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1.
ACS Omega ; 4(3): 5640-5649, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459718

RESUMO

In this work, we describe the preparation and characterization of highly magnetizable chloromethylated polystyrene-based nanocomposite beads. For synthesis optimization, acid-resistant core-shelled maghemite (γ-Fe2O3) nanoparticles are coated with sodium oleate and directly incorporated into the organic medium during a suspension polymerization process. A crosslinking agent, ethylene glycol dimethacrylate, is used for copolymerization with 4-vinylbenzyl chloride to increase the resistance of the microbeads against leaching. X-ray diffraction, inductively coupled plasma atomic emission spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, and optical microscopy are used for bead characterization. The beads form a magnetic composite consisting of ∼500 nm-sized crosslinked polymeric microspheres, embedding ∼8 nm γ-Fe2O3 nanoparticles. This nanocomposite shows large room temperature magnetization (∼24 emu/g) due to the high content of maghemite (∼45 wt %) and resistance against leaching even in acidic media. Moreover, the presence of superficial chloromethyl groups is probed by Fourier transform infrared and X-ray photoelectron spectroscopy. The nanocomposite beads displaying chloromethyl groups can be used to selectively remove aminated compounds that are adsorbed on the beads, as is shown here for the molecular separation of 4-aminobenzoic acid from a mixture with benzoic acid. The high magnetization of the composite beads makes them suitable for in situ molecular separations in environmental and biological applications.

2.
J Hazard Mater ; 264: 153-60, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-24295766

RESUMO

Maghemite nanoparticles (MNPs) were functionalized with glycine, by a cost-effective and environmentally friendly procedure, as an alternative route to typical amine-functionalized polymeric coatings, for highly efficient removal of copper ions from water. MNPs were synthesized by co-precipitation method and adsorption of glycine was investigated as a function of ligand concentration and pH. The efficiency of these functionalized nanoparticles for removal of Cu(2+) from water has been explored and showed that adsorption is highly dependent of pH and that it occurs either by forming chelate complexes and/or by electrostatic interaction. The adsorption process, which reaches equilibrium in few minutes and fits a pseudo second-order model, follows the Langmuir adsorption model with a very high maximum adsorption capacity for Cu(2+) of 625mg/g. Furthermore, these nanoadsorbents can be used as highly efficient separable and reusable materials for removal of toxic metal ions.


Assuntos
Cobre/isolamento & purificação , Compostos Férricos/química , Glicina/química , Nanopartículas Metálicas/química , Poluentes Químicos da Água/isolamento & purificação , Águas Residuárias/química
3.
ACS Appl Mater Interfaces ; 4(10): 5458-65, 2012 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-22966984

RESUMO

̀This paper reports on the advancement of magnetic ionic liquids (MILs) as stable dispersions of surface-modified γ-Fe(2)O(3), Fe(3)O(4), and CoFe(2)O(4) magnetic nanoparticles (MNPs) in a hydrophobic ionic liquid, 1-n-butyl 3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf(2)). The MNPs were obtained via coprecipitation and were characterized using powder X-ray diffraction, transmission electron microscopy, Raman spectroscopy and Fourier transform near-infrared (FT-NIR) spectroscopy, and magnetic measurements. The surface-modified MNPs (SM-MNPs) were obtained via the silanization of the MNPs with the aid of 1-butyl-3-[3-(trimethoxysilyl)propyl]imidazolium chloride (BMSPI.Cl). The SM-MNPs were characterized by Raman spectroscopy and Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy and by magnetic measurements. The FTIR-ATR spectra of the SM-MNPs exhibited characteristic absorptions of the imidazolium and those of the Fe-O-Si-C moieties, confirming the presence of BMSPI.Cl on the MNP surface. Thermogravimetric analysis (TGA) showed that the SM-MNPs were modified by at least one BMSPI.Cl monolayer. The MILs were characterized using Raman spectroscopy, differential scanning calorimetry (DSC), and magnetic measurements. The Raman and DSC results indicated an interaction between the SM-MNPs and the IL. This interaction promotes the formation of a supramolecular structure close to the MNP surface that mimics the IL structure and is responsible for the stability of the MIL. Magnetic measurements of the MILs indicated no hysteresis. Superparamagnetic behavior and a saturation magnetization of ~22 emu/g could be inferred from the magnetic measurements of a sample containing 50% w/w γ-Fe(2)O(3) SM-MNP/BMI.NTf(2).


Assuntos
Imidazóis/química , Imidas/química , Líquidos Iônicos/química , Nanopartículas de Magnetita/química , Compostos Férricos/química , Óxido Ferroso-Férrico/química , Interações Hidrofóbicas e Hidrofílicas , Termogravimetria
4.
J Natl Cancer Inst ; 93(21): 1624-32, 2001 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-11698566

RESUMO

BACKGROUND: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes. Women with atypical breast ductal epithelial cells have an increased relative risk of breast cancer. In this study, ductal lavage, a new procedure for collecting ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. METHODS: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by lavage of fluid-yielding ducts. All statistical tests were two-sided. RESULTS: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7% or more. Nipple aspirate fluid (NAF) samples were evaluated cytologically for 417 women, and ductal lavage samples were evaluated for 383 women. Adequate samples for diagnosis were collected from 111 (27%) and 299 (78%) women, respectively. A median of 13,500 epithelial cells per duct (range, 43-492,000 cells) was collected by ductal lavage compared with a median of 120 epithelial cells per breast (range, 10-74,300) collected by nipple aspiration. For ductal lavage, 92 (24%) subjects had abnormal cells that were mildly (17%) or markedly (6%) atypical or malignant (<1%). For NAF, corresponding percentages were 6%, 3%, and fewer than 1%. Ductal lavage detected abnormal intraductal breast cells 3.2 times more often than nipple aspiration (79 versus 25 breasts; McNemar's test, P<.001). No serious procedure-related adverse events were reported. CONCLUSIONS: Large numbers of ductal cells can be collected by ductal lavage to detect atypical cellular changes within the breast. Ductal lavage is a safe and well-tolerated procedure and is a more sensitive method of detecting cellular atypia than nipple aspiration.


Assuntos
Neoplasias da Mama/diagnóstico , Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Neoplasias da Mama/patologia , Citodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Irrigação Terapêutica
5.
J Virol ; 75(22): 10563-72, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11602698

RESUMO

Different subgroups of feline leukemia virus (FeLV) use different host cell receptors for entry. Subgroup A FeLV (FeLV-A) is the virus that is transmitted from cat to cat, suggesting that cells expressing the FeLV-A receptor are important targets at the earliest stages of infection. FeLV-B evolves from FeLV-A in the infected cat through acquisition of cellular sequences that are related to the FeLV envelope gene. FeLV-Bs have been shown to infect cells using the Pit1 receptor, and some variants can infect cells at a lower efficiency using Pit2. Because these observations were made using receptor proteins of human or rodent origin, the role that Pit1 and Pit2 may play in FeLV-B replication in the cat is unclear. In this study, the feline Pit receptors were cloned and tested for their ability to act as receptors for different FeLV-Bs. Some FeLV-Bs infected cells expressing feline Pit2 and feline Pit1 with equal high efficiency. Variable region A (VRA) in the putative receptor-binding domain (RBD) was a critical determinant for both feline Pit1 and feline Pit2 binding, although other domains in the RBD appear to influence how efficiently the FeLV-B surface unit can bind to feline Pit2 and promote entry via this receptor. An arginine residue at position 73 in VRA was found to be important for envelope binding to feline Pit2 but not feline Pit1. Interestingly, this arginine is not found in endogenous FeLV sequences or in recombinant viruses recovered from feline cells infected with FeLV-A. Thus, while FeLV-Bs that are able to use feline Pit2 can evolve by recombination with endogenous sequences, a subsequent point mutation during reverse transcription may be needed to generate a virus that can efficiently enter the cells using the feline Pit2 as its receptor. These studies suggest that cells expressing the feline Pit2 protein are likely to be targets for FeLV-B infection in the cat.


Assuntos
Vírus da Leucemia Felina/classificação , Receptores Virais/fisiologia , Sequência de Aminoácidos , Animais , Evolução Biológica , Gatos , Linhagem Celular , Humanos , Dados de Sequência Molecular , Receptores Virais/química
6.
J Virol ; 75(19): 8888-98, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11533152

RESUMO

Cytopathic, T-cell-tropic feline leukemia viruses (FeLV-T) evolve from FeLV-A in infected animals and demonstrate host cell specificities that are distinct from those of their parent viruses. We recently identified two cellular proteins, FeLIX and Pit1, required for productive infection by these immunodeficiency-inducing FeLV-T variants (M. M. Anderson, A. S. Lauring, C. C. Burns, and J. Overbaugh, Science 287:1828-1830, 2000). FeLV-T is the first example of a naturally occurring type C retrovirus that requires two proteins to gain entry into target cells. FeLIX is an endogenous protein that is highly related to the N-terminal portion of the FeLV envelope protein, which includes the receptor-binding domain. Pit1 is a multiple-transmembrane phosphate transport protein that also functions as a receptor for FeLV-B. The FeLV-B envelope gene is derived by recombination with endogenous FeLV-like sequences, and its product can functionally substitute for FeLIX in facilitating entry through the Pit1 receptor. In the present study, we tested other retrovirus envelope surface units (SUs) with their cognate receptors to determine whether they also could mediate infection by FeLV-T. Cells were engineered to coexpress the transmembrane form of the envelope proteins and their cognate receptors, or SU protein was added as a soluble protein to cells expressing the receptor. Of the FeLV, murine leukemia virus, and gibbon ape leukemia virus envelopes tested, we found that only those with receptor-binding domains derived from endogenous FeLV could render cells permissive for FeLV-T. We also found that there is a strong preference for Pit1 as the transmembrane receptor. Specifically, FeLV-B SUs could efficiently mediate infection of cells expressing the Pit1 receptor but could only inefficiently mediate infection of cells expressing the Pit2 receptor, even though these SUs are able to bind to Pit2. Expression analysis of feline Pit1 and FeLIX suggests that FeLIX is likely the primary determinant of FeLV-T tropism. These results are discussed in terms of current models for retrovirus entry and the interrelationship among FeLV variants that evolve in vivo.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Vírus da Leucemia Felina/fisiologia , Proteínas de Membrana/fisiologia , Receptores Virais/fisiologia , Infecções por Retroviridae/virologia , Fatores de Transcrição/fisiologia , Infecções Tumorais por Vírus/virologia , Animais , Linhagem Celular , Humanos , Especificidade de Órgãos , Fator de Transcrição Pit-1 , Replicação Viral
7.
J Virol ; 75(15): 6841-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11435563

RESUMO

The retroviral vector systems that are in common use for gene therapy are designed to infect cells expressing either of two widely expressed phosphate transporter proteins, Pit1 or Pit2. Subgroup B feline leukemia viruses (FeLV-Bs) use the gibbon ape leukemia virus receptor, Pit1, as a receptor for entry. Our previous studies showed that some chimeric envelope proteins encoding portions of FeLV-B could also enter cells by using a related receptor protein, Pit2, which serves as the amphotropic murine leukemia virus receptor (S. Boomer, M. Eiden, C. C. Burns, and J. Overbaugh, J. Virol. 71:8116--8123, 1997). Here we show that an arginine at position 73 within variable region A (VRA) of the FeLV-B envelope surface unit (SU) is necessary for viral entry into cells via the human Pit2 receptor. However, C-terminal SU sequences have a dominant effect in determining human Pit2 entry, even though this portion of the protein is outside known receptor binding domains. This suggests that a combination of specific VRA sequences and C-terminal sequences may influence interactions between FeLV-B SU and the human Pit2 receptor. Binding studies suggest that the C-terminal sequences may affect a postbinding step in viral entry via the Pit2 receptor, although in all cases, binding of FeLV-B SU to human Pit2 was weak. In contrast, neither the arginine 73 nor specific C-terminal sequences are required for efficient binding or infection with Pit1. Taken together, these data suggest that different residues in SU may interact with these two receptors. The specific FeLV-Bs described here, which can enter cells using either human Pit receptor, may be useful as envelope pseudotypes for viruses used in gene therapy.


Assuntos
Proteínas de Transporte/metabolismo , Vírus da Leucemia Felina/metabolismo , Receptores Virais/metabolismo , Simportadores , Proteínas do Envelope Viral/metabolismo , Animais , Sítios de Ligação , Proteínas de Transporte/genética , Gatos , Linhagem Celular , Linhagem Celular Transformada , Técnicas de Transferência de Genes , Humanos , Vírus da Leucemia Felina/genética , Camundongos , Receptores Virais/genética , Proteínas Cotransportadoras de Sódio-Fosfato , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III , Proteínas do Envelope Viral/genética
8.
J Clin Invest ; 107(4): 419-30, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11181641

RESUMO

Myeloperoxidase (MPO), a heme enzyme secreted by activated phagocytes, generates an array of oxidants proposed to play critical roles in host defense and local tissue damage. Both MPO and its reaction products are present in human atherosclerotic plaque, and it has been proposed that MPO oxidatively modifies targets in the artery wall. We have now generated MPO-deficient mice, and show here that neutrophils from homozygous mutants lack peroxidase and chlorination activity in vitro and fail to generate chlorotyrosine or to kill Candida albicans in vivo. To examine the potential role of MPO in atherosclerosis, we subjected LDL receptor-deficient mice to lethal irradiation, repopulated their marrow with MPO-deficient or wild-type cells, and provided them a high-fat, high-cholesterol diet for 14 weeks. White cell counts and plasma lipoprotein profiles were similar between the two groups at sacrifice. Cross-sectional analysis of the aorta indicated that lesions in MPO-deficient mice were about 50% larger than controls. Similar results were obtained in a genetic cross with LDL receptor-deficient mice. In contrast to advanced human atherosclerotic lesions, the chlorotyrosine content of aortic lesions from wild-type as well as MPO-deficient mice was essentially undetectable. These data suggest an unexpected, protective role for MPO-generated reactive intermediates in murine atherosclerosis. They also identify an important distinction between murine and human atherosclerosis with regard to the potential involvement of MPO in protein oxidation.


Assuntos
Arteriosclerose/etiologia , Peroxidase/fisiologia , Tirosina/análogos & derivados , Animais , Candida albicans/imunologia , Humanos , Ácido Hipocloroso/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/enzimologia , Oxirredução , Peroxidase/deficiência , Peroxidase/genética , Fagócitos/metabolismo , Tirosina/análise
9.
Science ; 287(5459): 1828-30, 2000 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-10710311

RESUMO

Retroviral infection involves continued genetic variation, leading to phenotypic and immunological selection for more fit virus variants in the host. For retroviruses that cause immunodeficiency, pathogenesis is linked to the emergence of T cell-tropic, cytopathic viruses. Here we show that an immunodeficiency-inducing, T cell-tropic feline leukemia virus (FeLV) has evolved such that it cannot infect cells unless both a classic multiple membrane-spanning receptor molecule (Pit1) and a second coreceptor or entry factor are present. This second receptor component, which we call FeLIX, was identified as an endogenously expressed protein that is similar to a portion of the FeLV envelope protein. This cellular protein can function either as a transmembrane protein or as a soluble component to facilitate infection.


Assuntos
Vírus da Leucemia Felina/fisiologia , Proteínas de Membrana/fisiologia , Receptores Virais/fisiologia , Animais , Gatos , Linhagem Celular , Clonagem Molecular , Cães , Evolução Molecular , Vírus da Leucemia Felina/genética , Proteínas de Membrana/química , Proteínas de Membrana/genética , Dados de Sequência Molecular , Muridae , Sinais Direcionadores de Proteínas/química , Sinais Direcionadores de Proteínas/genética , Sinais Direcionadores de Proteínas/fisiologia , Receptores Virais/química , Receptores Virais/genética , Linfócitos T/metabolismo , Linfócitos T/virologia , Células Tumorais Cultivadas
10.
Blood ; 95(3): 1093-9, 2000 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-10648427

RESUMO

Feline leukemia virus-C (FeLV-C) causes red cell aplasia in cats, likely through its interaction with its cell surface receptor. We identified this receptor by the functional screening of a library of complementary DNAs (cDNA) from feline T cells. The library, which was cloned into a retroviral vector, was introduced into FeLV-C-resistant murine (NIH 3T3) cells. The gene conferring susceptibility to FeLV-C was isolated and reintroduced into the same cell type, as well as into FeLV-C-resistant rat (NRK 52E) cells, to verify its role in viral infection. The receptor cDNA is predicted to encode a protein of 560 amino acids with 12 membrane-spanning domains, termed FLVCR. FLVCR has significant amino acid sequence homology with members of the major facilitator superfamily and especially D-glucarate transporters described in bacteria and in C. elegans. As FeLV-C impairs the in vivo differentiation of burst-forming unit-erythroid to colony-forming unit-erythroid, we hypothesize that this transporter system could have an essential role in early erythropoiesis. In further studies, a 6-kb fragment of the human FLVCR gene was amplified by polymerase chain reaction from genomic DNA, using homologous cDNA sequences identified in the human Expressed Sequence Tags database. By radiation hybrid mapping, the human gene was localized to a 0.5-centiMorgan region on the long arm of chromosome 1 at q31.3.


Assuntos
Gatos/genética , Vírus da Leucemia Felina/patogenicidade , Receptores Virais/genética , Aplasia Pura de Série Vermelha/etiologia , Infecções por Retroviridae/complicações , Células 3T3 , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Caenorhabditis elegans/genética , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 1/genética , Clonagem Molecular , DNA Complementar/genética , Células Precursoras Eritroides/patologia , Eritropoese/genética , Escherichia coli/genética , Etiquetas de Sequências Expressas , Predisposição Genética para Doença , Proteínas de Helminto/química , Proteínas de Helminto/genética , Humanos , Células Híbridas , Vírus da Leucemia Felina/metabolismo , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Ratos , Receptores Virais/biossíntese , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
11.
J Nat Prod ; 63(12): 1638-40, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11141105

RESUMO

Twenty-one alkaloids have been assessed for activities against Plasmodium falciparum (multidrug- resistant strain K1) in vitro; 18 of these are reported for the first time. Two protoberberine alkaloids, dehydrodiscretine and berberine, were found to have antiplasmodial IC(50) values less than 1 M, while seven alkaloids-allocrytopine, columbamine, dehydroocoteine, jatrorrhizine, norcorydine, thalifendine, and ushinsunine-had values between 1 and 10 M. These results are discussed in the context of structure-activity relationships. Compounds were also assessed for antiamoebic and cytotoxic activities, but none was significantly active except for berberine, which was moderately cytotoxic.


Assuntos
Alcaloides/farmacologia , Amebicidas/farmacologia , Antimaláricos/farmacologia , Isoquinolinas/farmacologia , Alcaloides/química , Amebicidas/química , Animais , Antimaláricos/química , Entamoeba histolytica/efeitos dos fármacos , Isoquinolinas/química , Plasmodium falciparum/efeitos dos fármacos , Relação Estrutura-Atividade
12.
J Clin Invest ; 104(1): 103-13, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10393704

RESUMO

Reactive aldehydes derived from reducing sugars and peroxidation of lipids covalently modify proteins and may contribute to oxidative tissue damage. We recently described another mechanism for generating reactive aldehydes from free alpha-amino acids. The pathway begins with myeloperoxidase, a heme enzyme secreted by activated neutrophils. Conversion of alpha-amino acids to aldehydes requires hypochlorous acid (HOCl), formed from H2O2 and chloride by myeloperoxidase. When L-serine is the substrate, HOCl generates high yields of glycolaldehyde. We now demonstrate that a model protein, ribonuclease A (RNase A), exposed to free L-serine and HOCl exhibits the biochemical hallmarks of advanced glycation end (AGE) products -- browning, increased fluorescence, and cross-linking. Furthermore, Nepsilon-(carboxymethyl)lysine (CML), a chemically well-characterized AGE product, was generated on RNase A when it was exposed to reagent HOCl-serine, the myeloperoxidase-H2O2-chloride system plus L-serine, or activated human neutrophils plus L-serine. CML production by neutrophils was inhibited by the H2O2 scavenger catalase and the heme poison azide, implicating myeloperoxidase in the cell-mediated reaction. CML was also generated on RNase A by a myeloperoxidase-dependent pathway when neutrophils were activated in a mixture of amino acids. Under these conditions, we observed both L-serine-dependent and L-serine-independent pathways of CML formation. The in vivo production of glycolaldehyde and other reactive aldehydes by myeloperoxidase may thus play an important pathogenic role by generating AGE products and damaging tissues at sites of inflammation.


Assuntos
Inflamação/enzimologia , Lisina/análogos & derivados , Peroxidase/metabolismo , Processamento de Proteína Pós-Traducional , Aldeídos/metabolismo , Catalase/farmacologia , Cátions , Células Cultivadas , Quelantes/farmacologia , Glicosilação , Humanos , Peróxido de Hidrogênio/metabolismo , Ácido Hipocloroso/metabolismo , Ácido Hipocloroso/farmacologia , Inflamação/patologia , Lisina/biossíntese , Reação de Maillard , Neutrófilos/enzimologia , Oxirredução , Ribonuclease Pancreático/efeitos dos fármacos , Serina/farmacologia , Azida Sódica/farmacologia
13.
Am J Clin Pathol ; 111(4): 495-500, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10191769

RESUMO

Six patients with mantle cell lymphoma, blastoid variant, involving the blood are described. The circulating blast-like cells suggested the possibility of acute leukemias, chronic lymphoproliferative disorders or peripheralized lymphomas. The WBC counts ranged from 3,700 to 249,000/microL (3.7-249.0 x 10(9)/L) and the absolute lymphocyte counts from 1,000 to more than 200,000/microL (1.0 to > 200.0 x 10(9)/L). The peripheral blood smears showed a spectrum of cells, from small mature lymphocytes with irregular nuclei to medium-sized lymphocytes with blast-like chromatin. However, the morphologic features in a lymph node biopsy specimen and the immunophenotype confirmed a diagnosis of mantle cell lymphoma, blastoid variant. By flow cytometry the lymphoma cells expressed B-cell-associated antigens (CD19, CD20 and CD22), coexpressed CD5, lacked CD23, and expressed moderate intensity monoclonal surface immunoglobulin and CD20. Cytogenetic analysis showed the characteristic t(11;14) in 2 of 4 analyzed specimens. Mantle cell lymphoma, blastoid variant, is part of the differential diagnosis for blast-like cells.


Assuntos
Linfoma não Hodgkin/patologia , Idoso , Anticorpos Monoclonais/análise , Antígenos de Diferenciação de Linfócitos B/análise , Células da Medula Óssea/patologia , Núcleo Celular/patologia , Cromatina/patologia , Feminino , Citometria de Fluxo , Hepatomegalia , Humanos , Imunofenotipagem , Contagem de Leucócitos , Linfonodos/patologia , Contagem de Linfócitos , Linfócitos/patologia , Linfócitos/ultraestrutura , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Esplenomegalia
15.
J Biol Chem ; 273(9): 4997-5005, 1998 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-9478947

RESUMO

We have recently demonstrated that neutrophils oxidize nearly all of the amino acids commonly found in plasma to a corresponding family of aldehydes in high yield. The reaction is mediated by hypochlorous acid (HOCl), the major oxidant generated by the myeloperoxidase-H2O2-Cl- system of phagocytes. We now present evidence for the underlying mechanism of this reaction, including the structural requirements and reaction intermediates formed. Utilizing mass spectrometry and isotopically labeled amino acids, we rule out hydrogen atom abstraction from the alpha-carbon as the initial event in aldehyde formation during amino acid oxidation, a pathway known to occur with ionizing radiation. Aldehyde generation from amino acids required the presence of an alpha-amino moiety; beta- and epsilon-amino acids did not form aldehydes upon oxidation by either the myeloperoxidase system or HOCl, generating stable monochloramines instead. UV difference spectroscopy, high pressure liquid chromatography, and multinuclear (1H,15N) NMR spectroscopy established that the conversion of alpha-amino acids into aldehydes begins with generation of an unstable alpha-monochloramine, which subsequently decomposes to yield an aldehyde. Precursor product relationships between alpha-amino acid and alpha-monochloramine, and alpha-monochloramine and aldehyde were confirmed by high pressure liquid chromatography purification of the reaction intermediate and subsequent 1H and 15N NMR spectroscopy. Collectively, these results detail the chemical mechanism and reaction intermediates generated during conversion of amino acids into aldehydes by myeloperoxidase-generated HOCl.


Assuntos
Aldeídos/metabolismo , Aminoácidos/metabolismo , Neutrófilos/metabolismo , Peroxidase/metabolismo , Cloraminas/metabolismo , Cloretos/metabolismo , Humanos , Ácido Hipocloroso/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Espectrometria de Massas , Modelos Químicos , Isótopos de Nitrogênio , Ressonância Magnética Nuclear Biomolecular , Oxirredução , Fenilalanina/metabolismo , Tirosina/metabolismo
16.
Ugeskr Laeger ; 159(37): 5514-8, 1997 Sep 08.
Artigo em Dinamarquês | MEDLINE | ID: mdl-9312920

RESUMO

The aim of our study was to evaluate the effect of metoprolol on the occurrence of myocardial ischaemia during endoscopic cholangiopancreatography. Thirty-eight (2 x 19) patients scheduled for endoscopic cholangiopancreatography received either metoprolol 100 mg or placebo two hours before endoscopy. During endoscopy, arterial oxygen saturation was measured by continuous pulse oximetry, and the electrocardiogram was monitored continuously with a Holter tape recorder. Myocardial ischaemia was defined as an ST segment deviation > 1 mV from baseline. Heart rate during endoscopy was significantly lower in the metoprolol group compared with the placebo group (p = 0.0002). Twenty-one patients (16 placebo versus five metoprolol, p = 0.0008) developed tachycardia (heart rate > 100/min) during the procedure. A total of eleven patients (ten placebo versus one metoprolol, p = 0.003) developed myocardial ischaemia during the procedure, and myocardial ischaemia was always related to increases in heart rate. In conclusion, metoprolol prevented myocardial ischaemia during endoscopic cholangiopancreatography, probably through a heart rate lowering effect. Thus, tachycardia seems to be a key pathogenic factor in the development of myocardial ischaemia during endoscopy.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antiarrítmicos/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Metoprolol/administração & dosagem , Isquemia Miocárdica/prevenção & controle , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia
17.
Nurse Pract ; 22(3): 179-80, 183-6, 189 passim, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9078522

RESUMO

This article describes the increasing use of the telephone as a means for seeking medical care. The literature is reviewed concerning the problems and pitfalls of telephone advice. The legal/ethical implications of health care providers giving telephone advice are discussed. Recommendations for the assessment of need, planning, implementation, and organization of a consistent telephone advice program are stressed. The development of a quality assurance program to maintain the quality of the advice program is presented. Suggestions for training of personnel and the importance of documentation of calls are included.


Assuntos
Aconselhamento/organização & administração , Linhas Diretas/organização & administração , Profissionais de Enfermagem , Triagem/organização & administração , Protocolos Clínicos , Humanos , Avaliação em Enfermagem , Planejamento de Assistência ao Paciente , Garantia da Qualidade dos Cuidados de Saúde , Encaminhamento e Consulta
18.
J Clin Invest ; 99(3): 424-32, 1997 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-9022075

RESUMO

Reactive aldehydes derived from reducing sugars and lipid peroxidation play a critical role in the formation of advanced glycation end (AGE) products and oxidative tissue damage. We have recently proposed another mechanism for aldehyde generation at sites of inflammation that involves myeloperoxidase, a heme enzyme secreted by activated phagocytes. We now demonstrate that human neutrophils employ the myeloperoxidase-H202-chloride system to produce alpha-hydroxy and alpha,beta-unsaturated aldehydes from hydroxy-amino acids in high yield. Identities of the aldehydes were established using mass spectrometry and high performance liquid chromatography. Activated neutrophils converted L-serine to glycolaldehyde, an alpha-hydroxyaldehyde which mediates protein cross-linking and formation of Nepsilon-(carboxymethyl)lysine, an AGE product. L-Threonine was similarly oxidized to 2-hydroxypropanal and its dehydration product, acrolein, an extremely reactive alpha,beta-unsaturated aldehyde which alkylates proteins and nucleic acids. Aldehyde generation required neutrophil activation and a free hydroxy-amino acid; it was inhibited by catalase and heme poisons, implicating H202 and myeloperoxidase in the cellular reaction. Aldehyde production by purified myeloperoxidase required H202 and chloride, and was mimicked by reagent hypochlorous acid (HOCl) in the absence of enzyme, suggesting that the reaction pathway involves a chlorinated intermediate. Collectively, these results indicate that the myeloperoxidase-H202-chloride system of phagocytes converts free hydroxy-amino acids into highly reactive alpha-hydroxy and alpha,beta-unsaturated aldehydes. The generation of glycolaldehyde, 2-hydroxypropanal, and acrolein by activated phagocytes may thus play a role in AGE product formation and tissue damage at sites of inflammation.


Assuntos
Acetaldeído/análogos & derivados , Acroleína/metabolismo , Aldeídos/metabolismo , Aminoácidos/metabolismo , Cloretos/metabolismo , Peróxido de Hidrogênio/metabolismo , Hidroxiácidos/metabolismo , Inflamação/metabolismo , Neutrófilos/enzimologia , Neutrófilos/metabolismo , Peroxidase/metabolismo , Acetaldeído/metabolismo , Catalase/farmacologia , Cromatografia Líquida de Alta Pressão , Reagentes de Ligações Cruzadas/metabolismo , Heme/metabolismo , Humanos , Ácido Hipocloroso/metabolismo , Lisina/análogos & derivados , Lisina/metabolismo , Espectrometria de Massas , Estrutura Molecular , Ativação de Neutrófilo , Oxirredução , Serina/metabolismo , Treonina/metabolismo
19.
J Pediatr Adolesc Gynecol ; 10(1): 13-7, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9061629

RESUMO

STUDY OBJECTIVE: To assess the utility of a history of smoking as a clinical indicator of substance use in pregnant adolescents. DESIGN: A secondary analysis of a subsample of all 15- to 19-year-old live-birth mothers (N = 1640) taken from the 1988 National Maternal and Infant Health Survey (NMIHS). Self-reported data were weighted and analyzed covering ethnicity, substance use, socioeconomic status, and prenatal care. Contingency table analysis and stepwise logistic regression were applied to compare the prevalence of other forms of substance use among smokers versus nonsmokers, and to evaluate whether a history of smoking made a unique contribution to identifying adolescents at increased risk for use of other substances. The specific substances studied were alcohol and cocaine which are known to be important contributors to perinatal morbidity and mortality. RESULTS: In this multiethnic, nationally representative subsample of pregnant adolescents, 35% reported a positive history of tobacco use 12 months before delivery. Another 32% had consumed alcohol, 9% had used marijuana, and about 1.5% had reported some use of cocaine or crack. The findings show greater use of tobacco by whites, non-Hispanics, the ever married, and women receiving prenatal care in the private sector. Fifty-three percent of all admitted users of alcohol or cocaine smoked cigarettes 12 months before delivery. Logistic regression shows that smokers were four times more likely to use alcohol or cocaine than nonsmokers when controlling for other sociodemographic and economic variables. CONCLUSION: Substance use is common in pregnant adolescents from all ethnic and economic backgrounds. Self-report of smoking may be useful in screening for adolescents at risk for using cocaine or alcohol during pregnancy.


Assuntos
Gravidez na Adolescência/psicologia , Fumar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/etnologia , Consumo de Bebidas Alcoólicas/psicologia , Distribuição de Qui-Quadrado , Cocaína , Feminino , Humanos , Modelos Logísticos , Fumar Maconha/epidemiologia , Fumar Maconha/etnologia , Fumar Maconha/psicologia , Gravidez , Gravidez na Adolescência/etnologia , Estudos Retrospectivos , Fatores de Risco , Assunção de Riscos , Fumar/etnologia , Fumar/psicologia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Inquéritos e Questionários , Estados Unidos
20.
J Cardiothorac Vasc Anesth ; 11(1): 10-2, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9058212

RESUMO

OBJECTIVES: Hemoglobin-based oxygen carriers will be used concurrently with intraoperative blood salvage. The effects of salvage and processing on blood containing one such solution (HBOC-201; Biopure Corp, Boston, MA) were studied. DESIGN: Prospective, randomized. SETTING: Laboratory. INTERVENTIONS: Sixteen blood units from healthy volunteers had either HBOC (1,500 mg/dL; n = 10) or normal saline (equivalent volume; n = 6) added. All units were salvaged and processed using a blood salvage device. Samples were analyzed for the concentration and molecular weight distribution of plasma hemoglobin and red cell morphology presalvage (pre) and following processing and washing (post 1). Five of the HBOC units underwent a second 1,000 mL wash (post 2). MEASUREMENTS AND MAIN RESULTS: Processing and washing decreased the concentration of plasma hemoglobin (mg/dL) in HBOC units (1311 +/- 265 pre to 27.8 +/- 19.6 post 1 to 6.5 +/- 2.19 post 2), but did not change the plasma hemoglobin concentration in saline units (2.05 +/- 1.27 pre v 3.18 +/- 0.79 post 1). Total plasma hemoglobin in HBOC units (6.56 +/- 2.19) was significantly greater than in saline units (3.18 +/- 0.79), even after the second wash (post 2). The concentration of unstable hemoglobin in the plasma phase was not different between groups. Red cell morphology was altered by the salvage process but was not different between groups. CONCLUSIONS: Salvage and processing of blood containing HBOC yield concentrated red cells that are indistinguishable from those obtained from blood without HBOC. Residual HBOC remains but is unchanged from the HBOC initially administered.


Assuntos
Substitutos Sanguíneos/farmacologia , Eritrócitos/efeitos dos fármacos , Transfusão de Sangue Autóloga/métodos , Equipamentos e Provisões , Hemoglobinas/química , Hemoglobinas/farmacologia , Humanos
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