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1.
Opt Express ; 22(15): 18579-87, 2014 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-25089477

RESUMO

It is well known that defects, such as holes, inside an infinite photonic crystal can sustain localized resonant modes whose frequencies fall within a forbidden band. Here we prove that finite, defect-free photonic crystals behave as mirrorless resonant cavities for frequencies within but near the edges of an allowed band, regardless of the shape of their outer boundary. The resonant modes are extended, surface-avoiding (nearly-Dirichlet) states that may lie inside or outside the light cone. Independent of the dimensionality, quality factors and finesses are on the order of, respectively, (L/λ)3 and L/λ, where λ is the vacuum wavelength and L >> λ is a typical size of the crystal. Similar topological modes exist in conventional Fabry-Pérot resonators, and in plasmonic media at frequencies just above those at which the refractive index vanishes.

2.
Phys Rev Lett ; 113(2): 027402, 2014 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-25062229

RESUMO

Three-dimensional multicomponent plasmas composed of species with very different masses support a new branch of charge-density fluctuations known as acoustic plasmons. Here, we report on an ultrafast optical method to generate and probe coherent states of acoustic plasmons in a slab of GaAs, which relies on strong photoexcitation to create a large population of light electrons and heavy holes. Consistent with the random-phase-approximation theory, the data reveal standing plasma waves confined to these slabs, similar to those of conventional sound but with associated velocities that are significantly larger.

3.
Phys Rev Lett ; 108(14): 140405, 2012 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-22540776

RESUMO

We show that the pseudorelativistic physics of graphene near the Fermi level can be extended to three dimensional (3D) materials. Unlike in phase transitions from inversion symmetric topological to normal insulators, we show that particular space groups also allow 3D Dirac points as symmetry protected degeneracies. We provide criteria necessary to identify these groups and, as an example, present ab initio calculations of ß-cristobalite BiO(2) which exhibits three Dirac points at the Fermi level. We find that ß-cristobalite BiO(2) is metastable, so it can be physically realized as a 3D analog to graphene.

4.
J Exp Med ; 169(5): 1565-81, 1989 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-2523952

RESUMO

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.


Assuntos
Esterases/genética , Hipersensibilidade Tardia , Interferon gama/genética , Hanseníase/imunologia , Hibridização de Ácido Nucleico , RNA Mensageiro/análise , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Hanseníase/patologia , Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
5.
Oncogene ; 11(6): 1179-89, 1995 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-7566979

RESUMO

Defects in cellular differentiation are a common occurrence in human cancers. The combination of recombinant human fibroblast interferon (IFN-beta) and the antileukemic compound mezerein (MEZ) results in an irreversible loss of proliferative capacity and terminal cell differentiation in H0-1 human melanoma cells. In contrast, either agent alone induces reversible growth arrest and/or specific components of the differentiation process without inducing terminal differentiation. The current study investigates changes in cell cycle, cell cycle gene expression and E2F transcription factor complex formation during the processes of reversible and irreversible (terminal) differentiation. Induction of both terminal differentiation and reversible differentiation (MEZ treatment) results in a temporal decrease in DNA synthesis and the percentage of cells in S phase and a decrease in the expression of cell cycle and growth regulated genes, including cdc2, cyclin A, cyclin B, histone H1, histone H4, nm23-H1, p53 and c-myc. Persistent gene expression changes occur in terminally differentiated cells, but not in reversibly differentiated cells. H0-1 cells contain several E2F binding activities, including uncomplexed E2F, an E2F-p107-cyclin A-cdk2 kinase complex and an Rb-E2F complex. Induction of growth arrest by MEZ results in a slow migrating gelshift band that contains E2F associated with the pRb2/p130 protein. There is also a loss of the Rb-E2F complex. Induction of terminal differentiation after treatment with IFN-beta + MEZ generates a second pRb2/p130-E2F complex that migrates considerably faster than the pRb2/p130-E2F complex resulting from growth arrest. The slower migrating complex may contribute to growth arrest, whereas the faster migrating complex may play a role in terminal differentiation. Our results demonstrate that terminal cell differentiation involves a co-ordinate and continuous suppression of a number of cell cycle and growth related genes and results in the development of a novel E2F transcription factor complex not apparent in growth arrested and reversibly differentiated human melanoma cells.


Assuntos
Proteínas de Transporte , Proteínas de Ciclo Celular , Ciclinas/genética , Proteínas de Ligação a DNA , Diterpenos , Regulação Neoplásica da Expressão Gênica , Histonas/genética , Melanoma/patologia , Fatores de Transcrição/biossíntese , Proteína Quinase CDC2/genética , Ciclo Celular , Diferenciação Celular , Divisão Celular , DNA/biossíntese , Fatores de Transcrição E2F , Humanos , Interferon beta/farmacologia , Melanoma/metabolismo , Antígeno Nuclear de Célula em Proliferação/análise , Proteína 1 de Ligação ao Retinoblastoma , Terpenos/farmacologia , Fator de Transcrição DP1 , Células Tumorais Cultivadas
6.
Hypertension ; 25(6): 1322-5, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7768581

RESUMO

The prevalence of hypertension is particularly high in people of black African descent throughout the world, and the consequences of hypertension, such as hypertensive heart and renal disease and stroke, are also more common. But there is little consensus on whether hypertensive retinopathy follows a similar pattern. We determined the prevalence of hypertensive retinopathy and its relationships with resting and ambulatory blood pressure in a population study of Afro-Caribbeans and Europeans aged 40 to 64 years in London, UK. Retinal photographs of 651 participants were graded for hypertensive retinopathy. Age- and sex-standardized prevalence of retinopathy was 11% (95% confidence interval, 8% to 14%) in Europeans and 21% (95% confidence interval, 16% to 26%) in Afro-Caribbeans (P < .001), respectively. This ethnic difference in prevalence was greatest in normotensive women (8% in Europeans versus 20% in Afro-Caribbeans, P < .001). Resting systolic pressure was 8 mm Hg higher in normotensive Afro-Carribean compared with European women, but this could not fully account for the ethnic difference in the prevalence of retinopathy. Examination of the different relationships of age and resting and ambulatory blood pressures with hypertensive retinopathy showed that these relationships were strongest in European women and weakest in Afro-Caribbean women. We conclude that hypertensive retinopathy is more common in Afro-Caribbeans, particularly women, and that ethnic differences in resting blood pressure cannot fully account for this. The relatively weak relationship between resting and ambulatory blood pressures and retinopathy in Afro-Caribbeans suggests that factors other than blood pressure determine the high rates of hypertensive retinopathy in this group.


Assuntos
Hipertensão/complicações , Doenças Retinianas/epidemiologia , Adulto , Fatores Etários , População Negra , Região do Caribe/etnologia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças Retinianas/etiologia , Fatores de Risco , Reino Unido/epidemiologia , População Branca
7.
Pediatrics ; 95(6): 883-7, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7761215

RESUMO

BACKGROUND: Intravenous (i.v.) hydrocortisone (HC) has been used recently in selected preterm infants for hypotension soon after birth. During the same time period that HC was used, there was a marked increase in the incidence of disseminated candidal infections (DCIs). OBJECTIVE: To determine whether there is an association between DCI in the first 35 days of life and i.v. HC in preterm infants. RESEARCH DESIGN: A hospital case-control study comparing the exposure of HC between preterm infants with DCI and matched infants without DCI. SETTING: A tertiary level intensive care nursery in a major teaching hospital in San Francisco, CA. PATIENTS: Seventeen preterm infants with DCI and 25 infants without DCI, with gestational age younger than 28 weeks and birth weight less than 1000 g, inborn and outborn admitted to the intensive care nursery between January 1992 and September 1993. METHODS: All preterm infants diagnosed with DCI at younger than 35 days of age were identified using a perinatal and neonatal database. DCI was defined as a blood, cerebrospinal fluid, or two urine cultures positive for Candida requiring antifungal therapy. A control group of uninfected infants matched for the major risk factors for DCI (gestational age, birth weight, duration of intubation, broad-spectrum antibiotics, and i.v. alimentation, including lipids and central venous catheters) admitted during the same period was identified using the same database. Postmatching comparison was performed for several other factors to detect any other differences between the groups. RESULTS: The infants with DCI (n = 17) and control infants (n = 25) had no statistical difference in exposure to the major risk factors for DCI or in postmatching comparison. Ten (59%) of the infants with DCI were receiving HC at the time of infection, whereas four (16%) of the control infants received HC during the first 35 days of life. Infants with DCI were 7.5 times as likely as control infants (95% confidence interval, 5 to 11) to have received IV HC before the onset of fungal infection. CONCLUSION: We conclude that the administration of i.v. HC significantly increases the risk of DCI in susceptible preterm infants younger than 35 days of age. The potentially serious risks of DCI should be considered particularly in the patient selection process for administration of i.v. HC.


Assuntos
Candidíase/etiologia , Hidrocortisona/efeitos adversos , Doenças do Prematuro/etiologia , Estudos de Casos e Controles , Humanos , Hidrocortisona/uso terapêutico , Hipotensão/tratamento farmacológico , Recém-Nascido , Recém-Nascido Prematuro , Infusões Intravenosas , Fatores de Risco
8.
Chest ; 102(2): 428-32, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1643927

RESUMO

Adjunctive corticosteroid therapy is recommended for selected human immunodeficiency virus (HIV)-infected patients with presumed Pneumocystis carinii pneumonia. Because corticosteroids may exacerbate undiagnosed tuberculosis, we evaluated the frequency with which tuberculosis in HIV-infected patients mimics P carinii pneumonia. Over a 12-month period, we identified 105 HIV-infected patients with pleuropulmonary tuberculosis and 84 patients with P carinii pneumonia who were sufficiently hypoxemic to warrant corticosteroid therapy. Of the 105 patients with tuberculosis, acid-fast smears of clinical samples were positive in 49 cases, and chest roentgenographic findings suggested tuberculosis in an additional 44 cases. The 12 patients with negative acid-fast smears and nonspecific chest roentgenographic findings presented a potential diagnostic dilemma between tuberculosis and P carinii pneumonia. Pneumocystis carinii pneumonia should not have been a presumptive diagnosis of eight of these 12 patients because of absence of pulmonary symptoms and chest roentgenographic abnormalities (four cases), a CD4 count greater than 500/cu mm (three cases), or marked lymphadenopathy suggestive of tuberculosis (one case). Thus, only 4 percent (4/105) of HIV-infected patients with pleuropulmonary tuberculosis had clinical and chest roentgenographic features mimicking P carinii pneumonia. Two of these four patients were sufficiently hypoxemic to warrant corticosteroid therapy. Thus, if corticosteroids had been routinely used during the study period, 84 patients with P carinii pneumonia would have been treated, including two patients with undiagnosed tuberculosis. We conclude that the use of corticosteroids for presumed P carinii pneumonia carries a small but acceptable risk of inadvertent exacerbation of tuberculosis, provided clinical and chest roentgenographic features do not suggest tuberculosis.


Assuntos
Infecções por HIV/diagnóstico , HIV-1 , Infecções Oportunistas/diagnóstico , Pneumonia por Pneumocystis/diagnóstico , Tuberculose Pulmonar/diagnóstico , Corticosteroides/uso terapêutico , Diagnóstico Diferencial , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Mycobacterium tuberculosis/isolamento & purificação , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Pneumocystis/isolamento & purificação , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Radiografia , Tuberculose Pleural/complicações , Tuberculose Pleural/diagnóstico , Tuberculose Pulmonar/complicações
9.
Int J STD AIDS ; 5(5): 318-21; discussion 322-6, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7819348

RESUMO

We sought to ascertain general practitioners' (GPs) views on their patients' attendances at genitourinary medicine (GUM) departments regarding methods of referral, record keeping and supplying of information to insurance companies. A questionnaire was sent to 429 local GPs of whom 294 (68%) responded. A written means of referral was less likely for HIV than for sexually transmitted disease (STD) (P < 0.001), and in turn less likely for STD than for other genital problems (P < 0.02). The percentage of GPs who did not keep a record of referrals were: For HIV testing--29%; STDs--13%; and for other genital problems--8%. Whilst 48% of GPs did not feel obliged to divulge lifestyle information on a patient, 21% would feel it necessary to confirm that a patient had suffered from an STD if the 'source' on a cytology smear was shown to be that of a GUM department. Only 23 GPs (8%) felt they had sufficient knowledge as to the use to which the information they supplied to insurance companies was put. Many GPs acknowledged that their practice, with reference to patient attendance at a GUM department, was influenced by life insurance considerations. Bearing in mind the current policy of The Association of British Insurers which recommends that all applicants for life insurance be asked to declare any previous STD and counselling/testing for HIV, we make several suggestions which may aid GPs in this difficult area.


Assuntos
Confidencialidade , Revelação , Medicina de Família e Comunidade/organização & administração , Seguro de Vida , Infecções Sexualmente Transmissíveis/diagnóstico , Atitude do Pessoal de Saúde , Controle de Formulários e Registros , Humanos , Estilo de Vida , Padrões de Prática Médica , Encaminhamento e Consulta , Infecções Sexualmente Transmissíveis/etiologia , Inquéritos e Questionários , Reino Unido
10.
Int J STD AIDS ; 4(5): 297-9, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8218518

RESUMO

A retrospective study compared one year's cervical smear results from 4920 women from the following 3 populations in Leicestershire; the Genitourinary Medicine (GUM) Departments; the city family planning clinic (FPC); and a general practice (GP) in a local University town. The results were standardized for age by logistic regression. Cytological abnormality was divided into: dyskaryosis (all grades), borderline, and inflammatory changes. The GUM attenders had an excess of total cervical smear abnormalities compared to both the FPC (P < 0.001) and GP population (P < 0.001) after adjusting for age. The FPC and GP rates of smear abnormality were similar at 60 and 63 per 1000 women screened, respectively, while the rate for the GUM clinic was 155 per 1000 women screened.


Assuntos
Colo do Útero/patologia , Doenças do Colo do Útero/patologia , Adulto , Instituições de Assistência Ambulatorial , Colo do Útero/citologia , Medicina de Família e Comunidade , Feminino , Doenças Urogenitais Femininas , Humanos , Prevalência , Estudos Retrospectivos , Reino Unido/epidemiologia , Doenças do Colo do Útero/epidemiologia , Esfregaço Vaginal
11.
Int J STD AIDS ; 7(7): 480-4, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9116063

RESUMO

One hundred and fifty women who attended the routine genitourinary medicine (GUM) clinic at the Leicester Royal Infirmary (LRI) between August 1993 and February 1994 completed a questionnaire enquiring into a past history of sexual assault. Of these, 52 (34.7%) confirmed that they had been assaulted previously, 18 below the age of 16, 22 after this age and 12 in both age groups. Non penetrative abuse was most common in those violated as minors and vaginal penetration in women assaulted over the age of 16. The strongest demographic indicator for sexual abuse among this study group was that of a current divorced/separated marital status. Assailants of minors were most likely to be someone known to the family whereas male intimates accounted for a third of assaults on older women. Sexual dysfunction was acknowledged by approximately half of those previously assaulted as a sequelae of abuse. It is important that GUM physicians remain alert for sequelae of sexual abuse and offer services appropriate to the victim's needs.


Assuntos
Doenças Urogenitais Femininas/etiologia , Doenças Urogenitais Masculinas , Estupro , Adolescente , Adulto , Criança , Feminino , Doenças Urogenitais Femininas/epidemiologia , Humanos , Masculino , Prevalência , Inquéritos e Questionários
12.
Int J STD AIDS ; 6(2): 95-100, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7779938

RESUMO

One-hundred-and-fifty male patients who attended the department of genitourinary medicine (GUM) completed a questionnaire which enquired into a past history of sexual assault and asked certain details about the assault and various sequelae of such an experience. Twenty-one men gave a history of sexual assault, 11 of whom had been abused before the age of 16, 7 afterwards and 3 in both age groups. Victims of such an assault were more likely to be homosexual or bisexual than heterosexual. The substantial majority i.e. 104 (81%) of the 129 patients who had not been assaulted in the past had been brought up by both natural parents. However, of the 21 males who reported a history of previous sexual abuse only 11 (52%) had been raised by both natural parents alone and 9 of the remaining 10 who divulged such information had been brought up in other circumstances. The association between not being raised entirely by both natural parents and a history of previous sexual assault was significant (P < 0.01). Overall, physical contact of a sexual nature was the most commonly reported type of abuse, followed by anal and then by oral penetration. All of the perpetrators of assault were male except in one instance. Only 3 cases of assault were reported to the police or other agencies. Those who had been abused as minors were more likely to acknowledge subsequent psychological difficulties and to have obtained professional counselling. This problem is a significant one which goes largely undetected in GUM departments and elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Estupro/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Criança , Unidades Hospitalares , Humanos , Masculino , Doenças Urogenitais Masculinas , Saúde Mental , Pessoa de Meia-Idade , Distribuição Aleatória , Estupro/psicologia
13.
BMJ ; 297(6657): 1155-9, 1988 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-3144329

RESUMO

STUDY OBJECTIVE: To compare responses of blood pressure to the calcium antagonist verapamil and the beta blocker metoprolol in black compared with white diabetics with hypertension and to monitor urinary albumin excretion in relation to fall in blood pressure. DESIGN: Double blind, placebo controlled, random order crossover trial with four week placebo run in period and two six week active phases separated by a two week placebo washout period. SETTING: Outpatient department of a general hospital in a multiethnic health department. Patients--Diabetic patients with hypertension. Four dropped out before randomisation; 25 black and 14 white patients completed the trial. INTERVENTIONS: Patients given slow release verapamil 120 mg or 240 mg twice daily with placebo or metoprolol 50 mg or 100 mg twice daily with placebo. Treatment for diabetes (diet alone or with oral hypoglycaemic drugs) remained unchanged. END POINT: Comparison of changes in blood pressure in the two groups taking both drugs. MEASUREMENTS AND MAIN RESULTS: Metoprolol had little effect on blood pressure in black patients (mean fall 4.0 mm Hg systolic (95% confidence interval -2.5 to 10.4 mm Hg), 4.3 mm Hg diastolic (-0.8 to 9.5)) but more effect in white patients (mean falls 13.4 mm Hg (0.1 to 26.7) and 10.6 mm Hg (4.5 to 16.7) respectively). Verapamil was more effective in both groups, with mean falls of 8.8 mm Hg (2.4 to 15.0) and 8.1 mm Hg (5.0 to 11.2) in black patients and 19.1 mm Hg (5.4 to 32.9) and 11.4 mm Hg (0.9 to 22.0) in white patients. Heart fate fell significantly in black patients taking metoprolol, which suggested compliance with treatment. Metabolic variables were unaltered by either treatment. Plasma renin activity was low in both groups after metoprolol treatment, but change in blood pressure could not be predicted from baseline plasma renin activity. Urinary albumin:creatinine ratio was independently related to baseline blood pressure but not significantly changed by treatment. CONCLUSIONS: beta Blockers alone are not effective in treating hypertension in black diabetics. Verapamil is effective but less so than in white patients. As yet no ideal monotherapy exists for hypertension in black patients.


Assuntos
Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/complicações , Hipertensão/tratamento farmacológico , Metoprolol/uso terapêutico , Verapamil/uso terapêutico , Idoso , Albuminúria/complicações , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Renina/sangue
16.
Dentomaxillofac Radiol ; 38(7): 445-51, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19767514

RESUMO

OBJECTIVES: Conventional radiographic imaging of teeth underestimates the presence of caries. The objective of this study was to compare the efficacy of high-resolution cone beam CT (CBCT) images and conventional charge-coupled device (CCD) images for detecting proximal and occlusal caries. METHODS: Non-restored, extracted human permanent premolar and molar teeth were mounted and then imaged with a 3DX Accuitomo and a CCD. We selected 92 occlusal and 100 proximal surfaces for raters to score. Of these, 36 and 25, respectively, had lesions extending into dentin. Using a five-step confidence scale, eight practising dentists evaluated the images for the presence of caries in dentin using both modalities. Actual presence and extent of caries was established with microCT imaging. RESULTS: For proximal surface lesions extending into dentin, the average sensitivity score using 3DX images (0.61) was almost twice that of CCD images (0.33) and the difference was significant. The specificity values for both systems were high and not significantly different from each other. For occlusal surfaces, raters detected significantly more lesions in the enamel or dentin when using the 3DX images than when using CCD images. However, the raters also had significantly lower average specificity scores for the 3DX images compared with the CCD images for lesions at both depths. CONCLUSIONS: Practising dentists were able to improve their detection of proximal-surface caries extending into the dentin, but not occlusal caries, using 3DX high-resolution cone beam CT images compared with CCD images.


Assuntos
Tomografia Computadorizada de Feixe Cônico/normas , Cárie Dentária/diagnóstico por imagem , Radiografia Dentária Digital/normas , Tomografia Computadorizada de Feixe Cônico/instrumentação , Humanos , Radiografia Dentária Digital/instrumentação , Sensibilidade e Especificidade , Extração Dentária
17.
Leukemia ; 23(4): 729-38, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19151789

RESUMO

The tumor suppressor Gadd45alpha was earlier shown to be a repressed target of sustained receptor-mediated ERK1/2 signaling. We have identified Gadd45alpha as a downregulated gene in response to constitutive signaling from two FLT3 mutants (FLT3-ITD and FLT3-TKD) commonly found in AML, and a leukemogenic GM-CSF receptor trans-membrane mutant (GMR-V449E). GADD45A mRNA downregulation is also associated with FLT3-ITD(+) AML. Sustained ERK1/2 signaling contributes significantly to receptor-mediated downregulation of Gadd45alpha mRNA in FDB1 cells expressing activated receptor mutants, and in the FLT3-ITD(+) cell line MV4;11. Knockdown of Gadd45alpha with shRNA led to increased growth and survival of FDB1 cells and enforced expression of Gadd45alpha in FDB1 cells expressing FLT3-ITD or GMR-V449E resulted in reduced growth and viability. Gadd45alpha overexpression in FLT3-ITD(+) AML cell lines also resulted in reduced growth associated with increased apoptosis and G(1)/S cell cycle arrest. Overexpression of Gadd45alpha in FDB1 cells expressing GMR-V449E was sufficient to induce changes associated with myeloid differentiation suggesting Gadd45alpha downregulation contributes to the maintenance of receptor-induced myeloid differentiation block. Thus, we show that ERK1/2-mediated downregulation of Gadd45alpha by sustained receptor signaling contributes to growth, survival and arrested differentiation in AML.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Leucemia Mieloide Aguda/patologia , Mutação/fisiologia , Proteínas Nucleares/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/fisiologia , Tirosina Quinase 3 Semelhante a fms/fisiologia , Animais , Proteínas de Ciclo Celular/genética , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo/genética , Leucemia Mieloide Aguda/etiologia , Camundongos , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Nucleares/genética , RNA Mensageiro/análise , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Tirosina Quinase 3 Semelhante a fms/genética
18.
Science ; 325(5936): 64-7, 2009 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-19574385

RESUMO

The Wet Chemistry Laboratory on the Phoenix Mars Lander performed aqueous chemical analyses of martian soil from the polygon-patterned northern plains of the Vastitas Borealis. The solutions contained approximately 10 mM of dissolved salts with 0.4 to 0.6% perchlorate (ClO4) by mass leached from each sample. The remaining anions included small concentrations of chloride, bicarbonate, and possibly sulfate. Cations were dominated by Mg2+ and Na+, with small contributions from K+ and Ca2+. A moderately alkaline pH of 7.7 +/- 0.5 was measured, consistent with a carbonate-buffered solution. Samples analyzed from the surface and the excavated boundary of the approximately 5-centimeter-deep ice table showed no significant difference in soluble chemistry.


Assuntos
Ânions , Cátions , Marte , Percloratos , Fenômenos Químicos , Meio Ambiente Extraterreno , Concentração de Íons de Hidrogênio , Oxirredução , Solubilidade , Astronave , Temperatura , Água
19.
Science ; 325(5936): 61-4, 2009 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-19574384

RESUMO

Carbonates are generally products of aqueous processes and may hold important clues about the history of liquid water on the surface of Mars. Calcium carbonate (approximately 3 to 5 weight percent) has been identified in the soils around the Phoenix landing site by scanning calorimetry showing an endothermic transition beginning around 725 degrees C accompanied by evolution of carbon dioxide and by the ability of the soil to buffer pH against acid addition. Based on empirical kinetics, the amount of calcium carbonate is most consistent with formation in the past by the interaction of atmospheric carbon dioxide with liquid water films on particle surfaces.


Assuntos
Carbonato de Cálcio , Marte , Dióxido de Carbono , Precipitação Química , Meio Ambiente Extraterreno , Temperatura Alta , Concentração de Íons de Hidrogênio , Astronave , Água
20.
Ophthalmic Physiol Opt ; 25(3): 224-32, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15854069

RESUMO

INTRODUCTION: The multifocal visual-evoked potential (mfVEP) has been widely used in the study of diseases of the visual system. However, the sensitivity of the mfVEP in the objective detection of relative field defects has not been determined. This study investigates variations in mfVEP responses while simulating relative field defects by using different luminous transmission masks [neutral density (ND) filters] on the stimulus pattern. METHODS: Simulated relative field defects with four different luminous transmissions were obtained by using 0.2, 0.4, 0.6, and 0.8 ND filters, 5 degrees in size, at two different retinal eccentricities (10 and 16 degrees) on a standard mfVEP dartboard stimulus. Eleven normal subjects were recruited for mfVEP measurements. The response amplitudes and latencies of the N1 and P1 of the mfVEP, with and without small simulated relative field defects, were compared. RESULTS: The mfVEP amplitudes of N1 and P1 decreased substantially when 0.6 and 0.8 ND filters were introduced. The effects were similar at both the 10- and 16-degree eccentricities but there was no change in latency with simulated field defects at either location. CONCLUSIONS: The mfVEP can detect a simulated relative field defect 5 degrees in size starting with 0.6 log unit reduction in luminance at both 10-degree and 16-degree eccentricities. This illustrates that the sensitivity of the mfVEP measurement is nearly comparable with that of the Humphrey Visual Field Analyser.


Assuntos
Potenciais Evocados Visuais/fisiologia , Transtornos da Visão/fisiopatologia , Campos Visuais/fisiologia , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Retina/fisiopatologia , Percepção Visual/fisiologia
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