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1.
RSF ; 8(5): 184-199, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36644781

RESUMO

Education policy and the role of schools are a neglected part of the welfare state. Yet schools may be important sites for understanding how policy, work, and families intersect in immigrant households. Drawing on thirty interviews from seventeen households, this article highlights the experiences of families with young children during a time of increased national hostility toward immigrants. Given that immigrant families are often excluded from more traditional forms of social insurance, findings reveal the central role of fathers both inside and outside the home. Parental involvement, defined as parents' interactions with their children's education both inside and outside the home, was structured by English-dominant schooling environments. In Phoenix, parental involvement was uniquely shaped by a punitive immigration context at father's work and in children's schools. We discuss the implications of our findings on the intergenerational transmission of disadvantage and advance policy recommendations to support foreign- and U.S.-born children's educational success.

2.
J Racial Ethn Health Disparities ; 8(6): 1406-1414, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33098039

RESUMO

In the USA, efforts to improve unequal infant health outcomes require knowledge about how the relationship between education and infant health varies by parental gender and race/ethnicity. Drawing from a pooled random sample of over 1 million live births from the 2011 to 2017 National Vital Statistics System data, we examine the relationship between maternal and paternal education and infant health and assess how it varies by maternal racial and ethnic background. The model fit statistics suggest that the relationship between paternal education and infant health is about equal to maternal education and infant health. However, we find a weaker relationship overall between parental education and infant health among Asian and Hispanic fathers than Whites, American Indian, and Black fathers. Black fathers' education is more strongly associated with infant health than that of Black mothers. At some levels, paternal education is also more strongly related to health among Hispanic infants. The results suggest a greater focus on fathers' contributions to infant health is warranted, and programs or policies that focus on fathers could help address racial and ethnic infant health disparities.


Assuntos
Etnicidade , Saúde do Lactente , Escolaridade , Pai , Feminino , Humanos , Lactente , Masculino , População Branca
3.
SSM Popul Health ; 12: 100698, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33299927

RESUMO

Has infant health inequality narrowed or grown in recent decades? Inequality may have narrowed due to expanded medical insurance coverage and greater knowledge about fetal health. However, greater income inequality may have reduced health for births to the most economically disadvantaged mothers, leading to growing infant health inequality. We use administrative birth certificate data for over 22 million births to examine trends in inequality of infant health from 1989 to 2018 in the U.S. This period allows us to consider how contextual factors - such as passage of the Affordable Care Act, changing demographics, the Great Recession, or delayed impacts of rising income inequality - may have altered infant health inequality. We assess gaps in infant health by maternal race, marital status, and education. Following previous research, we also examine gaps between the most economically advantaged mothers - married, white mothers with a college degree - and the most economically disadvantaged mothers - single, Black mothers without a high school degree. Results reveal that inequality of infant health has increased since 2010.

4.
J Prim Prev ; 38(6): 627-645, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28866843

RESUMO

In response to U.S. federal mandates to increase the presence of underrepresented populations in prevention research, investigators have increasingly focused on using culturally sensitive research practices. However, scholars have rarely discussed these practices in terms of a larger culturally sensitive framework. Further, while the literature has explored how culturally sensitive approaches can be employed in a variety of methods, there has been little examination of how to incorporate such approaches into experimental designs. In this paper, we explain how we incorporated a culturally sensitive framework in a cluster randomized field trial with over 3000 predominantly low-income Latino families, utilizing an intervention designed to improve social relations and enhance family functioning. We offer conceptual and practical examples to guide other researchers who want to adopt a similar approach in their research designs. In addition, we discuss the benefits of forging local partnerships throughout the research process to ensure respect for racial and ethnic minorities participating in social and behavioral experimental studies. We conclude with practical considerations for utilizing a culturally sensitive framework to advance prevention programs, policies, and practices among underrepresented groups in order to achieve the ultimate goal of addressing the traditional underrepresentation of racial and ethnic minorities in research.


Assuntos
Pesquisa sobre Serviços de Saúde/organização & administração , Hispânico ou Latino/psicologia , Pobreza/etnologia , Pobreza/psicologia , Serviços Preventivos de Saúde/organização & administração , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Endoscopy ; 49(11): 1061-1068, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28898920

RESUMO

Background and study aim Different techniques have been introduced to improve the endoscopist's view and enhance the detection of polyps. The endocuff is a polymer sleeve cap that is connected to the tip of the colonoscope in order to improve visualization of the mucosa during colonoscopy. The aim of the study was to compare adenoma detection rates (ADR) of endocuff-assisted colonoscopy and conventional colonoscopy. Patients and methods Patients 50 years or older were randomized into two groups: an endocuff-assisted colonoscopy group and a conventional colonoscopy group without the endocuff. Results A total of 337 patients were included: 174 in the endocuff group and 163 in the conventional group. The median age was 61 years (interquartile range 55 - 70 years), and 74 % were women. The ADR was higher in the endocuff group than in the conventional group (22.4 % vs. 13.5 %; P = 0.02). The mean number of adenomas was 0.30 (SD 0.25) in the endocuff group and 0.21 (SD 0.26) in the conventional group (P â€Š= 0.02). The rate of ileal intubation was lower in the endocuff group (73 % vs. 87 %; P < 0.001). No serious adverse events occurred with the use of the endocuff. Conclusions Endocuff colonoscopy achieved a greater ADR than conventional colonoscopy.Trial registered at ClinicalTrials.gov (NTC02387593).


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/instrumentação , Neoplasias Colorretais/diagnóstico por imagem , Idoso , Colonoscopia/efeitos adversos , Detecção Precoce de Câncer/instrumentação , Feminino , Humanos , Íleo , Intubação Gastrointestinal , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
Early Child Res Q ; 29(4): 600-613, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25246729

RESUMO

Scholars suggest that racial/ethnic and class disparities in school-based social capital contribute to educational inequalities. Previous studies demonstrate that social capital (relations of trust, mutual expectations, and shared values) between parents and schools supports children's development. Yet we know little about the emergence of social capital, that is, the processes through which it develops. In this study, we explore mechanisms of social capital emergence in predominantly low-income Latino school communities. We draw data from an experimental study that manipulated social capital through an after-school family engagement program. Based on interviews and focus groups with participating parents, teachers, and program staff in two elementary schools, we identified four types of interactions that act as mechanisms of social capital emergence: (1) responsive communication; (2) reciprocal communication; (3) shared experiences; and (4) institutional linkage. The article connects these mechanisms to theoretically linked sources of social capital and discusses implications for theory and practice.

7.
Mol Ther ; 22(1): 196-205, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23752342

RESUMO

Respiratory syncytial virus (RSV) is a major cause of infectious lower respiratory disease in infants and the elderly. As there is no vaccine for RSV, we developed a genetic vaccine approach that induced protection of the entire respiratory tract from a single parenteral administration. The approach was based on adenovirus vectors derived from newly isolated nonhuman primate viruses with low seroprevalence. We show for the first time that a single intramuscular (IM) injection of the replication-deficient adenovirus vectors expressing the RSV fusion (F0) glycoprotein induced immune responses that protected both the lungs and noses of cotton rats and mice even at low doses and for several months postimmunization. The immune response included high titers of neutralizing antibody that were maintained ≥ 24 weeks and RSV-specific CD8+ and CD4+ T cells. The vectors were as potently immunogenic as a human adenovirus 5 vector in these two key respiratory pathogen animal models. Importantly, there was minimal alveolitis and granulocytic infiltrates in the lung, and type 2 cytokines were not produced after RSV challenge even under conditions of partial protection. Overall, this genetic vaccine is highly effective without potentiating immunopathology, and the results support development of the vaccine candidate for human testing.


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/genética , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Pulmão/imunologia , Pulmão/virologia , Camundongos , Nariz/imunologia , Nariz/virologia , Vacinas contra Vírus Sincicial Respiratório/administração & dosagem , Sigmodontinae , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas Sintéticas
8.
Virology ; 444(1-2): 119-23, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23806387

RESUMO

We have isolated and cultured three distinct adenoviruses from wild gorillas. Phylogenetic analysis grouped the viruses with human adenovirus species C based on DNA polymerase, hexon, and E4ORF6 genes. The three wild gorilla adenoviruses clustered with the other species C captive gorilla adenoviruses, forming a branch separate from human and chimpanzee/bonobo adenoviruses. Animal sera to the three newly isolated viruses did not cross-neutralize, demonstrating serological distinctiveness. The human adenovirus 5 fiber knob blocked infection, suggesting use of the Coxsackie and Adenovirus Receptor. These viruses may provide viral vectors with properties distinct from chimpanzee adenovirus and human adenovirus vectors.


Assuntos
Infecções por Adenoviridae/veterinária , Adenoviridae/classificação , Adenoviridae/genética , Doenças dos Primatas/virologia , Adenoviridae/imunologia , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/virologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Gorilla gorilla , Dados de Sequência Molecular , Testes de Neutralização , Filogenia , Análise de Sequência de DNA , Sorotipagem
9.
Infect Agent Cancer ; 8(1): 12, 2013 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-23557440

RESUMO

BACKGROUND: It has been hypothesized that human cytomegalovirus (HCMV) may be associated with breast cancer progression. However, the role of HCMV infection in breast cancer remains controversial. We aimed to assess whether HCMV genes (UL122 and UL83) could be detected in breast carcinomas and reinvestigated their possible association with breast cancer progression. DNA from paraffin-embedded tissues was analyzed by real-time PCR. We investigated 20 fibroadenomas and 27 primary breast carcinomas (stages II, III, and IV). FINDINGS: Two carcinomas were positive for HCMV, one was positive for two TaqMan viral detection probes, and one was positive for a sole TaqMan viral detection probe (UL83), whereas the remainder of the samples was negative. CONCLUSIONS: Samples studied showed no association between HCMV infection and breast cancer progression.

10.
J Phys Chem B ; 116(22): 6233-49, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22540276

RESUMO

We simulate spin relaxation processes, which may be measured by either continuous wave or pulsed magnetic resonance techniques, using trajectory-based simulation methodologies. The spin-lattice relaxation rates are extracted numerically from the relaxation simulations. The rates obtained from the numerical fitting of the relaxation curves are compared to those obtained by direct simulation from the relaxation Bloch-Wangsness-Abragam-Redfield theory (BWART). We have restricted our study to anisotropic rigid-body rotational processes, and to the chemical shift anisotropy (CSA) and a single spin-spin dipolar (END) coupling mechanisms. Examples using electron paramagnetic resonance (EPR) nitroxide and nuclear magnetic resonance (NMR) deuterium quadrupolar systems are provided. The objective is to compare those rates obtained by numerical simulations with the rates obtained by BWART. There is excellent agreement between the simulated and BWART rates for a Hamiltonian describing a single spin (an electron) interacting with the bath through the chemical shift anisotropy (CSA) mechanism undergoing anisotropic rotational diffusion. In contrast, when the Hamiltonian contains both the chemical shift anisotropy (CSA) and the spin-spin dipolar (END) mechanisms, the decay rate of a single exponential fit of the simulated spin-lattice relaxation rate is up to a factor of 0.2 smaller than that predicted by BWART. When the relaxation curves are fit to a double exponential, the slow and fast rates extracted from the decay curves bound the BWART prediction. An extended BWART theory, in the literature, includes the need for multiple relaxation rates and indicates that the multiexponential decay is due to the combined effects of direct and cross-relaxation mechanisms.


Assuntos
Simulação de Dinâmica Molecular , Anisotropia , Espectroscopia de Ressonância Magnética
11.
J Phys Chem B ; 112(42): 13359-66, 2008 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-18717543

RESUMO

Two different methods are proposed to estimate the persistence length ( P) of DNA from the measured torsion elastic constant (alpha) and the twist energy parameter ( E T ) that governs the supercoiling free energy. The first method involves Monte Carlo simulations and reversible-work calculations of E T for model DNAs that possess the measured alpha and selected trial values of P. Comparison of the computed E T values with the experimental value allows estimation of P (or equivalently the bending elastic constant (kappa beta)) by interpolation. A far simpler, though less accurate, alternative is to solve a previously conjectured analytical relation connecting E T , alpha, kappa beta (or P), and an unknown "constant" ( B). The present simulations are used to ascertain the optimum value of B and to assess the validity and accuracy of that relation. Within the simulation errors, P values obtained from the measured alpha and E T via this analytical expression agree with those determined from the simulations and E T values reckoned from the input alpha and kappa beta by this analytical expression agree with the corresponding simulated values. Although B is found to be insensitive to variation in alpha, it appears to decline slightly with increasing kappa beta. The original analytical expression is modified to take this apparent variation of B with kappa beta into account. By using this modified analytical relation to estimate P (from the measured alpha and E T ) or E T (from the input alpha and kappa beta), much closer agreement is obtained respectively with the values of P or E T obtained from the simulations. As specific examples, these methods are applied to determine P in 0 and 20 w/v % ethylene glycol, which has been shown to induce a structural transition in duplex DNA.


Assuntos
DNA Super-Helicoidal/química , Elasticidade/efeitos dos fármacos , Etilenoglicol/farmacologia , Torção Mecânica , Modelos Moleculares , Método de Monte Carlo , Conformação de Ácido Nucleico/efeitos dos fármacos , Reprodutibilidade dos Testes , Termodinâmica
12.
J Phys Chem B ; 112(30): 9219-36, 2008 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-18593148

RESUMO

The weakly bending rod (WBR) model of double-stranded DNA (dsDNA) is adapted to analyze the internal dynamics of dsDNA as observed in electron paramagnetic resonance (EPR) measurements of the spin-lattice relaxation rate, R(1e), for spin probes rigidly attached to nucleic acid-bases. The WBR theory developed in this work models dsDNA base-pairs as diffusing rigid cylindrical discs connected by bending and twisting springs whose elastic force constants are kappa and alpha, respectively. Angular correlation functions for both rotational displacement and velocity are developed in detail so as to compute values for R(1e) due to four relaxation mechanisms: the chemical shift anisotropy (CSA), the electron-nuclear dipolar (END), the spin rotation (SR), and the generalized spin diffusion (GSD) relaxation processes. Measured spin-lattice relaxation rates in dsDNA under 50 bp in length are much faster than those calculated for the same DNAs modeled as rigid rods. The simplest way to account for this difference is by allowing for internal flexibility in models of DNA. Because of this discrepancy, we derive expressions for the spectral densities due to CSA, END, and SR mechanisms directly from a weakly bending rod model for DNA. Special emphasis in this development is given to the SR mechanism because of the lack of such detail in previous treatments. The theory developed in this paper provides a framework for computing relaxation rates from the WBR model to compare with magnetic resonance relaxation data and to ascertain the twisting and bending force constants that characterize DNA.


Assuntos
DNA/química , Movimento , Marcadores de Spin , Espectroscopia de Ressonância de Spin Eletrônica , Modelos Moleculares , Conformação de Ácido Nucleico , Teoria Quântica
13.
Biophys J ; 94(10): 3798-809, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18234808

RESUMO

A simulated continuous wave electron paramagnetic resonance spectrum of a nitroxide spin label can be obtained from the Fourier transform of a free induction decay. It has been previously shown that the free induction decay can be calculated by solving the time-dependent stochastic Liouville equation for a set of Brownian trajectories defining the rotational dynamics of the label. In this work, a quaternion-based Monte Carlo algorithm has been developed to generate Brownian trajectories describing the global rotational diffusion of a spin-labeled protein. Also, molecular dynamics simulations of two spin-labeled mutants of T4 lysozyme, T4L F153R1, and T4L K65R1 have been used to generate trajectories describing the internal dynamics of the protein and the local dynamics of the spin-label side chain. Trajectories from the molecular dynamics simulations combined with trajectories describing the global rotational diffusion of the protein are used to account for all of the dynamics of a spin-labeled protein. Spectra calculated from these combined trajectories correspond well to the experimental spectra for the buried site T4L F153R1 and the helix surface site T4L K65R1. This work provides a framework to further explore the modeling of the dynamics of the spin-label side chain in the wide variety of labeling environments encountered in site-directed spin labeling studies.


Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Modelos Químicos , Modelos Moleculares , Muramidase/química , Muramidase/ultraestrutura , Doadores de Óxido Nítrico/química , Marcadores de Spin , Simulação por Computador , Difusão , Óxido Nítrico/química , Conformação Proteica
14.
Biopolymers ; 85(3): 222-32, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17111396

RESUMO

Upon increasing the concentration of ethylene glycol (EG) at 37 degrees C, the twist energy parameter, E(T), which governs the supercoiling free energy, was recently found to undergo a decreasing (or reverse) sigmoidal transition with a midpoint near 20 w/v % EG. In this study, the effects of adding 20 w/v % EG on the torsion elastic constant (alpha) of linear p30delta DNA and on the hydrodynamic radius (R(H)) of a synthetic 24 bp duplex DNA were examined at both 40 and 20 degrees C. The time-resolved fluorescence intensity and fluorescence polarization anisotropy (FPA) of intercalated ethidium were measured in order to assess the effects of 20 w/v % EG on: (1) alpha; (2) R(H); (3) the lifetimes of intercalated and non-intercalated dye; (4) the amplitude of dye wobble in its binding site; and (5) the binding constant for intercalation. The effects of 20 w/v % EG on the circular dichroism (CD) spectrum of the DNA and on the emission spectrum of the free dye were also measured. At 40 degrees C, addition of 20 w/v % EG caused a substantial (1.27- to 1.35-fold) increase in alpha, a significant change in the CD spectrum, and a very small, marginally significant increase in R(H), but little or no change in the amplitude of dye wobble in its binding site or the lifetime of intercalated dye. Together with previously reported measurements of E(T), these results imply that the bending elastic constant of DNA is significantly decreased by 20 w/v % EG at 40 degrees C. At 20 degrees C, addition of 20 w/v % EG caused a marginally significant decrease in alpha and very little change in any other measured properties. Also at 20 degrees C, addition of 30 w/v % betaine caused a marginally significant increase in alpha and significant but modest change in the CD spectrum, but very little change in any other properties.


Assuntos
DNA/química , Etilenoglicol/química , Plasmídeos/química , Água/química , Dicroísmo Circular , Elasticidade , Etídio/química , Viscosidade
15.
Biophys J ; 89(4): 2258-76, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16055532

RESUMO

A simple and complete derivation of the relation between concentration-based preferential interaction coefficients and integrals over the relevant pair correlation functions is presented for the first time. Certain omissions from the original treatment of pair correlation functions in multicomponent thermodynamics are also addressed. Connections between these concentration-based quantities and the more common molality-based preferential interaction coefficients are also derived. The pair correlation functions and preferential interaction coefficients of both solvent (water) and cosolvent (osmolyte) in the neighborhood of a macromolecule contain contributions from short-range repulsions and generic long-range attractions originating from the macromolecule, as well as from osmolyte-solvent exchange reactions beyond the macromolecular surface. These contributions are evaluated via a heuristic analysis that leads to simple insightful expressions for the preferential interaction coefficients in terms of the volumes excluded to the centers of the water and osmolyte molecules and a sum over the contributions of exchanging sites in the surrounding solution. The preferential interaction coefficients are predicted to exhibit the experimentally observed dependence on osmolyte concentration. Molality-based preferential interaction coefficients that were reported for seven different osmolytes interacting with bovine serum albumin are analyzed using the this formulation together with geometrical parameters reckoned from the crystal structure of human serum albumin. In all cases, the excluded volume contribution, which is the volume excluded to osmolyte centers minus that excluded to water centers in units of V1, exceeds in magnitude the contribution of the exchange reactions. Under the assumption that the exchange contribution is dominated by sites in the first surface-contiguous layer, the ratio of the average exchange constant to its neutral random value is determined for each osmolyte. These ratios all lie in the range 1.0 +/- 0.15, which indicates rather slight deviations from random occupation near the macromolecular surface. Finally, a mechanism is proposed whereby the chemical identity of an osmolyte might be concealed from partially ordered multilayers of water in clefts, grooves, and pits, and its consequences are noted.


Assuntos
Biopolímeros/química , Modelos Químicos , Soroalbumina Bovina/química , Água/química , Algoritmos , Sítios de Ligação , Simulação por Computador , Pressão Osmótica , Ligação Proteica , Termodinâmica
16.
Biopolymers ; 75(4): 291-313, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15386272

RESUMO

Both theory and experiments are employed to investigate the effects of small neutral osmolytes on the average intrinsic twist (l0), the torsion and bending elastic constants, and the twist energy parameter (ET) that governs the supercoiling free energy. The experimental data for ethylene glycol and acetamide at 37 degrees C suggest, and are interpreted in terms of, a model wherein the DNA exhibits an equilibrium between two distinct conformational states that possess different numbers of bound water molecules and exhibit different intrinsic twists and torsion and bending elastic constants. Expressions are derived to relate the effective ET and l0 to the equilibrium constant, water activity (aw), and number (n) of bound water molecules released per cooperative domain undergoing the two-state transition. The variations of l0 and ET with -ln(aw) are similar for acetamide and ethylene glycol at 37 degrees C. Fitting the theory to those data yields the range n = 103-125 for ethylene glycol and n = 71-113 for acetamide, depending on the assumed value of ET for the dehydrated state. The cooperative domain size of the two-state transition is estimated to exceed about 25-30 base pairs (bp). Between 0 and 19.4 w/v % ethylene glycol, the torsion elastic constant, measured by time-resolved fluorescence polarization anisotropy (FPA), increases by 1.37-fold, whereas the measured ET decreases by 1.15-fold over that same range. The implied decrease in bending rigidity over that range is by a factor of about 0.7. The variations of l0 and ET with increasing -ln(aw) due to added ethylene glycol at 37 degrees C are far smaller than the corresponding variations observed previously at 14 and 15 degrees C. However, at 21 degrees C, upon adding either ethylene glycol or acetamide, l0 and ET initially decline steeply with increasing -ln(aw), with slopes possibly comparable to those seen at 14 and 15 degrees C, but then flatten out and follow curves similar to those at 37 degrees C. Possible origins of such mixed behavior are discussed. The effects of betaine at both 37 and 21 degrees C differ qualitatively and quantitatively in various respects from those of ethylene glycol and acetamide. Upon adding sucrose, l0 initially jumps to higher plateaus at both 37 and 21 degrees C, but its effects on ET cannot be reliably assessed, due to the limited range of -ln(aw).


Assuntos
DNA Super-Helicoidal/química , Acetamidas , Etilenoglicol , Polarização de Fluorescência , Conformação de Ácido Nucleico , Concentração Osmolar , Termodinâmica , Água
17.
Biophys J ; 86(5): 3079-96, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15111422

RESUMO

Mesoscopic models of unmelted and locally melted supercoiled DNAs in 20 mM ionic strength are simulated over a range of linking difference from deltal = 0 to -26 turns, or superhelix density from sigma = 0 to -0.062. A domain containing m = 0, 28, or 56 melted basepairs (out of 4349 total) is modeled simply by a region of suitable length with substantially reduced torsion and bending elastic constants. Average structural properties are calculated from the saved configurations, and a reversible work protocol is used to calculate the supercoiling free energy, The cross-writhe between duplex and melted regions (defined herein) is found to be negligibly small. The total writhe, radius of gyration, and ordered elements of the diagonalized inertial tensor are found to be nearly universal functions of the residual linking difference (deltal(r)) associated with the duplex region, independent of m. However, deformability of the tertiary structure, as manifested by the variance of those same properties, is not a universal function of deltal(r)), but depends upon m.delta (SC) varies with deltal(r)) more strongly than deltal(r)) (2)due to the low ionic strength. The twist energy parameter, E (T) obtained from the simulated delta G(SC), deltal(r)), and net twisting strain of the melted region T (D), is found to be independent of m, hence also of the torsion and bending elastic constants of the melted region. However, E(T) increases linearly with -deltalr), which leads to 1). a small overestimation of E (T) for any given deltal(r)) when E(T) is determined from the observed deltal and deltal (r) by the protocol of Bauer and Benham; and 2). a significant enhancement of the apparent slope, -dE(T)/d(T), obtained via the protocol of Bauer and Benham, relative to the actual slope at fixed delta l(r). After taking these two effects into account, the theoretical and experimental values E(T) and -dE(T)/d(T) values agree rather well. For the larger deltal the melted regions are found preferentially in the linker domains between interwound arms, rather than in the apical regions at the ends of interwound arms.


Assuntos
Biofísica/métodos , DNA Super-Helicoidal/química , Conformação de Ácido Nucleico , Simulação por Computador , DNA/química , Íons , Modelos Moleculares , Modelos Estatísticos , Método de Monte Carlo , Distribuição Normal , Temperatura , Termodinâmica
18.
Acta Haematol ; 110(4): 179-83, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14663161

RESUMO

BACKGROUND: Methods to simplify the stem cell transplantation procedures are needed mainly in developing countries. We have previously shown that unprocessed leukapheresis material is useful to restore hematopoiesis after high-dose chemotherapy. METHODS: Over a 10-year period in a private practice setting, we prospectively performed autotransplants using noncryopreserved and unmanipulated peripheral blood stem cells mobilized from the bone marrow to the peripheral blood by means of filgrastim and using a single-day conditioning regimen with high dose (200 mg/m2) melphalan. RESULTS: Forty-six individuals were given 50 autografts. The median age of the patients was 33 years (range 8-69). Twenty-two patients with acute leukemia (13 with myeloblastic and 9 with lymphoblastic leukemia), 4 with chronic myelogenous leukemia, 6 with multiple myeloma, 7 with Hodgkin's disease, 3 with non-Hodgkin's lymphoma and 4 with metastatic breast carcinoma were included. The median time to achieve >0.5 x 10(9)/l granulocytes was 14 days (range 0-86), whereas the median time to achieve >20 x 10(9)/l platelets was 25 days (range 0-102). The 3,300-day posttransplant survival was 63%, the median posttransplant overall survival was over 3,300 days, the 3,300-day disease-free survival was 50% and the transplant-related mortality was 2%. The procedure was performed entirely on an outpatient basis in the case of 48 autografts (96%). The approximate cost of each graft was 7,500 USD. CONCLUSION: This simplified method to autograft patients, avoiding in-hospital stays, purging procedures and cryopreservation of the cells, is feasible and results in a substantial decrease in the cost of the autologous hematopoietic stem cell transplantation methods.


Assuntos
Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Criança , Criopreservação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Hematology ; 8(3): 151-4, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12745648

RESUMO

We report our experience of allogeneic peripheral blood stem cell transplantation using non-myeloablative conditioning regimens delivered and supported on an outpatient basis. A group of 44 patients underwent 47 allograft procedures using peripheral blood stem cells. Approximately one third of the individuals did not require red blood cells transfusions: the median of transfused red blood cells units was 1 (range 0-10). In addition one out of three did not require platelet transfusions either, the median of platelet transfusions being 1 (range 0-6). In fourteen allografts (30%) neither red blood cells nor platelet transfusions were used. An inverse correlation was found between the number of CD34 cells infused and the PRBC and PLT transfusion requirements, those patients receiving high numbers of CD34 cells needing fewer transfusions of both PRBC and platelets. The possibility of conducting allografts without transfusion of blood products in some patients may result in a decrease in both cost and the risks stemming from exposure to human blood derivatives.


Assuntos
Transfusão de Eritrócitos/estatística & dados numéricos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Transfusão de Plaquetas/estatística & dados numéricos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Bussulfano , Criança , Pré-Escolar , Ciclofosfamida , Ciclosporina , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas , Humanos , Masculino , Metotrexato , Pessoa de Meia-Idade , Neoplasias/terapia , Transplante de Células-Tronco de Sangue Periférico/estatística & dados numéricos , Estudos Prospectivos , Proteínas Recombinantes , Transplante Homólogo
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