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1.
Injury ; 53(12): 4104-4113, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36424690

RESUMO

BACKGROUND: High energy open tibial fractures are complex injuries with no consensus on the optimal method of fixation. Treatment outcomes are often reported with union and re-operation rates, often without specific definitions being provided.  We sought to describe union, reoperation rates, and patient reported outcomes, using the validated EQ-VAS and Disability Rating Index (DRI) scores, following stabilisation with a Taylor Spatial Frame (TSF) and a combined orthoplastic approach for the management of soft tissues. A literature review is also provided. METHOD: A prospective cross-sectional follow up of open tibial fractures, treated at a level 1 major trauma centre, managed with a TSF using a one ring per segment technique between January 2014 and December 2019 were identified. Demographic, injury and operative data were recorded, along with Patient Reported Outcome Measures (PROM) scores, specifically the EQ-VAS and Disability Rating Index (DRI). Union rates, defined by radiographic union scale in tibia (RUST) scores, and re-operation rates were recorded. Appropriate statistical analyses were performed, with a p<0.05 considered statistically significant. RESULTS: Overall, 51 patients were included. Mean age was 51.2 ± 17.4 years, with a 4:1 male preponderance. Diaphyseal and distal fractures accounted for 76% of cases. Mean time in frame was 206.7 ± 149.4 days. Union was defined and was achieved in 41/51 (80.4%) patients. Deep infection occurred in 6/51 (11.8%) patients. Amputation was performed in 1 case (1.9%). Overall re-operation rate was 33%. Time to union were significantly longer if re-operation was required for any reason (uncomplicated 204±189 vs complicated 304±155 days; p = 0.0017) . EQ-VAS and DRI scores significantly deteriorated at 1 year follow-up (EQVAS 87.5 ± 11.7 vs 66.5 ± 20.4;p<0.0001 and DRI 11.9 ± 17.8 vs 39.3 ± 23.3;p<0.0001). At 1 year post op, 23/51(45.1%) required a walking aid, and 17/29 (58.6%) of those working pre-injury had returned to work. CONCLUSION: Open tibial fracture have significant morbidity and long recovery periods as determined by EQVAS and DRI outcome measures.  We report the largest series of open tibial feature treated primarily with a TSF construct, which has similar outcomes to other techniques, and should therefore be considered as a useful technique for managing these injuries.


Assuntos
Fraturas Expostas , Fraturas da Tíbia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Fraturas Expostas/cirurgia , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia
2.
Sci Rep ; 8(1): 17026, 2018 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-30451923

RESUMO

Altered lipid metabolism is a feature of chronic inflammatory disorders. Increased plasma lipids and lipoproteins have been associated with multiple sclerosis (MS) disease activity. Our objective was to characterise the specific lipids and associated plasma lipoproteins increased in MS and to test for an association with disability. Plasma samples were collected from 27 RRMS patients (median EDSS, 1.5, range 1-7) and 31 healthy controls. Concentrations of lipids within lipoprotein sub-classes were determined from NMR spectra. Plasma cytokines were measured using the MesoScale Discovery V-PLEX kit. Associations were tested using multivariate linear regression. Differences between the patient and volunteer groups were found for lipids within VLDL and HDL lipoprotein sub-fractions (p < 0.05). Multivariate regression demonstrated a high correlation between lipids within VLDL sub-classes and the Expanded Disability Status Scale (EDSS) (p < 0.05). An optimal model for EDSS included free cholesterol carried by VLDL-2, gender and age (R2 = 0.38, p < 0.05). Free cholesterol carried by VLDL-2 was highly correlated with plasma cytokines CCL-17 and IL-7 (R2 = 0.78, p < 0.0001). These results highlight relationships between disability, inflammatory responses and systemic lipid metabolism in RRMS. Altered lipid metabolism with systemic inflammation may contribute to immune activation.


Assuntos
Pessoas com Deficiência , Lipoproteínas/sangue , Esclerose Múltipla/sangue , Esclerose Múltipla/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
J Clin Psychol ; 73(12): 1612-1628, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28249107

RESUMO

OBJECTIVE: We conducted a controlled randomized preliminary trial of a modified dissonance-based eating disorder program (n = 24) compared to an assessment-only control condition (n = 23) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 47) with clinical (n = 22) and subclinical (n = 25) eating disorder symptoms. METHOD: The traditional content of the Body Project, a dissonance-based eating disorder prevention program, was modified to include verbal, written, and behavioral exercises designed to dissuade self-objectification and maladaptive social comparison. Women with clinical and subclinical symptoms were included in the target audience to investigate both the treatment and the indicated prevention utility of the modified dissonance program. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, and eating disorder symptoms were evaluated in the control and the modified dissonance condition at baseline, postintervention, and 2-month follow-up. RESULTS: We predicted a statistically significant 2 (condition: control, modified dissonance) x 3 (time: baseline, postintervention, 2-month follow-up) interaction in the mixed factorial multivariate analyses of variance results. Results confirmed this hypothesis. Eating disorder risk factors and symptoms decreased significantly among participants in the modified dissonance condition at postintervention and 2-month follow-up compared to baseline; symptom improvement was greater among participants in the modified compared to the control condition. A secondary analysis indicated symptom improvement did not vary as a function of symptom status (clinical, subclinical), suggesting the program is efficacious in both indicated prevention and treatment applications. CONCLUSION: Results provide preliminary support for the modified dissonance program.


Assuntos
Imagem Corporal , Terapia Cognitivo-Comportamental/métodos , Dissonância Cognitiva , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Avaliação de Resultados em Cuidados de Saúde , Autoimagem , Percepção Social , Adolescente , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Feminino , Seguimentos , Humanos , Projetos Piloto , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
4.
EBioMedicine ; 9: 257-277, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27333023

RESUMO

Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism controlling the expression of SCN1A that is mediated by an antisense non-coding RNA (SCN1ANAT). Using oligonucleotide-based compounds (AntagoNATs) targeting SCN1ANAT we were able to induce specific upregulation of SCN1A both in vitro and in vivo, in the brain of Dravet knock-in mouse model and a non-human primate. AntagoNAT-mediated upregulation of Scn1a in postnatal Dravet mice led to significant improvements in seizure phenotype and excitability of hippocampal interneurons. These results further elucidate the pathophysiology of Dravet syndrome and outline a possible new approach for the treatment of this and other genetic disorders with similar etiology.


Assuntos
Encéfalo/metabolismo , Epilepsias Mioclônicas/patologia , Canal de Sódio Disparado por Voltagem NAV1.1/metabolismo , RNA Longo não Codificante/metabolismo , Alelos , Animais , Sequência de Bases , Comportamento Animal , Encéfalo/diagnóstico por imagem , Linhagem Celular , Chlorocebus aethiops , Modelos Animais de Doenças , Eletroencefalografia , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/metabolismo , Expressão Gênica , Técnicas de Introdução de Genes , Hipocampo/fisiologia , Humanos , Técnicas In Vitro , Interneurônios/metabolismo , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Canal de Sódio Disparado por Voltagem NAV1.1/química , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Conformação de Ácido Nucleico , Oligonucleotídeos Antissenso/metabolismo , Técnicas de Patch-Clamp , Fenótipo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Análise de Sequência de RNA , Temperatura , Regulação para Cima , Células Vero , Gravação em Vídeo
5.
Mol Biol Evol ; 28(3): 1141-55, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21059793

RESUMO

Sensing the environment and responding appropriately to it are key capabilities for the survival of an organism. All extant organisms must have evolved suitable sensors, signaling systems, and response mechanisms allowing them to survive under the conditions they are likely to encounter. Here, we investigate in detail the evolutionary history of one such system: The phage shock protein (Psp) stress response system is an important part of the stress response machinery in many bacteria, including Escherichia coli K12. Here, we use a systematic analysis of the genes that make up and regulate the Psp system in E. coli in order to elucidate the evolutionary history of the system. We compare gene sharing, sequence evolution, and conservation of protein-coding as well as noncoding DNA sequences and link these to comparative analyses of genome/operon organization across 698 bacterial genomes. Finally, we evaluate experimentally the biological advantage/disadvantage of a simplified version of the Psp system under different oxygen-related environments. Our results suggest that the Psp system evolved around a core response mechanism by gradually co-opting genes into the system to provide more nuanced sensory, signaling, and effector functionalities. We find that recruitment of new genes into the response machinery is closely linked to incorporation of these genes into a psp operon as is seen in E. coli, which contains the bulk of genes involved in the response. The organization of this operon allows for surprising levels of additional transcriptional control and flexibility. The results discussed here suggest that the components of such signaling systems will only be evolutionarily conserved if the overall functionality of the system can be maintained.


Assuntos
Escherichia coli K12/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Evolução Molecular , Transativadores/genética , Transativadores/metabolismo , Sequência de Bases , Escherichia coli K12/metabolismo , Proteínas de Escherichia coli/classificação , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Estudos de Associação Genética , Genoma Bacteriano , Instabilidade Genômica/fisiologia , Genômica , Óperon , Filogenia , Estresse Fisiológico/fisiologia , Transativadores/classificação , Transcrição Gênica
6.
Am J Hum Genet ; 66(6): 1845-56, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10775531

RESUMO

Coronary heart disease (CHD) accounts for half of the 1 million deaths annually ascribed to cardiovascular disease and for almost all of the 1.5 million acute myocardial infarctions. Within families affected by early and apparently heritable CHD, dyslipidemias have a much higher prevalence than in the general population; 20%-30% of early familial CHD has been ascribed to primary hypoalphalipoproteinemia (low HDL-C). This study assesses the evidence for linkage of low HDL-C to chromosomal region 11q23 in 105 large Utah pedigrees ascertained with closely related clusters of early CHD and expanded on the basis of dyslipidemia. Linkage analysis was performed by use of 22 STRP markers in a 55-cM region of chromosome 11. Two-point analysis based on a general, dominant-phenotype model yielded LODs of 2.9 for full pedigrees and 3.5 for 167 four-generation split pedigrees. To define a localization region, model optimization was performed using the heterogeneity, multipoint LOD score (mpHLOD). This linkage defines a region on 11q23.3 that is approximately 10 cM distal to-and apparently distinct from-the ApoAI/CIII/AIV gene cluster and thus represents a putative novel localization for the low HDL-C phenotype.


Assuntos
Cromossomos Humanos Par 11/genética , Doença de Tangier/genética , HDL-Colesterol/metabolismo , Mapeamento Cromossômico , Feminino , Genes Dominantes/genética , Heterogeneidade Genética , Genótipo , Humanos , Escore Lod , Masculino , Repetições de Microssatélites/genética , Modelos Genéticos , Linhagem , Penetrância , Doença de Tangier/metabolismo , Utah
7.
Dis Aquat Organ ; 40(1): 67-78, 2000 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-10785864

RESUMO

Pteriid oysters (Pinctada maxima, Pinctada margaritifera, Pinctada albina, Pteria penguin), rock oysters (Saccostrea glomerata, Saccostrea cuccullata, Saccostrea echinata) and representatives of other taxa (Malleidae, Isognomonidae, Pinnidae, Mytilidae, Spondylidae, Arcidae) from the wild, and 4670 hatchery-reared P. maxima, from northern and Western Australia, were examined for parasites and diseases. Rickettsiales-like inclusions and metacestodes of Tylocephalum occurred in most species. Intranuclear virus-like inclusions occurred in 1/415 wild P. maxima, 1/1254 S. cuccullata, 3/58 Isognomon isognomum, 1/80 Pinna bicolor and 1/45 Pinna deltodes. Perkinsus was histologically observed in 1/4670 P. maxima spat, 2/469 P. albina, 1/933 S. glomerata, 16/20 Malleus meridianus, 12/58 I. isognomum, 1/45 P. deltodes, 5/12 Spondylus sp., 1/16 Septifer bilocularis and 3/6 Barbatia helblingii. One of 1254 S. cuccullata was heavily systematically infected with Perkinsus merozoites, meronts and schizonts, and was patently diseased. Other potentially serious pathogens included Haplosporidium sp. in 6/4670 P. maxima spat, Marteilia sydneyi from 1/933 S. glomerata, and Marteilia sp. (probably M. lengehi) (1/1254) and Haplosporidium sp. (125/1254) from S. cuccullata. The latter were associated with epizootics on offshore islands, with heaviest prevalence (45%) in oysters with empty gonad follicles. Marteilioides sp. infected the oocytes of 9/10 female S. echinata from Darwin Harbour. Details of geographical distribution and pathology are given, and the health of the bivalves examined is discussed.


Assuntos
Moluscos/parasitologia , Animais , Austrália/epidemiologia , Reservatórios de Doenças , Transmissão de Doença Infecciosa , Feminino , Ostreidae/parasitologia , Doenças Parasitárias em Animais/epidemiologia , Doenças Parasitárias em Animais/transmissão , Frutos do Mar
8.
Arterioscler Thromb Vasc Biol ; 20(4): 1089-93, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10764678

RESUMO

Clinical familial hypercholesterolemia has been shown to result from mutations in 2 genes, the low density lipoprotein (LDL) receptor on chromosome 19 and apolipoprotein B on chromosome 2. However, we have recently described a Utah pedigree in which linkage to both genes was clearly excluded. A multipoint linkage analysis of 583 markers genotyped on 31 (18 affected) members of this pedigree was undertaken to localize a genetic region that may harbor a third gene that could result in clinical familial hypercholesterolemia. A multipoint log of the odds score of 6.8 was obtained for markers on 1p32. Haplotype carriers and affected status are completely concordant (18/18 persons). The phenotype is also expressed in young children (ages 4 and 9). Specific recombinant individuals in the pedigree restrict the region of linkage to an approximately 17 cM interval between polymorphic markers D1S2130 and D1S1596. This region appears to overlap the region found linked to severe hypercholesterolemia in French and Spanish families. The identification of the gene in this region may provide important pathophysiological insights into new mechanisms that may lead to highly elevated LDL cholesterol and other associated dyslipidemic phenotypes.


Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 1 , Hipercolesterolemia/genética , Adolescente , Adulto , Apolipoproteínas B/genética , Feminino , Haplótipos , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores de LDL/genética , Utah
9.
J Adv Nurs ; 32(6): 1514-21, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11136421

RESUMO

This paper outlines a stage-by-stage framework for the analysis of data obtained from qualitative semistructured diaries. As the framework for analysis was developed, it became apparent that the methodological problem of verifying the initial analysis, required serious consideration. The research literature available was found simply to identify the difficulty, but offered no solutions. Recognizing that trustworthiness is a hallmark of qualitative research, a data analysis verification tool (DAViT) was designed. This proved to be extremely effective in enhancing the trustworthiness of a qualitative study in a number of ways. The analysis framework and verification tool together offers an eclectic approach for qualitative diary data analysis. It is further advocated that they are amenable to the analysis and verification of qualitative data obtained from semistructured interviews.


Assuntos
Coleta de Dados/métodos , Prontuários Médicos , Pesquisa em Enfermagem/métodos , Interpretação Estatística de Dados , Cuidado Periódico , Feminino , Humanos , Mães/psicologia , Poder Psicológico , Gravidez/psicologia , Reprodutibilidade dos Testes
10.
Nat Genet ; 22(2): 192-5, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10369265

RESUMO

Deafness can result from a variety of gene defects. Some genes involved in the physiology of hearing encode membrane transporters that regulate the ionic composition of the fluid bathing the inner ear. The endolymph is an extracellular fluid with an atypical composition that resembles the intracellular milieu, high in K+ and low in Na+. Recent studies have emphasized the prominent role of K+ channels in endolymph secretion and mechanical transduction. Coupled electroneutral transport of Na+, K+ and Cl- is mediated by two isoforms of the Na-K-2Cl co-transporter: the absorptive isoform BSC1 (also called NKCC2, encoded by Slc12a1 in mouse) that is exclusively expressed in kidney; and BSC2/NKCC1 (encoded by Slc12a2 in mouse), the secretory isoform which has a wider pattern of expression including epithelia, muscle cells, neurons and red blood cells. These co-transporters share 57% homology at the amino acid level and are pharmacologically inhibited by loop diuretics. There is functional and histochemical evidence for the presence of the secretory isoform of the Na-K-2Cl co-transporter in gerbil, rat and rabbit inner ear. We disrupted mouse Slc12a2 and report here that Slc12a2-/- mice are deaf and exhibit classic shaker/waltzer behaviour, indicative of inner-ear defects. We localized the co-transporter to key secreting epithelia of the mouse inner ear and show that absence of functional co-transporter leads to structural damages in the inner ear consistent with a decrease in endolymph secretion.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cóclea/patologia , Surdez/genética , Transtornos dos Movimentos/genética , Órgão Espiral/patologia , Animais , Bumetanida/farmacologia , Surdez/patologia , Surdez/fisiopatologia , Eritrócitos/metabolismo , Células Ciliadas Auditivas Externas/patologia , Camundongos , Camundongos Knockout , Camundongos Mutantes Neurológicos , Atividade Motora , Transtornos dos Movimentos/patologia , Transtornos dos Movimentos/fisiopatologia , Potássio/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Coelhos , Ratos , Mapeamento por Restrição , Sódio/metabolismo , Simportadores de Cloreto de Sódio-Potássio
11.
J Invertebr Pathol ; 71(1): 48-52, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9446737

RESUMO

A species of Haplosporidium is described from 6 of 105 pearl oyster (Pinctada maxima) spat from a hatchery at Carnarvon in north Western Australia. Presporulation and sporulation stages occurred in the connective tissue surrounding the digestive gland and were common in mantle connective tissue, but only light to moderate infections were observed in the heart, gills, foot, and adductor muscle. No stages were observed in epithelia, and the gut and diverticulae remained intact. Ultrastructurally, sporoblasts were binucleate with the two nuclei either closely apposed to form a diplokaryon or separated, with the cytoplasm containing round to pyriform haplosporosomes. In spores the sporoplasm contained a basal, or sometimes equatorial, nucleus, dense ovoid vesicles that appeared to develop to ovoid haplosporosomes with an internal axehead-shaped membrane, and spherical haplosporosomes. Apparently senescent spores with a dense content were also present and they, and normal spores, were ornamented with filaments placing the parasite in the genus Haplosporidium. Copyright 1998 Academic Press. Copyright 1998 Academic Press

12.
Am J Physiol ; 273(4): C1267-77, 1997 10.
Artigo em Inglês | MEDLINE | ID: mdl-9357771

RESUMO

The Slc12a2 gene encodes a widely expressed bumetanide-sensitive Na+-K+-2Cl- cotransporter that participates in various functions such as Cl- secretion and cell volume regulation. We isolated and characterized 75 kilobases of the murine gene encoding the cotransporter. The cotransport protein is encoded by 27 exons. Ribonuclease protection assay and primer extension demonstrated tissue-specific transcription initiation sites located within 270 base pairs upstream of the start codon. Nucleotide sequence analysis of the proximal 5'-flanking region revealed the presence of a weak TATA box, multiple Sp1/GC consensus sites, and the consensus sequence of a putative transcriptional initiator. Transfection of luciferase reporter gene constructs in mouse inner medullary collecting duct (mIMCD-3) cells confirmed the location of the minimal promoter within a 120-base pair fragment upstream of the cDNA. We also report the identification of an alternatively spliced variant of the cotransporter, expressed primarily in brain. This new spliced variant lacks exon 21, which encodes a 16-amino acid peptide located in the COOH-terminal tail of the protein. The absence of this exon causes the loss of the single protein kinase A consensus site of the cotransport protein.


Assuntos
Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Animais , Sequência de Bases , Encéfalo/metabolismo , Proteínas de Transporte/química , Linhagem Celular , Clonagem Molecular , Sequência Consenso , Primers do DNA , Genes Reporter , Biblioteca Genômica , Medula Renal/metabolismo , Túbulos Renais Coletores/metabolismo , Células L , Luciferases/biossíntese , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/química , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Simportadores de Cloreto de Sódio-Potássio , Transcrição Gênica , Transfecção
13.
J Virol ; 70(12): 8502-7, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8970973

RESUMO

Most cell types are resistant to apoptosis induced by tumor necrosis factor (TNF) unless the cells are treated with a sensitizing agent. Inhibitors of transcription or translation act as sensitizing agents, as do adenoviruses lacking one or more resistance genes. We have reported recently that the activity of cytosolic phospholipase A2 (cPLA2) is necessary for the TNF-induced lysis of cells that are sensitized by inhibitors of transcription or translation (C. Voelkel-Johnson, T. E. Thorne, and S. M. Laster, J. Immunol. 156:201-207, 1996). In this report we have asked whether the lysis of cells infected by the adenovirus dl758 (which lacks the E3 14.7-kDa resistance gene product) also involves the activity of cPLA2. We report that a phosphorothioate-modified antisense oligonucleotide specific for cPLA2, but not the control oligonucleotide, inhibited the TNF-induced release of both [3H]arachidonic acid and 51Cr from infected cells. Arachidonyltrifluoromethyl ketone (AA COCF3), an inhibitor of cPLA2, also inhibited the release of 51Cr, and we found that the release of [3H]arachidonic acid was highly selective and was preferred over the release of [3H]palmitic acid. Taken together, these results suggest strongly that cPLA2 is indeed the phospholipase responsible for the release of [3H]arachidonic acid during the lysis of infected cells and that its activity is necessary for cell death. Finally, since arachidonic acid serves as the substrate for the synthesis of inflammatory lipids, our results suggest a possible link between the TNF-induced lysis of infected cells and inflammation. The E3 14.7-kDa resistance protein may, therefore, play two roles: preventing TNF-induced cell death and, as our results show, preventing the TNF-induced release of arachidonic acid.


Assuntos
Adenoviridae/metabolismo , Apoptose/fisiologia , Fosfolipases A/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Células 3T3 , Adenoviridae/patogenicidade , Animais , Ácido Araquidônico/metabolismo , Linhagem Celular , Citosol/enzimologia , Ácidos Graxos/metabolismo , Ligantes , Camundongos , Fosfolipases A2 , Trítio
14.
J Wildl Dis ; 32(3): 437-43, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8827669

RESUMO

A competitive-inhibition ELISA (CI-ELISA), based on a monoclonal antibody to an epitope conserved among malignant catarrhal fever virus (MCFV) strains of both wildebeest and sheep origin, was used to determine the prevalence of antibody to MCFV in selected domestic and wild ruminants, both free-ranging and captive, from the USA. We evaluated 2528 sera from 14 species between 1990 and 1995, including 80 pronghorn antelope (Antilocapra americana), 339 bighorn sheep (Ovis canadensis), 103 biston (Bison bison), 17 black-tailed deer (Odocoileus hemionus columbianus), 395 domestic cattle (Bos taurus), 291 domestic goats (Capra hircus), 680 domestic sheep (Ovis ammon), 323 elk (Cervus elaphus), 41 llamas (Lama glama), 21 mouflon sheep (Ovis musimon), 54 mountain goats (Oreamnos americanus), 101 mule deer (Odocoileus hemionus), 20 muskox (Ovibos moschatus), and 63 white-tailed deer (Odocoileus virginianus). A high seroprevalence (37 to 62%) was observed in domestic sheep, domestic goats, muskox, and some bighorn sheep populations. Seroprevalence in these species was generally age-related: a very low seroprevalence was present in these animals under one year of age. A low seroprevalence (2% to 13%) was found in clinically-susceptible species such as domestic cattle, deer, elk and bison, supporting the concept that significant numbers of non-lethal infections occur among clinically susceptible ruminants.


Assuntos
Anticorpos Antivirais/sangue , Herpesviridae/imunologia , Febre Catarral Maligna/epidemiologia , Ruminantes , Fatores Etários , Animais , Animais Domésticos , Animais Selvagens , Ligação Competitiva , Ensaio de Imunoadsorção Enzimática/veterinária , Febre Catarral Maligna/imunologia , Prevalência , Estados Unidos/epidemiologia
16.
J Immunol ; 156(1): 201-7, 1996 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-8598463

RESUMO

In this study, we have examined the relationship between the expression of the high molecular weight, cytosolic form of PLA2 (cPLA2) and ability of inhibitors of transcription or translation (ITT) to induce susceptibility to TNF. S Susceptibility to lysis was assayed by 51CR release, and the expression of cPLA2 was assayed by activity assay and by Western blot. The panel of cells that we examined included two murine cell lines, six human melanoma-derived cell lines, two samples of freshly explanted melanoma tumor tissue, and a culture of normal epidermal melanocytes. Our experiments revealed a near perfect correlation between the activity of cPLA2 per cell and susceptibility to TNF in the presence of either cycloheximide (CHI) or actinomycin D (r = 0.97). These results suggest that the activity of cPLA2 is both necessary and rate-limiting in this form of programmed cell death, conclusions that were confirmed in transfection experiments and in experiments with antisense oligonucleotides. Over-expression of cPLA2 in two melanoma-derived cell lines, WM793 and SK-MEL-131, led to enhanced susceptibility to TNF and CHI. Conversely, suppression of cPLA2 with antisense oligonucleotides dramatically decreased susceptibility to TNF and CHI in C3HA fibroblasts. These experiments also revealed a coupled, transformation-released change in the expression of cPLA2 and susceptibility to lysis. Normal melanocytes contained the lowest levels of cPLA2 and were completely resistant to sensitization with ITT. In contrast, all of the melanoma-derived cell lines and samples of melanoma tumor tissue we examined has higher levels of cPLA2 and could be killed, to some extent, by treatment with TNF and ITT.


Assuntos
Melanoma/enzimologia , Fosfolipases A/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Ácido Araquidônico/metabolismo , Sequência de Bases , Morte Celular/imunologia , Citosol/enzimologia , Ativação Enzimática/imunologia , Humanos , Melanoma/imunologia , Melanoma/metabolismo , Camundongos , Dados de Sequência Molecular , Oligonucleotídeos Antissenso , Fosfolipases A/análise , Fosfolipases A/efeitos dos fármacos , Fosfolipases A2 , Transfecção , Células Tumorais Cultivadas
17.
Mil Med ; 160(5): 217-9, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7659207

RESUMO

Aggressive pursuit of high-quality health care had guided the Health Service of the United States Army to establish a labor analgesia program within its hospitals. A dedicated Labor Epidural Service can be quite expensive, especially from the manpower standpoint. Therefore, the Anesthesia Service at Reynolds Army Community Hospital, Fort Sill, Oklahoma, implemented a program of intrathecal narcotic injection as an alternative to costly labor epidural analgesia. After reviewing a patient fact sheet, 150 laboring patients volunteered for labor intrathecal analgesia (LIA). Once active labor began, the patient received intrathecal morphine (0.25 mg) and fentanyl (25 micrograms). The pain level before and after the LIA was evaluated by the visual analog schedule method. At 2 weeks follow-up the intrathecal narcotic-assisted labor was subjectively reported by the patients. Ninety-four percent of the patients agreed that the LIA worked well and that they would do it again. LIA was found to be a well-accepted, cost-saving, very effective approach to labor analgesia.


Assuntos
Analgesia Obstétrica , Fentanila/administração & dosagem , Trabalho de Parto , Morfina/administração & dosagem , Dor/tratamento farmacológico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Humanos , Injeções Espinhais , Medição da Dor , Gravidez
18.
Plant Cell Rep ; 11(12): 601-4, 1992 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24213360

RESUMO

To improve turfgrasses using genetic engineering, we have developed a transformation system in turf-type tall fescue, one of the most important turfgrass species. Embryogenic cell cultures were established after callus induction from embryos of mature seed. The agarose-bead method with nurse cells was used to culture protoplasts and plants were regenerated from protoplasts of tall fescue cultured cells. To develop transgenic tall fescue plants, the hygromycin resistance gene and the ß-glucuronidase gene were introduced into the tall fescue protoplasts by electroporation. A high concentration (200 mg/l) of hygromycin was required to select transformed cells because of the high level of endogenous resistance to the antibiotic in tall fescue. Most of the transformed cells exhibited GUS activity and several plants were regenerated from these cells. The presence of introduced genes was confirmed by Southern blot hybridization of PCR amplified DNA from transgenic plants.

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