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1.
Rev Med Liege ; 67(10): 520-6, 2012 Oct.
Artigo em Francês | MEDLINE | ID: mdl-23167161

RESUMO

Oxybutynin is being increasingly being prescribed in the treatment of hyperhidrosis but currently, there is no precise dosage for this treatment. Nine patients were treated for primary hyperhidrosis resistant to conventional therapies with oxybutynin between January to May 2010. The treatment was progressively increased at 7.5 mg per day. Oxybutynin efficacy was evaluated by iodine starch test and biometrological measurements at 2 and 4 weeks of treatment. Hyperhidrosis Disease Severity Scale (HDSS) and Dermatology Life Quality Index (DLQI) were obtained for each patient. The means of HDSS and DLQI were respectively 3.2 +/- 0.7 and 17.0 +/- 5.1 before treatment and were 1.8 +/- 0.4 and 4.6 +/- 4.4 at 4 weeks of treatment. Oxybutynin at 7.5 mg per day significantly decreased intensity and area of sweat for palms but not for soles. Trans Epidermal Water Loss, conductance, pH and Skin temperature were modified with treatment. Oxybutynin at 7.5 mg per day has improved patient's quality of life. Efficiency of oxybutynin in primary palmar hyperhidrosis was proved by biometrological measurements and iodine starch test.


Assuntos
Hiperidrose/tratamento farmacológico , Ácidos Mandélicos/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Administração Oral , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Adulto Jovem
2.
Arch Mal Coeur Vaiss ; 98(11): 1149-54, 2005 Nov.
Artigo em Francês | MEDLINE | ID: mdl-16379113

RESUMO

The in-hospital management and short- and long-term outcomes was assessed in 2 registries of consecutive patients admitted for acute myocardial infarction, 5 years apart, in France. The 2000 cohort was younger and with a less frequent history of cardiac diseases, but was more often diabetic and with anterior infarcts. Time to admission was actually longer in 2000 than in 1995 (median 5.25 hours vs 4.00 hours). Overall, reperfusion therapy was used in 43% of the patients in both registries. However, the use of reperfusion therapy increased from 1995 to 2000 in patients admitted within 6 hours of symptom onset (64 vs 58%), with an increasing use of primary angioplasty (from 12 to 30%). Five-day mortality significantly improved from 7.7 to 6.1% (p < 0.03) and one-year survival was also less in the most recent period (85 vs 81%, p < 0.01). Multivariate analyses showed that the period of inclusion (2000 vs 1995) was an independent predictor of both short- and long-term mortality in patients admitted within 6 hours of symptom onset. Thus, in the real world setting, a continued decline in one-year mortality was observed in patients admitted to intensive care units for recent acute myocardial infarction, especially for patients admitted early. This goes along with a shift in reperfusion therapy towards a broader use of primary angioplasty, and with an increased use of the early prescription of recognised secondary prevention medications.


Assuntos
Hospitalização , Infarto do Miocárdio/terapia , Fatores Etários , Idoso , Angioplastia Coronária com Balão/estatística & dados numéricos , Complicações do Diabetes , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Reperfusão Miocárdica/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Sistema de Registros , Acidente Vascular Cerebral/complicações , Análise de Sobrevida , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico
3.
Heart ; 90(12): 1404-10, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15547013

RESUMO

OBJECTIVE: To assess actual practices and in-hospital outcome of patients with acute myocardial infarction on a nationwide scale. METHODS: Of 443 intensive care units in France, 369 (83%) prospectively collected data on all cases of infarction (within < 48 hours of symptom onset) in November 2000. RESULTS: 2320 patients (median age 68 years, 73% men) were included, of whom 83% had ST segment elevation infarction (STEMI). Patients without STEMI were older and had a more frequent history of cardiovascular disease. Median time to admission was 5.0 hours for patients with and 6.5 hours for those without STEMI. Reperfusion therapy was used for 53% of patients with STEMI (thrombolysis 28%, primary angioplasty 25%). In-hospital mortality was 8.7% (5.5% of patients without and 9.3% of those with STEMI). Multivariate analysis found that age, Killip class, lower blood pressure, higher heart rate on admission, anterior location of infarct, STEMI, diabetes mellitus, previous stroke, and no current smoking independently predicted in-hospital mortality. At hospital discharge, 95% received antiplatelet agents, 75% received beta blockers, and over 60% received statins. Angiotensin converting enzyme inhibitors were prescribed for 40% of the patients without and 52% of those with ST elevation. CONCLUSIONS: This nationwide registry, including all types of centres irrespective of their size and experience, shows continued improvement in patient care and outcomes. Time from symptom onset to admission, however, has not improved in recent years and reperfusion therapy is used for just over 50% of patients with STEMI, with an increasing use of primary angioplasty.


Assuntos
Cuidados Críticos/métodos , Hospitalização , Infarto do Miocárdio/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Angioplastia Coronária com Balão/métodos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/terapia , Reperfusão Miocárdica/métodos , Estudos Prospectivos , Sistema de Registros , Terapia Trombolítica/métodos , Resultado do Tratamento
4.
Ann Cardiol Angeiol (Paris) ; 53(1): 12-7, 2004 Jan.
Artigo em Francês | MEDLINE | ID: mdl-15038522

RESUMO

We assessed the in-hospital management and short- and long-term outcomes of two series of patients admitted for acute myocardial infarction, 5 years apart, in France. The most recent cohort was younger and with a less frequent history of cardiac diseases, but was more often diabetic and with anterior infarcts. Five-day mortality significantly improved from 7.7% to 6.1% (P < 0.03) and 1-year survival was also less in the most recent period (15% versus 19%, P < 0.01). Multivariate analyses showed that the period of inclusion (2000 versus 1995) was an independent predictor of both short- and long-term mortality. In analyses restricted to the patients who were alive by day 5, initial treatment with statins was associated with a 38% decrease in the risk of death at 1 year. Likewise, in patients with left ventricular ejection fraction < or = 35%, the early prescription of ACE inhibitors was associated with a 41% reduction in the risk of 1-year mortality. Thus, in the real world setting, a continued decline in 1-year mortality is observed in patients admitted to intensive care units for recent acute myocardial infarction. This goes along with a shift in reperfusion therapy towards a broader use of coronary angioplasty and with an increased use of the early prescription of recognised secondary prevention medications.


Assuntos
Mortalidade/tendências , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Idoso , Angioplastia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Coortes , Feminino , França/epidemiologia , Hospitais/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Fatores de Risco , Volume Sistólico , Resultado do Tratamento
5.
Rev Neurol (Paris) ; 159(8-9): 767-74, 2003 Sep.
Artigo em Francês | MEDLINE | ID: mdl-13679719

RESUMO

Handipark, a new score for measuring the impact of Parkinson's disease on daily life activities is presented. The global score ranging from 1 to 10 (without half points) is easy to determine. For a given patient, the score takes into account 5 items describing the global impact of the disease;Inter- and intra-observer reproducibility were determined. The reliability of the score was tested during two sessions separated by a 3-week interval. Five qualified neurologists scored 30 Parkinson's patients presented randomly for scoring using a semi-structured video-recorded interview. Intra-observer reproducibility was good (concordance coefficient; k=0.74, Spearman's correlation coefficient; r=0.88). Inter-observer reproducibility was also good: r=0.96 (first session), r=0.87 (second session); the agreement coefficient between the 5 observers was k=0.85 (first session), k=0.82 (second session). Distribution curves of the Hanipark score was described in 150 Parkinson's disease patients to study the correlation with items of other scales specific for Parkinson's disease (UPDRS, Hoehn & Yahr). A number significant correlations were found. Handipark is a reliable tool easy to use in clinical practice by a large panel of physicians caring for Parkinson's disease patients to assess the impact of Parkinson's disease. Further studies are needed to assess its usefulness for the follow-up of patients and assess the therapeutic impact.


Assuntos
Atividades Cotidianas/psicologia , Testes Neuropsicológicos , Doença de Parkinson/psicologia , Idoso , Comportamento Alimentar , Feminino , Humanos , Atividades de Lazer , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Ocupações , Estudos Prospectivos , Reprodutibilidade dos Testes , Viagem
6.
Ann Dermatol Venereol ; 127(3): 273-8, 2000 Mar.
Artigo em Francês | MEDLINE | ID: mdl-10804300

RESUMO

BACKGROUND: Acne is the most common symptom prompting patients to consult a dermatologist. No previous study has been conducted in France to determine the prevalence of acne and describe the main epidemiological features. SUBJECTS AND METHODS: A cross sectional study was conducted in November 1996 and included 913 school children aged 11 to 18 years. This sample was statistically representative of the entire secondary school population in France during the 1996-1997 school year. The subjects were stratified by 5 criteria: age, sex, rural or urban residence, sun exposure, type of school. RESULTS: Taking the clinical diagnosis made by the dermatologist investigator as the main criteria, the overall prevalence of acne was 72 p. 100. It was 76.1 p. 100 using the new ECLA grading system previously described. The prevalence of acne was sex and age dependent: highest scores were found for girls aged 14-16 years and for boys aged 16-17 years. Genetic factors were very important for the outcome of acne. Finally, 41 p. 100 of the acneic subjects were following a treatment, prescribed by a dermatologist in two-third of the cases. DISCUSSION: These results are in agreement with those previously published in the literature although some differences were disclosed. It would appear important to distinguish between minimal acne with a few retentional pimples occuring during adolescence and severe acne (more than 20 pimples on the face) requiring early medical care to avoid scarring.


Assuntos
Acne Vulgar/epidemiologia , Estudantes/estatística & dados numéricos , Acne Vulgar/etiologia , Adolescente , Criança , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Incidência , Masculino , Fatores de Risco
7.
J Gynecol Obstet Biol Reprod (Paris) ; 28(4): 319-29, 1999 Jul.
Artigo em Francês | MEDLINE | ID: mdl-10480062

RESUMO

INTRODUCTION: A strong rise in the use of induced labor has been observed in France. The aim of this work was to analyze the different methods used for achieving induction of labor and their implications. METHODS: One out of four French obstetricians were randomly selected to answer a questionnaire on their practice for achieving induction of labor. Four hundred of the 997 obstetricians answered the questionnaire. Univariate and multivariate analysis was applied. RESULTS: A high rate of induced labor was correlated with some areas of the country and with private practice. Certain methods were used in spite of opposing advice by experts in the field: elective induction of labor with unfavorable cervix, use of prostaglandins in elective induction of labor, induction of labor in cases of scarred uterus or breech presentation, use of misoprostol. Some methods were still used in spite of their poor efficacy: intravenous oxytocin used with unfavorable cervix, use of intravensou PGE2. CONCLUSION: This study would show that theory and practice are often distinctly different. Induction of labor is currently used on a far wider scale than ever before. We obviously need studies for careful assessment of the circumstances in which induction of labor is used in order to improve methods and indications of such a clinical practice.


Assuntos
Trabalho de Parto Induzido/métodos , Trabalho de Parto Induzido/estatística & dados numéricos , Obstetrícia/métodos , Obstetrícia/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Análise de Variância , Feminino , França , Pesquisas sobre Atenção à Saúde , Humanos , Trabalho de Parto Induzido/tendências , Modelos Logísticos , Obstetrícia/tendências , Ocitócicos , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/tendências , Gravidez , Prática Privada/estatística & dados numéricos , Características de Residência/estatística & dados numéricos , Inquéritos e Questionários
8.
Arterioscler Thromb Vasc Biol ; 16(10): 1243-9, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8857920

RESUMO

Paraxonase, an enzyme associated with the high density lipoprotein (HDL) particle, hydrolyzes paraoxon, the active metabolite of the insecticide parathion. Several studies have shown that paraxonase levels in humans have a distribution characteristic of two alleles, one with low activity and the other with high activity. Paraoxonase also has arylesterase activity, which does not exhibit activity polymorphism and can therefore serve as an estimate of enzyme protein. Although the ability of paraoxon to irreversibly inhibit lipoprotein lipase (LPL) has been exploited experimentally for many years, the role of plasma paraoxonase in lipoprotein metabolism is unknown. Seventy-two normal individuals were examined for paraoxonase genotypes, plasma paraoxonase and arylesterase activities, postheparin LPL and hepatic lipase (HL) activities, and lipoprotein levels to determine whether (1) paraoxonase activity or genotype determines lipoprotein levels via an effect on LPL or HL activity or (2) variation in LPL and HL activities determines HDL levels and indirectly affects paraoxonase activity and protein levels in plasma. In the entire group, paraoxonase activity was related to arylesterase activity and genotype. Whereas arylesterase activity was correlated with HDL cholesterol (HDL-C) and apolipoproteinA-I (apoA-I) levels, neither arylesterase nor paraoxonase was correlated with LPL or HL activity. Furthermore, LPL activity was positively correlated and HL inversely correlated with HDL cholesterol and apoA-I levels, whereas LPL was inversely correlated with triglyceride levels. The paraoxonase genotypes of the study group were 30 individuals homozygous for the low-activity allele, 38 heterozygotes, and 4 individuals homozygous for the high-activity allele. Paraoxonase genotype accounted for approximately .75 of the variation in paraoxonase activity. Paraoxonase activity was linearly related to arylesterase activity within each subgroup. No difference in either LPL or HL activity was seen as a function of paraoxonase genotype, nor were differences seen in plasma triglyceride or HDL-C by genotype by ANOVA. The relation between LPL and HL and components of HDL in the paraoxonase genotypic subgroups in general reflected the associations seen in the group as a whole. Multivariate analysis showed that LPL, HL, and arylesterase, a measure of paraoxonase mass, were independent predictors of HDL cholesterol, while paraoxonase genotype or activity was not. Thus, variation in LPL and HL appears to be significantly related to HDL cholesterol and apoA-I levels. The levels of HDL are a major correlate of paraoxonase protein levels, while paraoxonase genotype is the major predictor of plasma paraoxonase activity.


Assuntos
Esterases/genética , Lipase Lipoproteica/sangue , Lipoproteínas HDL/sangue , Adulto , Arildialquilfosfatase , Esterases/sangue , Feminino , Heterozigoto , Homozigoto , Humanos , Masculino , Análise Multivariada
9.
Genomics ; 35(3): 586-9, 1996 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8812495

RESUMO

Serum paraoxonase/arylesterase (PON) is an "A" esterase found in the HDL2 fraction of mammalian sera closely associated with apolipoproteins A1 and J. This enzyme hydrolyzes the active metabolites (oxons) of several organophosphate (OP) insecticides as well as the P-F bond of the nerve agents soman and sarin. PON also destroys biologically active, multioxygenated phospholipids. Two factors result in large individual variations in PON serum levels, a substrate-dependent activity polymorphism and large individual differences in PON protein levels that are stable over time. Animal model studies indicate that PON activity levels are likely to play a major role in determining sensitivity to OPs. The arg192 PON isoform appears to be a risk factor in coronary artery disease. We report here the characterization of a 28-kb contig encompassing 300 bp of 5' sequence, the entire coding region, and 2 kb of 3'-flanking sequence of the PON gene. The structural portion of the paraoxonase protein is encoded by nine exons that form the primary transcript through the use of typical splice donor and acceptor sites. DNA sequences of the regions surrounding all the coding exons have been determined. A polymorphic CA repeat is located in intron 4.


Assuntos
Esterases/genética , Arildialquilfosfatase , Sequência de Bases , DNA Complementar , Repetições de Dinucleotídeos , Éxons , Humanos , Íntrons , Dados de Sequência Molecular
10.
Arch Mal Coeur Vaiss ; 88(8): 1075-80, 1995 Aug.
Artigo em Francês | MEDLINE | ID: mdl-8572849

RESUMO

UNLABELLED: The mid frequency component (MFC = 66-128 mHz) of blood pressure is an index of sympathetic vascular control. To investigate the effect of bisoprolol (B) and ramipril (R) treatment (TT) on the short-term variability of systolic blood pressure (SBP) diastolic blood pressure (DPB) and heart rate (HR) reactivity during mental stress, we studied 54 mild essential untreated hypertensive patients (24 men, 45 +/- 9.6 years, BP > 160/90 mmHg after a 15-days placebo run-in period) who were randomly assigned to double blind treatment (B: 10 mg/day: n = 28 and R: 5 mg/day: n = 26). A Stroop Word Color Conflict Test (SWCCT) was performed before and after 2 months of treatment. Hemodynamic parameters (BP and HR) were measured by a non invasive device (Finapres 2300E, Ohmeda-Maurepas) and underwent spectral analysis (SBP: mmHg.Hz-1/2, HR: beats/min.Hz-1/2, Anapres 1.2, Notocord-Orgametrie Systems, Igny-Lille) at rest and during SWCCT. The sympathetic vascular activity was assessed by calculating the area of the mid-frequency component (MFC = 66-128 Hz). RESULTS: [table: see text] CONCLUSION: The absolute variations in sympathetic activity during SWCCT as demonstrated by analysis of MFC of SBP and HR is not affected by chronic ramipril treatment, whereas bisoprolol attenuates sympathetic reactivity during SWCCT.


Assuntos
Anti-Hipertensivos/farmacologia , Bisoprolol/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ramipril/farmacologia , Estresse Psicológico , Adulto , Anti-Hipertensivos/uso terapêutico , Bisoprolol/uso terapêutico , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Placebos , Estudos Prospectivos , Testes Psicológicos , Ramipril/uso terapêutico , Processamento de Sinais Assistido por Computador , Análise Espectral , Estresse Psicológico/fisiopatologia , Fatores de Tempo
11.
Arch Mal Coeur Vaiss ; 87(8): 1073-7, 1994 Aug.
Artigo em Francês | MEDLINE | ID: mdl-7755462

RESUMO

OBJECTIVES: To study the modifications of the BP and its short-term variability in hypertensives patients submitted at to a psychological stress test. DESIGN AND METHODS: Fourty nine hypertensive subjects (27 women and 22 men, aged 46 +/- 9, SBP 164 +/- 10, DBP 97 +/- 6 mmHg after a 15 days placebo run-in period) were studied. We used the original version of Stroop Word Color Conflict Test (SWCCT) to induce mental stress. Haemodynamic parameters (SBP, DBP, MPB and HR) were measured continuously by a non invasive method (Finapres) with data acquisition every 0.5 second allowing spectral analysis of SBP variability at rest, during and after SWCCT (FFT algorithm on 256 point time series Anapres 1.2). RESULTS: All haemodynamic parameters increased during stress test (p = 0.001). The mean value and the variability (V) of SBP standard deviation (SD) increased during SWCCT (p = 0.001 and p = 0.003 respectively). Two minutes after the test, SPB returned to the rest level, while the overall variability of SPB remained elevated (p = 0.007). Spectral analysis: the total area under the curve and the mid frequency component (MFC) (66-128 mHz) increased during and after SWCCT (p = 0.001). [table: see text] CONCLUSION: Short-term variability of SBP is increased in hypertensives when submitted to a SWCCT appears to induce sustained orthosympathetic stimulation as suggested by the increase of mid frequency component (Mayer waves).


Assuntos
Pressão Sanguínea , Hipertensão/fisiopatologia , Estresse Psicológico , Adulto , Idoso , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Testes Psicológicos , Descanso , Análise Espectral
12.
Arch Mal Coeur Vaiss ; 87(8): 1097-101, 1994 Aug.
Artigo em Francês | MEDLINE | ID: mdl-7755467

RESUMO

UNLABELLED: In order to determine the different ways the hypertensives' blood pressure would react during mental stress, 49 patients, 27 women and 22 men, were submitted at the Stroop Word Colour Conflict Test. Their haemodynamic parameters were recorded by finger photoplethysmography (Finapres device), with equidistant sampling (2 Hz). Temporal and spectral analysis showed evidence of: a quick and short elevation of BP and HR and a greater variability of SBP, as shown by the increase of the MF (66-128 mHZ) module. Patients can be divided into 3 clusters according to the reactivity of SBP. Group I (N, mean +/- sigma) 13, + 32.7 +/- 8 mmHg; group II 24, + 10.3 +/- 6; group III 12, -10.2 +/- 7. They were comparable on anxiety level and on any demographic and clinical feature. In group III, the higher NA at rest, the bigger the fall of SBP when stressed. The cognitive efficiency of these patients is increased by stress. Spectral analysis: Mid frequency (66-128 mHz) components are markedly higher in group III, before, during and after SWCCT showing a higher sympathetic tonus. CONCLUSION: The reactivity of BP is not homogeneous. One fourth of our patients showed a decrease of SBP during the cognitive treatment stage of the test without showing a decrease of sympathetic tone. Anxiety level is not predictive of BP's response.


Assuntos
Hipertensão/fisiopatologia , Estresse Psicológico , Adulto , Idoso , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Processamento de Sinais Assistido por Computador , Sistema Nervoso Simpático/fisiopatologia
13.
Biopolymers ; 33(11): 1725-45, 1993 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8241430

RESUMO

The effects of inserting 16 base pair (bp) of alternating CG [(CG)8] near the middle of a much longer restriction fragment (1097 bp) are investigated by measuring various properties that are sensitive to secondary and tertiary structure. Results for this fragment are compared with those for a control fragment (1089 bp) with the identical sequence except at the insert. Another fragment (1382 bp), which contains a 296-bp extension at the 5'-end of the 1089-bp control fragment, is also used as a secondary control in some experiments. When the 1097-bp (CG)8 insert fragment is compared with the control fragments in 0.1 M NaCl buffer, the (CG)8 insert is found to induce disproportionately large relative changes in the molar ellipticity at 273 nm ([theta]273), the torsion constant (alpha) measured by fluorescence polarization anisotropy, the optical melting profile, and the susceptibility to S1 nuclease. Estimates of the minimum distance over which the (CG)8 insert alters the secondary structure range from 330 to 550 bp. With increasing NaCl concentration, the 1097-bp insert fragment undergoes a structural transition between 2.0 and 2.5 M that is manifested in the apparent diffusion coefficient (Dplat) from dynamic light scattering at large scattering vector. This transition, which is not exhibited by the control DNAs, is presumed to involve formation of Z-helix at the insert. However, the observed decrease in (Dplat) is attributed to an increase in bending rigidity, which perforce must be globally distributed far beyond the (CG)8 insert per se. In 4.25 M NaCl (but not in 0.1 M NaCl), the addition of 1 ethidium dye per 300 bp induces an extensive structural transition in the 1097 bp (CG)8 insert fragment. This transition, which also is not exhibited by the control DNAs, significantly decreases the bending rigidity, doubles [theta]273, and takes place on a time scale of a few days. Removal of ethidium and salt by dialysis vs 0.1 M NaCl buffer restores the original properties of the 1097-bp (CG)8 insert fragment. The present results are consistent with a (fluctuating, long-range) description of the secondary structure in which a given short sequence transiently fluctuates among two or more distinct secondary structures that extend over much larger domains of variable position and size, and whose relative stabilities depend on distant as well as close-lying base pairs.


Assuntos
Citosina/química , DNA/química , Guanina/química , Conformação de Ácido Nucleico , Composição de Bases , Sequência de Bases , Dados de Sequência Molecular , Estrutura Molecular , Termodinâmica
14.
Nat Genet ; 3(1): 73-6, 1993 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8098250

RESUMO

The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at position 192 specifies high activity PON whereas a glutamine specifies the low activity variant. Allele-specific probes or restriction enzyme analysis of amplified DNA allow for the genotyping of individuals. PON maps to chromosome 7q21-22, proximal to the cystic fibrosis gene, in agreement with previous genetic linkage studies.


Assuntos
Paraoxon , Monoéster Fosfórico Hidrolases/genética , Arildialquilfosfatase , Sequência de Bases , Cromossomos Humanos Par 7 , Clonagem Molecular , DNA , Humanos , Dados de Sequência Molecular , Monoéster Fosfórico Hidrolases/sangue , Polimorfismo de Fragmento de Restrição
15.
Biochemistry ; 30(42): 10141-9, 1991 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-1657140

RESUMO

Serum paraoxonase hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. High serum paraoxonase levels appear to protect against the neurotoxic effects of organophosphorus substrates of this enzyme [Costa et al. (1990) Toxicol. Appl. Pharmacol. 103, 66-76]. The amino acid sequence accounting for 42% of rabbit paraoxonase was determined by (1) gas-phase sequencing of the intact protein and (2) peptide fragments from lysine and arginine digests. From these data, two oligonucleotide probes were synthesized and used to screen a rabbit liver cDNA library. A clone was isolated and sequenced, and contained a 1294-bp insert encoding an open reading frame of 359 amino acids. Northern blot hybridization with RNA isolated from various rabbit tissues indicated that paraoxonase mRNA is synthesized predominately, if not exclusively, in the liver. Southern blot experiments suggested that rabbit paraoxonase is coded by a single gene and is not a family member of closely related genes. Human paraoxonase clones were isolated from a liver cDNA library by using the rabbit cDNA as a hybridization probe. Inserts from three of the longest clones were sequenced, and one full-length clone contained an open reading frame encoding 355 amino acids, four less than the rabbit paraoxonase protein. Each of the human clones appeared to be polyadenylated at a different site, consistent with the absence of the canonical polyadenylation signal sequence. Of potential significance with respect to the paraoxonase polymorphism, the derived amino acid sequence from one of the partial human cDNA clones differed at two positions from the full-length clone. Amino-terminal sequences derived from purified rabbit and human paraoxonase proteins suggested that the signal sequence is retained, with the exception of the initiator methionine residue [Furlong et al. (1991) Biochemistry (preceding paper in this issue)]. Characterization of the rabbit and human paraoxonase cDNA clones confirms that the signal sequences are not processed, except for the N-terminal methionine residue. The rabbit and human cDNA clones demonstrate striking nucleotide and deduced amino acid similarities (greater than 85%), suggesting an important metabolic role and constraints on the evolution of this protein.


Assuntos
DNA/isolamento & purificação , Monoéster Fosfórico Hidrolases/sangue , Monoéster Fosfórico Hidrolases/genética , Sinais Direcionadores de Proteínas/genética , Adulto , Sequência de Aminoácidos , Animais , Arildialquilfosfatase , Sequência de Bases , Clonagem Molecular , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Dados de Sequência Molecular , Fragmentos de Peptídeos/isolamento & purificação , Monoéster Fosfórico Hidrolases/isolamento & purificação , Sinais Direcionadores de Proteínas/sangue , Sinais Direcionadores de Proteínas/isolamento & purificação , RNA Mensageiro/análise , Coelhos , Alinhamento de Sequência
16.
Percept Psychophys ; 46(5): 434-42, 1989 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-2813028

RESUMO

When a theoretical psychometric function is fitted to experimental data (as in the obtaining of a psychophysical threshold), maximum-likelihood or probit methods are generally used. In the present paper, the behavior of these curve-fitting methods is studied for the special case of forced-choice experiments, in which the probability of a subject's making a correct response by chance is not zero. A mathematical investigation of the variance of the threshold and slope estimators shows that, in this case, the accuracy of the methods is much worse, and their sensitivity to the way data are sampled is greater, than in the case in which chance level is zero. Further, Monte Carlo simulations show that, in practical situations in which only a finite number of observations are made, the mean threshold and slope estimates are significantly biased. The amount of bias depends on the curve-fitting method and on the range of intensity values, but it is always greater in forced-choice situations than when chance level is zero.


Assuntos
Comportamento de Escolha , Aprendizagem por Probabilidade , Psicometria , Humanos , Método de Monte Carlo , Viés de Seleção
17.
J Bacteriol ; 171(3): 1435-44, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2522090

RESUMO

A strain of Escherichia coli which was derived from a gentamicin-resistant clinical isolate was found to be cross-resistant to neomycin and streptomycin. The molecular nature of the genetic defect was found to be an insertion of two GC base pairs in the uncG gene of the mutant. The insertion led to the production of a truncated gamma subunit of 247 amino acids in length instead of the 286 amino acids that are present in the normal gamma subunit. A plasmid which carried the ATP synthase genes from the mutant produced resistance to aminoglycoside antibiotics when it was introduced into a strain with a chromosomal deletion of the ATP synthase genes. Removal of the genes coding for the beta and epsilon subunits abolished antibiotic resistance coded by the mutant plasmid. The relationship between antibiotic resistance and the gamma subunit was investigated by testing the antibiotic resistance of plasmids carrying various combinations of unc genes. The presence of genes for the F0 portion of the ATP synthase in the presence or absence of genes for the gamma subunit was not sufficient to cause antibiotic resistance. alpha, beta, and truncated gamma subunits were detected on washed membranes of the mutant by immunoblotting. The first 247 amino acid residues of the gamma subunit may be sufficient to allow its association with other F1 subunits in such a way that the proton gate of F0 is held open by the mutant F1.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/enzimologia , ATPases Translocadoras de Prótons/genética , Sequência de Aminoácidos , Aminoglicosídeos , Sequência de Bases , Resistência Microbiana a Medicamentos , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Genes , Genes Bacterianos , Genótipo , Substâncias Macromoleculares , Dados de Sequência Molecular , Plasmídeos , Especificidade da Espécie
18.
J Clin Endocrinol Metab ; 64(1): 27-31, 1987 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3782434

RESUMO

The purpose of this study was to determine whether plasma oxytocin (OT) levels change during human sexual responses and, if so, to demonstrate the temporal pattern of change. Plasma OT levels were measured by RIA before, during, and after private self-stimulation to orgasm in normal men (n = 9) and women (n = 13). Blood samples were collected continuously through indwelling venous catheters. The subjects pressed a signal to indicate the start and finish of orgasm/ejaculation. Objective assessment of sexual arousal and orgasm was obtained by measuring blood-pulse amplitude and electromyographic activity, recorded continuously throughout testing from an anal device containing a photoplethysmograph and electromyograph electrodes connected to a polygraph located in an adjacent room. These measures allowed collection of data from men and women of changes in blood flow and muscle activity in the lower pelvic/pubic area. Plasma OT levels increased during sexual arousal in both women and men and were significantly higher during orgasm/ejaculation than during prior baseline testing. We suggest that the temporal pattern of secretion could be related to smooth muscle contractions of the reproductive system during orgasm.


Assuntos
Ejaculação , Orgasmo , Ocitocina/sangue , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular , Músculo Liso/fisiologia , Pelve/irrigação sanguínea , Pelve/fisiologia , Pulso Arterial , Radioimunoensaio , Fluxo Sanguíneo Regional
19.
J Bacteriol ; 153(1): 416-22, 1983 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-6294057

RESUMO

Plasmids carrying cloned segments of the unc operon of Escherichia coli have been used in genetic complementation analyses to identify three independent mutants defective in the uncH gene, which codes for the delta subunit of the ATP synthetase. Mutations in other unc genes have also been mapped by this technique. ATPase activity was present in extracts of the uncH mutants, but the enzyme was not as tightly bound to the membrane as it was in the parental strain. ATP-dependent membrane energization was absent in membranes isolated from the uncH mutants and could not be restored by adding normal F1 ATPase from the wild-type strain. F1 ATPase prepared from uncH mutants could not restore ATP-dependent membrane energization when added to wild-type membranes depleted of F1. Membranes of the uncH mutants were not rendered proton permeable as a result of washing with low-ionic-strength buffer.


Assuntos
Escherichia coli/genética , Genes , Complexos Multienzimáticos/genética , Fosfotransferases/genética , Complexos de ATP Sintetase , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Membrana Celular/enzimologia , Escherichia coli/enzimologia , Teste de Complementação Genética , Mutação , NAD/metabolismo , Plasmídeos
20.
J Parasitol ; 67(2): 191-5, 1981 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7241279

RESUMO

By injection into mice we assessed the potential for full development and oviposition of young schistosomules, juveniles, and paired adults of Schistosoma mansoni, all grown in vitro from cercariae. Schistosomules 2-hr or 13-days-old were injected into mice via the tail vein; older worms were implanted surgically into the ileocolic vein. Also implanted were previously ovigerous adult pairs that had been perfused from mice and maintained in culture up to 53 days. Eventually, all were capable of producing viable eggs except the worm-pairs that had been grown to the adult stage in vitro; these failed to grow or develop further when implanted into mice. We concluded that pairs once mature in vivo could regain the capacity for oviposition even after prolonged maintenance in vitro, but worms grown entirely in vitro to pairing may have missed some required stimulus which cannot be furnished later, even by an adequate animal host.


Assuntos
Veias Mesentéricas/parasitologia , Oviposição , Parasitologia/métodos , Schistosoma mansoni/crescimento & desenvolvimento , Animais , Biomphalaria/parasitologia , Feminino , Masculino , Camundongos , Óvulo/fisiologia , Schistosoma mansoni/anatomia & histologia , Schistosoma mansoni/fisiologia
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