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1.
Ecol Appl ; 19(6): 1628-44, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19769108

RESUMO

Nest predation may influence population dynamics of birds on the Arctic Coastal Plain (ACP) of Alaska, USA. Anthropogenic development on the ACP is increasing, which may attract nest predators by providing artificial sources of food, perches, den sites, and nest sites. Enhanced populations or concentrations of human-subsidized predators may reduce nest survival for tundra-nesting birds. In this study, we tested the hypothesis that nest survival decreases in proximity to human infrastructure. We monitored 1257 nests of 13 shorebird species and 619 nests of four passerine species at seven sites on the ACP from 2002 to 2005. Study sites were chosen to represent a range of distances to infrastructure from 100 m to 80 km. We used Cox proportional hazards regression models to evaluate the effects of background (i.e., natural) factors and infrastructure on nest survival. We documented high spatial and temporal variability in nest survival, and site and year were both included in the best background model. We did not detect an effect of human infrastructure on nest survival for shorebirds as a group. In contrast, we found evidence that risk of predation for passerine nests increased within 5 km of infrastructure. This finding provides quantitative evidence of a relationship between infrastructure and nest survival for breeding passerines on the ACP. A posteriori finer-scale analyses (within oil field sites and individual species) suggested that Red and Red-necked Phalaropes combined (Phalaropus fulicarius, P. lobatus) had lower productivity closer to infrastructure and in areas with higher abundance of subsidized predators. However, we did not detect such a relationship between infrastructure and nest survival for Semipalmated and Pectoral Sandpipers (Calidris pusilla, C. melanotos), the two most abundant shorebirds. High variability in environmental conditions, nest survival, and predator numbers between sites and years may have contributed to these inconsistent results. We recommend targeted management actions to minimize anthropogenic effects and suggest new research needed on this issue as expanding development is planned for the ACP of Alaska. In particular, we recommend research on demography of key predators and their importance with respect to nest survival, and experimental studies that better address challenges posed by high natural variability.


Assuntos
Aves , Ecossistema , Atividades Humanas , Comportamento Predatório , Alaska , Animais , Regiões Árticas , Humanos , Modelos Biológicos , Comportamento de Nidação
2.
Environ Monit Assess ; 134(1-3): 45-73, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17899420

RESUMO

Exxon Neftegas Limited, operator of the Sakhalin-1 consortium, is developing oil and gas reserves on the continental shelf off northeast Sakhalin Island, Russia. DalMorNefteGeofizika (DMNG), on behalf of the Sakhalin-1 consortium, conducted a 3-D seismic survey of the Odoptu license area during 17 August-9 September 2001. A portion of the primary known feeding area of the endangered western gray whale (Eschrichtius robustus) is located adjacent to the seismic block. The data presented here were collected as part of daily monitoring to determine if there was any measurable effect of the seismic survey on the distribution and abundance of western gray whales. Mitigation and monitoring program included aerial surveys conducted between 19 July and 19 November using the methodology outlined by the Southern California High Energy Seismic Survey team (HESS). These surveys provided documentation of the distribution, abundance and bottom feeding activity of western gray whales in relation to seismic survey sounds. From an operations perspective, the aerial surveys provided near real-time data on the location of whales in and outside the feeding area, and documented whether whales were displaced out of an area normally used as feeding habitat. The objectives of this study were to assess (a) temporal changes in the distribution and abundance of gray whales in relation to seismic survey, and (b) the influence of seismic survey, environmental factors, and other variables on the distribution and abundance of gray whales within their preferred feeding area adjacent to Piltun Bay. Multiple regression analysis revealed a limited redistribution of gray whales southward within the Piltun feeding area when the seismic survey was fully operational. A total of five environmental and other variables unrelated to seismic survey (date and proxies of depth, sea state and visibility) and one seismic survey-related variable (seg3d, i.e., received sound energy accumulated over 3 days) had statistically significant effects on the distribution and abundance of gray whales. The distribution of two to four gray whales observed on the surface (i.e., about five to ten whales in total) has likely been affected by the seismic survey. However, the total number of gray whales observed within the Piltun feeding area remained stable during the seismic survey.


Assuntos
Ecossistema , Ruído , Baleias , Acústica , Animais , Coleta de Dados , Indústrias Extrativas e de Processamento , Comportamento Alimentar , Petróleo , Densidade Demográfica , Análise de Regressão , Federação Russa
3.
Environ Monit Assess ; 134(1-3): 93-106, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17680334

RESUMO

Exxon Neftegas Limited, as operator of the Sakhalin-1 consortium, is developing oil and gas reserves on the continental shelf off northeast Sakhalin Island, Russia. DalMorNefteGeofizika (DMNG) on behalf of the Sakhalin-1 consortium conducted a 3-D seismic survey of the Odoptu license area during 17 August-9 September 2001. A portion of the primary feeding area of the endangered western gray whale (Eschrichtius robustus) is located in the vicinity of the seismic survey. This paper presents data to assess whether western gray whale bottom feeding activity, as indicated by visible mud plumes, was affected by seismic operations. The mitigation and monitoring program associated with the seismic survey included aerial surveys during 19 July-19 November 2001. These aerial surveys documented the local and regional distribution, abundance, and bottom feeding activity of western gray whales. Data on gray whale feeding activity before, during and after the seismic survey were collected, with the whales assumed to be feeding on the benthos if mud plumes were observed on the surface. The data were used to assess the influence of seismic survey and other factors (including environmental) on feeding activity of western gray whales. A stepwise multiple regression analysis failed to find a statistically significant effect (alpha = 0.05) of the seismic survey on frequency of occurrence of mud plumes of western gray whales used as a proxy to evaluate bottom feeding activity in Piltun feeding area. The regression indicated that transect number (a proxy for water depth, related to distance from shore) and swell height (a proxy for sea state) were the only variables that had a significant effect on frequency of whale mud plumes. It is concluded that the 2001 seismic survey had no measurable effect (alpha = 0.05) on bottom feeding activity of western gray whales off Sakhalin Island.


Assuntos
Comportamento Alimentar , Ruído , Baleias/fisiologia , Acústica , Animais , Coleta de Dados , Indústrias Extrativas e de Processamento , Sedimentos Geológicos , Petróleo , Federação Russa
5.
Vet Immunol Immunopathol ; 83(3-4): 203-11, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11730930

RESUMO

Mammary-associated serum amyloid A 3 (M-SAA3) was secreted at highly elevated levels in bovine, equine and ovine colostrum and found at lower levels in milk 4 days postparturition. N-terminal sequencing of the mature M-SAA3 protein from all the three species revealed a conserved four amino acid motif (TFLK) within the first eight residues. This motif has not been reported to be present in any of the hepatically-produced acute phase SAA (A-SAA) isoforms. Cloning of the bovine M-Saa3 cDNA from mammary gland epithelial cells revealed an open reading frame that encoded a precursor protein of 131 amino acids which included an 18 amino acid signal peptide. The predicted 113 residue mature M-SAA3 protein had a theoretical molecular mass of 12,826Da that corresponded with the observed 12.8kDa molecular mass obtained for M-SAA3 in immunoblot analysis. The high abundance of this extrahepatically produced SAA3 isoform in the colostrum of healthy animals suggests that M-SAA3 may play an important functional role associated with newborn adaptation to extrauterine life and possibly mammary tissue remodeling.


Assuntos
Colostro/química , Proteína Amiloide A Sérica/biossíntese , Motivos de Aminoácidos/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Bovinos , Cromatografia de Afinidade/veterinária , Colostro/imunologia , DNA/química , Eletroforese em Gel de Poliacrilamida/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Cavalos , Glândulas Mamárias Animais/metabolismo , Leite/química , Leite/imunologia , Dados de Sequência Molecular , Peso Molecular , Isoformas de Proteínas , RNA/química , RNA/isolamento & purificação , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Proteína Amiloide A Sérica/isolamento & purificação , Proteína Amiloide A Sérica/metabolismo , Ovinos
6.
Biochem Pharmacol ; 62(7): 963-74, 2001 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-11543732

RESUMO

Administration of bacterial lipopolysaccharide (LPS) to laboratory animals and cultured macrophages induces tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine. Pretreatment with Ginkgo biloba extract (EGb 761) inhibited the in vivo production of TNF-alpha (measured by ELISA) after challenge with LPS. To begin to understand the mechanism of this inhibition, we evaluated the in vitro effects of EGb 761 and its flavonoid component, quercetin, on LPS-treated RAW 264.7 macrophages. Pretreatment with EGb 761 or quercetin concentration-dependently inhibited TNF-alpha release, as measured by the L929 fibroblast assay. Northern blotting demonstrated that quercetin inhibited LPS-induced TNF-alpha mRNA, but did not alter its half-life. Activation of mitogen-activated protein kinases (MAPKs) and the redox-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1), are key events in the signal transduction pathways mediating TNF-alpha induction. Phosphorylation of extracellular signal-related kinases 1 and 2 (ERK 1/2), p38 MAPK, and Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), members of the MAPK family, was analyzed by western blotting. Our results suggest that quercetin is unique in its ability to inhibit TNF-alpha transcription by inhibiting the phosphorylation and activation of JNK/SAPK and, therefore, suppressing AP-1-DNA binding [assessed by electrophoretic mobility shift analysis (EMSA)]. Results from western analysis, EMSA, and transient transfections suggest that EGb 761 diminishes LPS-induced NF-kappaB but has no effect on LPS-induced TNF-alpha transcription. Both EGb 761 and quercetin inhibited ERK1/2 phosphorylation and p38 MAPK activity, which are important in the post-transcriptional regulation of TNF-alpha mRNA.


Assuntos
Antioxidantes/farmacologia , Flavonoides/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno , Extratos Vegetais , Quercetina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Fatores Ativadores da Transcrição , Animais , Proteínas Sanguíneas/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Células Cultivadas , DNA/efeitos dos fármacos , DNA/metabolismo , Interações Medicamentosas , Ginkgo biloba/química , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase 4 , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Plantas Medicinais , Antagonistas da Serotonina/farmacologia , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Proteínas Quinases p38 Ativadas por Mitógeno
7.
Obstet Gynecol ; 93(4): 504-9, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10214823

RESUMO

OBJECTIVE: To examine the relation between cervical dilatation and length and the risk of spontaneous preterm birth, including its subtypes preterm labor and preterm premature rupture of membranes (PROM). METHODS: Cervical dimensions assessed by clinical examination were recorded prospectively at 24-29 weeks' gestation in 871 subjects with singleton pregnancies who were followed to delivery. Relative risks (RRs) of preterm birth, preterm labor, and preterm PROM were calculated for clinically distinguishable categories of cervical dilatation and length and for cervical score (length minus dilatation). Regression analysis was used to adjust for confounding. Time to delivery from baseline examination was summarized using survival analysis. RESULTS: There were 73 spontaneous preterm births (8.3%), 46 preterm labors and 27 cases of preterm PROM. All cervical measurements were associated with increased risks of preterm birth, with increasing abnormality more strongly predictive of risk. The adjusted RR for preterm birth with dilatation of at least 0.5 cm was 2.9 (95% confidence interval [CI] 1.2, 7.3); for length of 1.5 cm or less, the RR was 2.1 (95% CI 1.0, 4.5), and for cervical score less than 2.0, the RR was 2.8 (95% CI 1.4, 5.6). The association with cervical measurements was stronger for preterm PROM than for preterm labor, although precision was limited. These measurements had high specificity (93-99%) and low sensitivity (8-20%) for predicting preterm birth. CONCLUSION: In asymptomatic women at 24-29 weeks' gestation, greater cervical dilatation and shorter length were associated with increased risk of spontaneous preterm delivery, particularly preterm PROM.


Assuntos
Colo do Útero/anatomia & histologia , Ruptura Prematura de Membranas Fetais/epidemiologia , Primeira Fase do Trabalho de Parto , Trabalho de Parto Prematuro/epidemiologia , Adulto , Antropometria , Feminino , Humanos , Gravidez , Estudos Prospectivos , Risco
8.
Alcohol Clin Exp Res ; 22(8): 1731-9, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9835288

RESUMO

Recent studies have shown that the alcohol metabolites malondialdehyde and acetaldehyde can combine to form a stable adduct (MAA) on proteins. This adduct has been detected in the livers of rats chronically consuming ethanol, and serum antibodies to MAA have been observed at significantly higher concentrations in ethanol-fed when compared with pair-fed or chow-fed control rats. More recently, preliminary studies have strongly suggested that the MAA adduct is capable of stimulating antibody responses to soluble proteins in the absence of adjuvants. The antibodies produced recognize either the MAA epitope or the carrier protein itself. Therefore, it was the purpose of this study to examine the potential immunogenicity of MAA-modified exogenous proteins in the absence of adjuvants. Balb/c mice were immunized in the presence or absence of adjuvant with different concentrations of unmodified or MAA-modified proteins. The antibody response to both the MAA epitope and unmodified protein epitopes were determined by ELISA. In the absence of adjuvant, significant antibody responses were induced to both the MAA epitope and nonmodified protein epitopes. Smaller immunizing doses of MAA-protein conjugate favored the production of antibodies to nonmodified proteins, whereas larger doses induced a strong anti-MAA response. In studies to begin determining a mechanism for the specificity of the response in the absence of adjuvants, peritoneal macrophages were found to bind and degrade MAA-adducted proteins through the use of a scavenger receptor. This indicated that MAA-adducted proteins may be specifically taken up and epitopes presented to the humoral immune system in the absence of adjuvants. Importantly, these are the first data showing that an alcohol-related metabolite can induce an antibody response in the absence of adjuvant and suggesting a mechanism by which antibody to the MAA adduct or its carrier (exogenous or endogenous) proteins may be generated in vivo.


Assuntos
Acetaldeído/farmacologia , Doenças Autoimunes/imunologia , Proteínas Sanguíneas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/farmacologia , Acetaldeído/imunologia , Animais , Autoanticorpos/sangue , Proteínas Sanguíneas/imunologia , Relação Dose-Resposta a Droga , Feminino , Peroxidação de Lipídeos/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Malondialdeído/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ratos
9.
Biochem Pharmacol ; 56(11): 1515-23, 1998 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-9827586

RESUMO

Studies have investigated the hypothesis that metabolically derived acetaldehyde (AA) is capable of complexing with liver cell proteins to form AA-protein adducts that are capable of acting as antigens and inducing an immune response, as detected by the formation of unique antibodies. In an effort to better characterize and describe these adducts, mouse monoclonal and rabbit polyclonal antibodies specific for antigens prepared with AA under non-reducing (physiologic) and reducing (presence of sodium cyanoborohydride) conditions have been prepared. Two monoclonal antibodies were developed. The first antibody was RT1.1, which is specific to N-ethyl lysine (NEL); it is of the IgG2b isotype and recognizes all proteins modified with AA under reducing conditions. The other monoclonal antibody, NR-1, was of the IgG3 isotype; it recognizes proteins modified with AA under non-reducing conditions and cannot be inhibited by NEL. Affinity-purified and/or absorbed polyclonal antibodies were also produced to these epitopes. Using this panel of monoclonal and affinity-purified polyclonal antibodies, unique antigen-antibody binding occurred that: (1) detected only NEL; (2) reacted with the alpha-amino group on proteins prepared under reducing conditions; and (3) detected adducts on proteins prepared under non-reducing conditions. However, the only antibodies that recognized antigen(s) from alcohol-fed rat livers were those that were not specific to NEL or the alpha-amino group modified under reducing conditions. These data indicate that the relevant adduct in alcohol-fed rat livers is not NEL, and that it presumably is related to proteins modified with AA under non-reducing conditions.


Assuntos
Acetaldeído/metabolismo , Fígado/metabolismo , Proteínas/metabolismo , Acetaldeído/análise , Alcoolismo/metabolismo , Animais , Anticorpos , Anticorpos Monoclonais , Especificidade de Anticorpos , Antígenos/análise , Citosol/metabolismo , Lisina , Camundongos , Camundongos Endogâmicos BALB C , Proteínas/imunologia , Coelhos , Ratos , Ratos Sprague-Dawley
10.
Am J Perinatol ; 14(9): 553-4, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9394165

RESUMO

The objective of this study was to compare patients' hospital course, complications, and charges for oral and intravenous (i.v.) desensitization regimens for the treatment of syphilis in the penicillin-allergic gravida. We performed a retrospective search of medical records at two tertiary-level teaching hospitals and reviewed the hospital course of penicillin-allergic gravidas who underwent penicillin desensitization. Between August 1988 and December 1995, 16 procedures for penicillin desensitization were carried out: 11 oral procedures, and 6 i.v. procedures. There were no significant differences between the patients in the oral and i.v. desensitization groups with respect to demographic characteristics, duration of time in a monitored bed, or length of hospital stay. The oral regimen was less expensive than the i.v. regimen ($144.06 vs. $319.48). In our experience, oral and i.v. regimens provide effective desensitization for the treatment of syphilis in penicillin-allergic gravidas. However, the oral route offers ease of administration and substantial cost savings, making it the preferred method.


Assuntos
Hipersensibilidade a Drogas , Penicilinas/administração & dosagem , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sífilis/tratamento farmacológico , Administração Oral , Feminino , Humanos , Injeções Intravenosas , Penicilinas/economia , Penicilinas/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/economia , Estudos Retrospectivos , Sífilis/economia
11.
Biochem Pharmacol ; 48(1): 183-9, 1994 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-8043021

RESUMO

A monoclonal antibody has been developed that recognizes only protein-acetaldehyde (AA) adducts prepared under reducing conditions: 5 mM AA with 30 mM sodium cyanoborohydride overnight at 37 degrees. This monoclonal antibody is a mouse IgG2b that has been designated RT1.1. The primary adduct formed when proteins are exposed to acetaldehyde under reducing conditions is N-ethyl lysine (NEL). To examine the epitope specificity of RT1.1, inhibition ELISAs were developed using NEL and other possible inhibitors, such as arginine, ethylamine, lysine and proteins modified with AA under non-reducing conditions. RT1.1 (at half-maximum optical density, 50 ng/mL) was inhibited only by NEL and was independent of the carrier or the pH of the buffer used in the ELISA. Further evidence indicating that NEL is the epitope recognized by RT1.1 was obtained using mouse and human epidermal growth factor (EGF). Both proteins contain one alpha amino group but only the human-EGF contains lysine residues with epsilon amino groups. In experiments where these two proteins were modified with AA under reducing conditions, RT1.1 reacted only with human-EGF. These studies demonstrate that RT1.1 is specific for NEL that is formed by the ethylation of proteins with acetaldehyde under reducing conditions. Additionally, these studies demonstrate that the procedures and methods used herein may be useful for characterizing other antibodies prepared to AA-modified proteins under a variety of defined in vitro chemical conditions.


Assuntos
Acetaldeído/química , Anticorpos Monoclonais/imunologia , Especificidade de Anticorpos , Lisina/imunologia , Tubulina (Proteína)/imunologia , Animais , Bovinos , Lisina/análogos & derivados , Camundongos , Oxirredução , Tubulina (Proteína)/química
12.
Alcohol Clin Exp Res ; 18(1): 164-71, 1994 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8198215

RESUMO

Acetaldehyde (AA), the major product of alcohol metabolism, has been shown to bind to proteins in vivo and form chemical adducts. These AA-protein adducts have been shown to alter protein structure and function and may result in tissue damage. Recent reports have shown that polyclonal antibodies can be produced that recognize proteins modified in vitro with AA in the presence of sodium cyanoborohydride (NaCNBH3), a strong reducing (R) agent. Antibodies prepared in this way have been shown to recognize proteins in the livers of rats fed alcohol chronically. Because multiple AA-protein adducts can be recognized by polyclonal antisera, and a variety of adducts may be formed in vitro or in vivo, this study was designed to develop monoclonal antibodies specific for proteins modified by AA. In addition, adducts formed under R conditions are probably chemically different than those formed under nonreducing (NR) conditions, and monoclonal antibodies may provide the specificity required to distinguish these chemical differences. Balb/c mice were immunized with bovine brain tubulin that was modified by treatment with 5 mM AA for 7 days under NR conditions. Sera from immunized animals were tested for antibody activity to the immunogen (protein-NR) and for cross-reactivity to protein-R and unmodified protein. Although the highest serum antibody titers were seen toward the NR adduct, antibodies to the R adduct were also detected. This activity difference was independent of the carrier protein, because NR and R bovine serum albumin, keyhole limpet hemocyanin, and actin also gave similar results when used as the adducted protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Acetaldeído/metabolismo , Anticorpos Monoclonais , Proteínas/metabolismo , Alcoolismo/metabolismo , Animais , Especificidade de Anticorpos , Bovinos , Citosol/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ligação Proteica/fisiologia , Coelhos , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/metabolismo
13.
J Public Health Policy ; 15(2): 203-17, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8063900

RESUMO

This paper discusses the process used to develop an environmental health addendum to the Assessment Protocol for Public Health (APEX/PH). Local health departments in Washington State are undertaking a trial program utilizing APEX/PH. The environmental health addendum was developed in response to the paucity of environmental health-oriented data requested in APEX/PH, Part II, the Community Process, and includes environmental exposure indicators as well as health status indicators. The methods used to gain a consensus among key environmental health professionals in Washington State are discussed and an environmental issue prioritization scheme is recommended. The need for the environmental health addendum and future work on the addendum and APEX/PH are discussed.


Assuntos
Saúde Ambiental , Saúde Pública , Política de Saúde , Humanos , Estados Unidos
14.
NLN Publ ; (19-2546): 97-122, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8152896
15.
Proc Natl Acad Sci U S A ; 90(13): 6125-9, 1993 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-7687060

RESUMO

We have examined components of the preintegration complex of human immunodeficiency virus type 1 (HIV-1) and have analyzed features which govern the association of these components. HIV-1 nucleoprotein complexes, isolated from nuclear and cytoplasmic extracts of CD4+ cells after acute virus infection, contained viral RNA and DNA in association with viral matrix (MA), integrase (IN), and reverse transcriptase (RT) antigens but not capsid (CA) antigens and possessed integration activity in vitro. Association of IN but not RT or MA antigens with viral DNA was detergent-stable. Analysis of viral DNA synthesis and nuclear import of viral nucleoprotein complexes in the presence of a reversible RT inhibitor demonstrated that reverse transcription of viral RNA could be completed entirely in the host cell nucleus. Our studies demonstrate structural and functional features of the nucleoprotein (preintegration) complex of HIV-1 which are pertinent to the understanding of early events in the lentiviral life cycle.


Assuntos
Linfócitos T CD4-Positivos/microbiologia , DNA Nucleotidiltransferases/metabolismo , DNA Viral/metabolismo , HIV-1/fisiologia , DNA Polimerase Dirigida por RNA/metabolismo , Proteínas da Matriz Viral/metabolismo , Sequência de Bases , Núcleo Celular/metabolismo , DNA Viral/biossíntese , Transcriptase Reversa do HIV , HIV-1/enzimologia , Humanos , Integrases , Dados de Sequência Molecular , RNA Viral/metabolismo , Transcrição Gênica , Integração Viral , Replicação Viral
16.
J Am Acad Dermatol ; 28(5 Pt 1): 691-5, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8496412

RESUMO

BACKGROUND: Little is understood about reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin. OBJECTIVE: Our purpose was to define reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin further with focus on immunologic studies. METHODS: In patients with reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin, we measured circulating immune complexes before, during, and after therapy. We examined natural killer cells in a functional assay; we performed direct immunofluorescence and T- and B-cell marker studies in skin biopsy specimens. RESULTS: The infiltrate in reticular erythematous mucinosis is composed of helper T cells. Circulating immune complexes are increased in both reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin and decrease with hydroxychloroquine therapy and clinical clearing. Natural killer cell function is decreased in reticular erythematous mucinosis and Jessner's lymphocytic infiltrate of skin. CONCLUSION: Changes in circulating immune complex titers accompanying therapy with hydroxychloroquine and clinical clearing, with recurrence of the condition and increase in circulating immune complexes on discontinuation of treatment, point to a possible relation between these events.


Assuntos
Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Mucinoses/imunologia , Mucinoses/patologia , Dermatopatias Papuloescamosas/imunologia , Dermatopatias Papuloescamosas/patologia , Adulto , Idoso , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Complexo Antígeno-Anticorpo/análise , Vasos Sanguíneos/patologia , Eritema , Feminino , Cabelo/patologia , Humanos , Hiperplasia , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Ativadas por Linfocina/patologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Linfócitos/imunologia , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia
17.
Cancer Res ; 53(8): 1921-8, 1993 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-8385575

RESUMO

Earlier reports from our laboratory showed that Abelson virus-induced, highly malignant and liver metastatic RAW117-H10 cells, but not the parental, less metastatic RAW117-P cells, inhibited both T-cell and B-cell mitogen-induced proliferation of syngeneic normal murine spleen cells. Similar inhibition was also noted when RAW117-H10 cell surface molecules extracted with butanol were used instead of whole tumor cells. In this report we describe the suppressive properties of the butanol-extracted RAW117-H10 cell surface molecules on other immune functions and the isolation/purification of a molecule from RAW117-H10 cell butanol extract which shows inhibitory activity. The immunosuppressive molecules also inhibit natural killer cell-mediated cytotoxicity, lymphokine-activated killer cell-mediated cytotoxicity, and bone marrow colony-forming unit-granulocyte-macrophage colony formation, but not colony-forming unit-fibroblast colony formation. The suppressive molecules inhibit interleukin 2 production by the T-lymphocytes. One of the molecules responsible for some of the immunosuppressive activity has been isolated and purified from butanol extracts of the metastatic RAW117-H10 cells by preparative isoelectrofocusing techniques. The suppressive molecule has an isoelectric point of 4.3 with an approximate molecular weight of 70,000. Metastatic RAW117-H10 lymphoma cells therefore express immunosuppressive molecules, which may facilitate their growth and metastasis in vivo.


Assuntos
Imunossupressores/isolamento & purificação , Linfoma/imunologia , Animais , Citotoxicidade Imunológica/efeitos dos fármacos , Imunossupressores/farmacologia , Interleucina-2/biossíntese , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/imunologia , Vírus da Leucemia Felina/patogenicidade , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Metástase Neoplásica , Células Tumorais Cultivadas
18.
Pediatr Nephrol ; 7(1): 6-10, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8439480

RESUMO

The relationship of IgG- and IgM-bound circulating immune complexes and immune dysfunction to glomerular injury was evaluated in 15 children with end-stage liver disease (ESLD) awaiting liver transplantation. Compared with age-matched controls, children with ESLD had significantly (P < 0.01) increased serum IgG, IgA, and IgM levels, as well as IgG- and IgM-bound circulating immune complexes. Furthermore, they showed a significant (P < 0.05) depression of C3 and C4 levels compared with controls. Hematuria occurred in 66% of children with ESLD, and the urinary protein/creatinine ratio was also significantly (P < 0.01) increased compared with controls (4.65 +/- 2.56 vs. 0.16 +/- 0.04 mg/mg). Light microscopy of renal biopsy tissue obtained from 6 children with ESLD at the time of transplantation demonstrated mesangial proliferation and expansion with basement membrane splitting. This was associated with subendothelial deposits on electron-microscopic examination, compatible with a diagnosis of membranoproliferative glomerulonephritis. By immunofluorescence, deposition of IgG, IgA, and IgM occurred in various combinations with co-deposition of complement fragments. We conclude that membranoproliferative glomerulonephritis is a common finding in children with ESLD, probably due to entrapment of circulating IgG- and IgM-bound immune complexes.


Assuntos
Complexo Antígeno-Anticorpo/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Nefropatias/patologia , Glomérulos Renais/patologia , Hepatopatias/patologia , Criança , Pré-Escolar , Doença Crônica , Creatinina/urina , Imunofluorescência , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Hematúria/patologia , Humanos , Lactente , Nefropatias/sangue , Nefropatias/complicações , Glomérulos Renais/imunologia , Glomérulos Renais/ultraestrutura , Hepatopatias/sangue , Hepatopatias/complicações , Proteinúria/patologia
19.
Clin Exp Immunol ; 90(2): 293-9, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1424289

RESUMO

The hepatic production of the acute phase proteins in response to inflammatory cytokines, and the interaction of corticosteroids within this response, has been the subject of considerable recent research. In this study we have examined the effects of the corticosteroid prednisolone on the production of IL-1 alpha and IL-1 beta by lipopolysaccharide (LPS)-stimulated monocytes, and the ability of the monocyte conditioned media (MOCM) obtained under these conditions to induce human hepatoma HepG2 cells to produce serum amyloid A (SAA) and C-reactive protein (CRP). We also examined the production of SAA and CRP by HepG2 cells exposed to different combinations and concentrations of recombinant human (rh) IL-1 alpha, rhIL-1 beta, rhIL-6, recombinant human tumour necrosis factor-alpha (rhTNF-alpha) and prednisolone. The findings indicate: (i) prednisolone substantially inhibits the production of both IL-1 alpha and IL-1 beta by LPS-stimulated monocytes. The MOCM from prednisolone-treated monocytes induced less SAA and CRP production by HepG2 cells; (ii) IL-1 alpha and IL-1 beta both induced CRP and SAA synthesis by HepG2 cells, but only in the presence of IL-6. IL-1 beta was the more potent inducer for SAA production, but for CRP production IL-1 alpha and IL-1 beta were equivalent; (iii) prednisolone enhances the production of SAA by HepG2 cells, but does not enhance the production of CRP; (iv) TNF-alpha in the presence or absence of IL-6 and/or prednisolone did not induce the production of SAA or CRP by HepG2 cells. These findings offer a tenable solution to a disparate production of SAA compared with CRP in corticosteroid-treated cystic fibrosis (CF) patients.


Assuntos
Proteína C-Reativa/biossíntese , Citocinas/administração & dosagem , Interleucina-1/administração & dosagem , Fígado/metabolismo , Monócitos/fisiologia , Prednisolona/farmacologia , Proteína Amiloide A Sérica/biossíntese , Meios de Cultura , Humanos , Interleucina-1/biossíntese , Interleucina-6/farmacologia , Proteínas Recombinantes/farmacologia , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/farmacologia
20.
J Clin Lab Anal ; 6(4): 219-24, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1403341

RESUMO

Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830 serum samples from 155 cystic fibrosis (CF) patients. Correlation coefficients were calculated for all samples (r = 0.73), for samples from non-corticosteroid treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid treated (CFS) patients (n = 132, r = 0.35). SAA was the more sensitive indicator of pulmonary inflammation when SAA and CRP were compared to pulmonary function tests of 49 hospitalized patients at admission and discharge. CRP levels were significantly (p less than .05) lower at admission in CFS patients than in CFNS patients, whereas SAA levels were not significantly different between the two groups. All nine CFS patients hospitalized had elevated SAA levels (average 22 times above normal limits) at admission, while only six had elevated CRP levels (average 3.7 times above normal limits) at admission. In the 40 CFNS patients both SAA and CRP levels were significantly elevated at admission. In each case SAA and CRP levels declined as pulmonary functions improved with effective antimicrobial therapy. In three instances SAA levels increased during hospitalization while CRP levels did not. In each case, rising SAA levels indicated clinical deterioration associated with evolving resistance of P. aeruginosa which required a change in antibiotic therapy.


Assuntos
Proteína C-Reativa/metabolismo , Fibrose Cística/sangue , Proteína Amiloide A Sérica/metabolismo , Adolescente , Corticosteroides/uso terapêutico , Adulto , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Feminino , Humanos , Masculino , Pneumonia/sangue , Pneumonia/complicações , Pneumonia/fisiopatologia , Infecções por Pseudomonas/sangue , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/fisiopatologia , Testes de Função Respiratória
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