. The MPA was placed on the brain of Mongolian gerbils and burst suppression of the ECoG was induced by thiopental. Cerebral ischemia was induced by occlusion of carotid arteries after burst suppression. Burst suppression of the ECoG was accompanied by a significant decrease in cerebral blood flow. In animals that received thiopental prior to ischemia, NADH increased to a lesser degree and extracellular potassium ion concentration increased to a lesser degree than in the control animals, indicating that thiopental affords protection of the brain under ischemic conditions due to improved energy metabolism. This study also demonstrates that the MPA can monitor changes occurring in the cerebral cortex even after the ECoG can no longer be used. Those findings have a significant value in the development of a new clinical monitoring device.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Córtex Cerebral/irrigação sanguínea , Moduladores GABAérgicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Tiopental/farmacologia , Animais , Arteriopatias Oclusivas/tratamento farmacológico , Isquemia Encefálica/metabolismo , Artérias Carótidas , Córtex Cerebral/metabolismo , Circulação Cerebrovascular , Eletroencefalografia , Espaço Extracelular/metabolismo , Gerbillinae , Mitocôndrias/metabolismo , Oxirredução , Potássio/metabolismo
12.
Brain Res ; 780(2): 323-8, 1998 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-9507177

RESUMO

Until recently carbon monoxide (CO) was known only for its noxious effects. Exposure to CO results in an autoregulatory increase in cerebral blood flow (CBF). Little information is available on brain energy metabolism under low CO concentrations and on the effect of CO on the stimulated brain. In this study cortical spreading depression (SD) was induced in order to cause transient brain depolarization and increased energy demand. The multisite assembly (MSA), which contains four bundles of optical fibers for monitoring the intramitochondrial NADH redox state and tissue reflectance as well as four DC electrodes enabling measurement from four consecutive points on the cerebral cortex, was used to measure energy metabolism and the propagation of SD waves during exposure to CO. CBF in the contralateral hemisphere was measured using the laser Doppler technique. Three experimental groups of animals were examined: SD was induced during exposure to 1000 ppm CO, immediately after exposure to CO and 90 min after cessation of exposure to CO. Three control groups were also examined, in which the animals underwent the same procedures but were not exposed to CO. In all animals exposure to CO was followed by a significant increase in CBF. The greatest effect was found when SD was induced immediately after cessation of exposure to CO. SD wave frequency decreased when induced immediately after exposure to CO, whereas it increased when SD was induced 90 min after exposure. The amplitude of the NADH oxidation waves and their integral were smaller during SD induced immediately after exposure to CO. The DC potential did not change, suggesting that CO did not affect the SD initiation mechanism but rather resulted in energy depletion during recovery from SD. This study demonstrates that even at a concentration of 1000 ppm CO interferes with the metabolic activity of the brain during repolarization of the SD-induced negativity.


Assuntos
Monóxido de Carbono/farmacologia , Córtex Cerebral/metabolismo , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Animais , Eletrofisiologia , Masculino , Mitocôndrias/metabolismo , NAD/metabolismo , Cloreto de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley
13.
Magn Reson Med ; 38(2): 285-95, 1997 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-9256110

RESUMO

A modified Prony method (MPM) was applied to analyze the main signals present in spatially resolved 31P NMR spectra of MCF7 breast tumors implanted in nude mice. First, the method was tested on synthetic data to establish its limits of reliability. Its performance with respect to peak identification and quantification of signal intensities was then exploited on data from three implanted tumors during hormonal manipulation with estrogen and the antiestrogenic drug tamoxifen. The phosphomonoester peak was resolved into phosphocholine (PC) and phosphoethanolamine (PE). Treatment with tamoxifen led to a significant reduction in the PE to PE+PC peak amplitude ratio in the tumors under consideration. MPM analysis also revealed the presence of two different inorganic phosphate pools: a larger acidic pool and a smaller alkaline pool during estrogen-induced growth and the reverse during tumor regression.


Assuntos
Antagonistas de Estrogênios/farmacologia , Estrogênios/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Mamárias Experimentais/metabolismo , Fosfatos/metabolismo , Tamoxifeno/farmacologia , Animais , Feminino , Camundongos , Camundongos Nus , Transplante de Neoplasias
15.
J Appl Physiol (1985) ; 81(3): 1078-83, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8889737

RESUMO

Carbon monoxide (CO) is known to be a toxic molecule due to the high affinity of hemoglobin for it. However, it has recently been shown that low doses of CO may play a physiological role. The aim of the present study was to examine processes occurring in the brain during exposure to 1,000 parts per million CO that result in an increase in cerebral blood flow (CBF) but are not accompanied by changes in oxidation metabolism. This study was carried out in awake rats with the multiprobe assembly developed in this laboratory for the simultaneous continuous measurement of CBF, intramitochondrial NADH redox levels, direct current potential, and extracellular concentrations of K+, Ca2+, and H+ as well as the electrocorticogram. Exposure to 1,000 parts per million CO in air resulted in an increased CBF without any concomitant changes in any of the other metabolic or ionic parameters measured. This indicates that tissue hypoxia was not the trigger for this vasodilation. Injection of N omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, before exposure to CO effectively blocked the increase in CBF that was observed when the animal was exposed to CO without prior injection of L-NNA. Furthermore, electrocorticographic depression was observed after the combined treatment of L-NNA and CO. In conclusion, exposure to relatively low doses of CO apparently does not have a deleterious effect on oxidative metabolism because the increase in CBF after this exposure is sufficient to prevent changes in oxidative metabolism, as indicated by the fact that NADH levels remained constant. This protective autoregulatory effect may be mediated by nitric oxide.


Assuntos
Encéfalo/efeitos dos fármacos , Monóxido de Carbono/farmacologia , Circulação Cerebrovascular/efeitos dos fármacos , Óxido Nítrico/farmacologia , Animais , Ratos
16.
J Am Psychoanal Assoc ; 44 Suppl: 429-47, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9170073

RESUMO

In working with mothers' responses to the total or partial loss of their child, it becomes evident that, at one level, they experience such a loss as an injury to the integrity of their body ego, which includes the child. Their capacity to invest the child as a bodily part of themselves as well as to release him and transfer bodily ownership to him in the course of personality growth necessitates flexible body boundaries. This characteristic of the female body ego is both gratifying and threatening to the mother as well as to others. It also has a profound impact on the growing boy's and girl's attempts to differentiate themselves from the mother bodily and to delineate their own sex-specific body ego. The nature and outcome of this difficult process has a significant effect on women's and men's attitudes to motherhood. These attitudes contain many defensive measures against the primitive anxieties of this early level, contributing perhaps also to the frequent neglect of motherhood in theories of female psychology.


Assuntos
Mães/psicologia , Poder Familiar/psicologia , Teoria Psicanalítica , Mulheres/psicologia , Adulto , Imagem Corporal , Criança , Ego , Relações Pai-Filho , Feminino , Identidade de Gênero , Humanos , Individuação , Masculino , Relações Mãe-Filho , Desenvolvimento Psicossexual , Caracteres Sexuais
17.
J Biol Chem ; 270(26): 15515-22, 1995 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-7797545

RESUMO

Pre-mRNA splicing occurs on spliceosomes, a family of ribonucleoprotein particles. Spliceosome assembly on exogenous adenovirus pre-mRNA was blocked at the A-complex (or pre-spliceosome) stage, either by destruction of the small nuclear ribonucleoproteins (snRNPs) that comprise the U4/U5/U6 tri-snRNP complex, or by interference in tri-snRNP assembly and interactions. The A-complex was isolated by size exclusion chromatography; homogeneity was shown by electrophoresis in nondenaturing polyacrylamide gels, gradient sedimentation, and electron microscopy. Northern hybridization showed U1 and U2 snRNAs to be present in the preparation, but not U4, U5, or U6. Antibodies specific for a component of the U1 snRNP or for a component that is common to all snRNPs (except U6) each precipitated an A-complex containing pre-mRNA, U1 and U2 snRNPs. Electron micrographs showed 230 x 270-A particles whose two components appear similar to individual U1 and U2 snRNPs. Electron micrographs of an A-complex-5'-biotinyl oligonucleotide-streptavidin-gold composite allowed identification of the U2 snRNP within the structure and the localization of the 5'-segment of U2 snRNA at a unique site in the A-complex. This region of U2 RNA is adjacent to the developing catalytic center of the spliceosome.


Assuntos
Ribonucleoproteínas Nucleares Pequenas/isolamento & purificação , Spliceossomos/ultraestrutura , Sequência de Bases , Células HeLa , Humanos , Microscopia Eletrônica , Dados de Sequência Molecular , Precursores de RNA/metabolismo , Splicing de RNA , Ribonuclease H/farmacologia , Ribonucleoproteína Nuclear Pequena U1/isolamento & purificação , Ribonucleoproteína Nuclear Pequena U2/isolamento & purificação , Ribonucleoproteínas Nucleares Pequenas/química , Ribonucleoproteínas Nucleares Pequenas/metabolismo
18.
Clin Chim Acta ; 228(1): 19-33, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7955426

RESUMO

Magnetic resonance imaging at high spatial resolution, dynamic-contrast enhanced imaging, and localized 31P magnetic resonance spectroscopy were applied to monitor in vivo growth and tamoxifen treatment of MCF7 human breast tumors implanted in athymic mice. Correlation of the imaging data with histological findings demonstrated significant differences between viable carcinoma, fibrous, and necrotic regions on T2 weighted images. At an early stage after tamoxifen treatment rapid necrosis preceded tumor regression suggesting tamoxifen inhibition of angiogenesis. The necrosis was followed by growth of reperative fibrous tissue at the boundary of the viable cancer cells and the necrotic regions. The dynamic of contrast enhancement after tamoxifen treatment revealed high permeability of microvessels at this boundary cord. In parallel to the induction of the repair process the tumor energy profile changed, showing a significant increase in the ratio of ATP to inorganic phosphate. Initial attempts to use MRI for evaluating the response of breast cancer patients to treatment are also described.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Imageamento por Ressonância Magnética , Trifosfato de Adenosina/análise , Animais , Neoplasias da Mama/metabolismo , Feminino , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Nus , Transplante de Neoplasias , Nucleotídeos/análise , Fosfatos/análise , Isótopos de Fósforo , Tamoxifeno/uso terapêutico
19.
Mol Cell Biol ; 14(4): 2731-9, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8139572

RESUMO

The intrinsic stimulatory potential or potency of a eukaryotic gene activator is controlled by the interaction between the activation domain and the transcriptional machinery. To further understand this interaction, we undertook a biochemical study to identify parameters that could be used to modulate activator potency. We considered how varying the number of activation domains, their flexibility, and the number of promoter sites affects potency in a yeast nuclear extract. The effects of GAL4 derivatives bearing either one, two, or four herpes simplex virus VP16 activation domains (amino acids 413 to 454) were measured on DNA templates containing one or two GAL4 sites in a Saccharomyces cerevisiae nuclear extract. We found that multimerized VP16 activation domains acted synergistically to increase the potency of the activators. The spacing between the activation domains was critical, such that the increased flexibility imparted by a protein linker contributed to increased activator potency. With highly potent activators, the levels of transcription stimulated on a single site were saturating, whereas the stimulatory effect of weaker activators increased with the number of sites. We discuss how these biochemical studies relate to the mechanism of gene activation and synergy in a yeast in vitro system.


Assuntos
Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Genes Fúngicos , Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Transcrição Gênica , Núcleo Celular/metabolismo , DNA Fúngico/metabolismo , Proteínas de Ligação a DNA , Proteínas Fúngicas/isolamento & purificação , Proteína Vmw65 do Vírus do Herpes Simples/isolamento & purificação , Modelos Biológicos , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Mapeamento por Restrição , Saccharomyces cerevisiae/metabolismo , Simplexvirus/metabolismo , Moldes Genéticos , Fatores de Transcrição/metabolismo , Ativação Transcricional
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