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1.
Int J Nurs Stud ; 107: 103566, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32380261

RESUMO

BACKGROUND: Sexual health is an integral part of overall health in older age. Research consistently reports that heterosexual and queer older people tend not to disclose sexual concerns and difficulties which increases the risks for sexually transmitted diseases. Older people are often absent from policies and information programmes and healthcare providers experience difficulties in initiating conversations around sexual health and history. OBJECTIVES: To identify what are the barriers that stop older people seeking sexual health advice and treatment. DESIGN AND METHOD: A scoping review methodology was employed. Published and unpublished literature was scoped through development of a research question, identification of potentially relevant studies, selection of relevant studies using an iterative team approach, charting data, collating, summarising and reporting findings, and considering the implications of study findings for further research. DATA SOURCES: Electronic databases searches were run to identify published and unpublished literature, including Medline, Embase, PsycINFO, CINAHL, ASSIA, Social Sciences, RCN and Cochrane Libraries. Additional studies were located through hand searching. RESULTS: Twelve studies from: the USA (n = 6); the UK (n = 3); Australia (n = 2); and one shared paper between New Zealand and UK met the inclusion criteria. Four barriers that stop older people seeking sexual health advice and treatment were identified, including (1) Cultural and societal views and beliefs toward sexual health; (2) Stigma, embarrassment and discrimination; (3) Lack of education and training of healthcare professionals; (4) Quality of relationship between patients and health professionals. CONCLUSION: Barriers to seeking and receiving advice and treatment for sexual health in later life clearly exist and are both related to cultural and social factors. Overall, the papers reviewed in this scoping review indicate that healthcare providers are reluctant to initiate conversations around sexual health or offer appropriate advice or clinical tests, and that older people tend to be hesitant to seek medical help. Later life age groups independently from their sexual orientation represent a hidden population and are absent from sexual health campaigns and government policies. Efforts need to be made by influential institutions and healthcare providers to recognise sexuality in older age and give older people the opportunity to open up regarding their sexual health and experiences.


Assuntos
Promoção da Saúde/métodos , Saúde Sexual/educação , Minorias Sexuais e de Gênero/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Geriatria/métodos , Promoção da Saúde/estatística & dados numéricos , Humanos , Masculino , Relações Profissional-Paciente , Saúde Sexual/estatística & dados numéricos , Minorias Sexuais e de Gênero/estatística & dados numéricos
2.
Mol Ecol ; 26(20): 5484-5499, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28833842

RESUMO

Range and niche expansion are commonly associated with transitions to asexuality, polyploidy and hybridity (allopolyploidy) in plants. The ability of asexual polyploids to colonize novel habitats may be due to widespread generalist clones, multiple ecologically specialized clones, or may be a neutral by-product of multiple, independent origins of asexual polyploids throughout the range. We have quantified niche size and divergence for hawthorns of the Pacific Northwest using data from herbarium vouchers with known cytotypes. We find that all polyploid niches diverge from that of the diploid range, and allopolyploids have the broadest niches. Allotetraploids have the largest niche and the widest geographic distribution. We then assessed the genetic mechanism of range expansion by surveying the ecological and geographic distribution of genotypes within each cytotype from sites in which fine-scale habitat assessments were completed. We find no isolation by either geographic or ecological distance in allopolyploids, suggesting high dispersal and colonization ability. In contrast, autotriploids and diploids show patterns of isolation by geographic distance. We also compared the geographic and ecological distributions of clonal genotypes with those of randomly drawn sites of the most widespread cytotype. We found that most clones are geographically widespread and occur in a variety of habitats. We interpret these findings to suggest that patterns of range and niche expansion in Pacific Northwest Hawthorns may stem from these widespread, ecologically generalist clones of hybrid origin.


Assuntos
Crataegus/genética , Ecossistema , Genética Populacional , Poliploidia , Crataegus/fisiologia , DNA de Plantas/genética , Diploide , Variação Genética , Genótipo , Geografia , Repetições de Microssatélites , Noroeste dos Estados Unidos , Dispersão Vegetal , Reprodução Assexuada
3.
J Psychiatr Ment Health Nurs ; 22(6): 413-22, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26122924

RESUMO

ACCESSIBLE SUMMARY: Little is known about how the prison environment may impact upon the mental health of adult prisoners. This paper highlights that prisoners perceive that the prison environment has a negative influence upon their mental health. However, a small number regarded prison as a place of respite, which afforded structure and an opportunity to access health services. There is a need for more research in this area specifically relating to the impact the prison climate may have upon those from black and minority ethic groups. Nurses must recognize the aspects of the prison environment that may impact upon the mental health of prisoners and demonstrate innovation and imagination in their application of interventions. ABSTRACT: Little is known regarding how the prison environment may affect the mental health of adult prisoners. Consequently, there is a need to investigate how this setting may exacerbate mental distress among this community. This literature review explores how the prison climate influences the mental health of adult prisoners. A thematic synthesis approach was used to elicit data relating to the aspects of the prison climate, which influence the mental health of prisoners. Four primary themes emerged from the synthesis: social, emotional, organizational and physical aspects. Prisoners perceive the prison climate to have a negative influence upon their mental health. However, perceived positively, prison was regarded as a place of respite, which afforded structure and an opportunity to access health services. There is limited research available specifically exploring the potential impact of the prison climate upon those from black and ethnic minorities groups. Nurses must recognize the aspects of the prison environment that may impact upon the mental health of prisoners and demonstrate innovation and imagination in their application of interventions. Additionally nurses need to take an active role in influencing and structuring the political agenda, which governs the clinical setting.


Assuntos
Saúde Mental/normas , Prisioneiros/psicologia , Prisões/normas , Humanos
4.
Ann Bot ; 114(2): 253-69, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24984714

RESUMO

BACKGROUND AND AIMS: The taxonomic complexity of Crataegus (hawthorn; Rosaceae, Maleae), especially in North America, has been attributed by some to hybridization in combination with gametophytic apomixis and polyploidization, whereas others have considered the roles of hybridization and apomixis to be minimal. Study of the chemical composition and therapeutic value of hawthorn extracts requires reproducible differentiation of entities that may be difficult to distinguish by morphology alone. This study sought to address this by using the nuclear ribosomal spacer region ITS2 as a supplementary DNA barcode; however, a lack of success prompted an investigation to discover why this locus gave unsatisfactory results. METHODS: ITS2 was extensively cloned so as to document inter- and intraindividual variation in this locus, using hawthorns of western North America where the genus Crataegus is represented by only two widely divergent groups, the red-fruited section Coccineae and the black-fruited section Douglasia. Additional sequence data from selected loci on the plastid genome were obtained to enhance further the interpretation of the ITS2 results. KEY RESULTS: In the ITS2 gene tree, ribotypes from western North American hawthorns are found in two clades. Ribotypes from diploid members of section Douglasia occur in one clade (with representatives of the east-Asian section Sanguineae). The other clade comprises those from diploid and polyploid members of section Coccineae. Both clades contribute ribotypes to polyploid Douglasia. Data from four plastid-derived intergenic spacers demonstrate the maternal parentage of these allopolyploids. CONCLUSIONS: Repeated hybridization between species of section Douglasia and western North American members of section Coccineae involving the fertilization of unreduced female gametes explains the observed distribution of ribotypes and accounts for the phenetic intermediacy of many members of section Douglasia.


Assuntos
Evolução Biológica , Núcleo Celular/genética , Crataegus/genética , DNA Espaçador Ribossômico/genética , Frutas/genética , Plastídeos/genética , Sequência de Bases , Variação Genética , Hibridização Genética , Modelos Biológicos , América do Norte , Conformação de Ácido Nucleico , Filogenia , Poliploidia , Especificidade da Espécie
5.
Br J Cancer ; 107(2): 388-99, 2012 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-22644296

RESUMO

BACKGROUND: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues. METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody. RESULTS: A novel sequence was identified within the 3'-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ(-PrC)) independent of conventional PKC-ζ(-a). The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium. INTERPRETATION: Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-ß and atypical PKC-ι within PKC-ζ(-PrC) provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.


Assuntos
Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/genética , Proteína Quinase C/biossíntese , Proteína Quinase C/genética , Sequência de Aminoácidos , Sequência de Bases , Biomarcadores Tumorais/metabolismo , Domínio Catalítico , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Variação Genética , Humanos , Masculino , Dados de Sequência Molecular , Fenótipo , Neoplasias da Próstata/metabolismo , Proteína Quinase C/metabolismo , Splicing de RNA , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transcrição Gênica , Transcriptoma/genética
7.
J Plant Res ; 122(3): 253-68, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19184674

RESUMO

The taxonomic integrity of Vaccinium section Bracteata sensu Sleumer was assessed using a variety of numerical measures on a data matrix created from 46 OTUs scored for 65 descriptors. These analyses supported a much restricted ambit for section Bracteata and the concomitant resurrection of section Nesococcus and section Euepigynium, a more cosmopolitan interpretation for section Eococcus and section Pyxothamnus as well as a new taxon, Vaccinium section Baccula-nigra Kloet, sect. nov. to accommodate V. fragile Franch. and its conspecifics. A key to all the sections as well as a brief description for each section is also provided.


Assuntos
Ecossistema , Geografia , Metamorfose Biológica , Vaccinium/classificação , Análise por Conglomerados , Flores/fisiologia , Frutas/fisiologia , Análise de Componente Principal
8.
Mol Cell Neurosci ; 30(4): 523-37, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16202621

RESUMO

Activation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha. A VPAC2 receptor agonist enhanced p38 phosphorylation and caused behavioral reflex sensitization in naïve animals that could be blocked by co-administration of p38 inhibitor. Conversely, an NK2 receptor agonist activated p42/44 and caused behavioral sensitization that could be prevented by co-administration of p42/44 inhibitor. Thus, spinal p38 and p42/44 MAP kinases are activated in neuropathic pain states by mechanisms involving VPAC2, NK2, NMDA receptors and glial cytokine production.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Neuroglia/metabolismo , Doenças do Sistema Nervoso Periférico/metabolismo , Células do Corno Posterior/metabolismo , Receptores da Neurocinina-2/metabolismo , Receptores Tipo II de Peptídeo Intestinal Vasoativo/metabolismo , Animais , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Mediadores da Inflamação/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Proteína Quinase 1 Ativada por Mitógeno/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Neuroglia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismos dos Nervos Periféricos , Nervos Periféricos/metabolismo , Nervos Periféricos/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Fosforilação/efeitos dos fármacos , Estimulação Física , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores da Neurocinina-2/efeitos dos fármacos , Receptores Tipo II de Peptídeo Intestinal Vasoativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismo , Xantinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Antimicrob Agents Chemother ; 46(1): 24-30, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11751106

RESUMO

Staphylococci that acquire the mecA gene are usually resistant to beta-lactam antibiotics (methicillin or oxacillin resistance). mecA encodes a penicillin-binding protein (PBP 2a) that has a reduced affinity for beta-lactams. In some isolates with methicillin or oxacillin resistance, only a small proportion (< or =0.1%) of the population expresses resistance to > or =10 microg of oxacillin per ml (heterotypic resistance [HeR]), while in other isolates most of the population expresses resistance (homotypic resistance [HoR]). In the present study, growth of Staphylococcus aureus or Staphylococcus epidermidis strains with HeR in concentrations of oxacillin (0.3 to 0.7 microg/ml) that produced a fall or a lag in optical density converted the strains from the HeR to the HoR phenotype. The conversion from the HeR to the HoR phenotype appeared to be due to the selection of a highly resistant mutant population, as determined by fluctuation analysis and the failure of populations with HoR to revert to HeR after 60 generations of growth in antibiotic-free media. The frequencies of conversion were as high as 10(-3) to 10(-2). Conversion to HoR required an intact mecA gene and an increase in the level of mecA transcription since no highly resistant subpopulation could be selected after growth in oxacillin when mecA transcription was constitutively repressed or when mecA had been inactivated. In addition, in both S. epidermidis and S. aureus the level of resistance to vancomycin, which also acts directly on the staphylococcal cell wall, was greater among convertants with HoR than their isogenic parents. The conversion of a population from HeR to HoR involves the selection of a mutation(s) that occurs at a high frequency and most likely requires abundant PBP 2a.


Assuntos
Proteínas de Bactérias , Hexosiltransferases , Oxacilina/farmacologia , Penicilinas/farmacologia , Peptidil Transferases , Staphylococcus/efeitos dos fármacos , Antibacterianos/farmacologia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Resistência a Medicamentos/genética , Macrolídeos , Muramilpentapeptídeo Carboxipeptidase/genética , Muramilpentapeptídeo Carboxipeptidase/metabolismo , Proteínas de Ligação às Penicilinas , Fenótipo , Staphylococcus/genética , Vancomicina/farmacologia
10.
J Vasc Surg ; 34(3): 548-54, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11533610

RESUMO

PURPOSE: Endothelin-1 (ET-1) has been implicated in a variety of vascular pathologic conditions, although there is considerable controversy as to whether such effects are mediated by the ET-(A) or ET-(B) receptor. This study investigated whether inhibition of big ET-1 processing by inhibition of endothelin-converting enzyme (ECE) could, therefore, offer an alternative therapeutic strategy in the prevention of vein graft intimal hyperplasia. METHODS: Human saphenous vein (3 equal segments from 10 patients) were maintained in organ culture for 14 days with either 50 micromol/L CGS 26303 (a dual ECE/neutral endopeptidase [NEP] inhibitor), 50 micromol/L CGS 24592 (a selective NEP inhibitor), or vehicle (control). They were then processed for immunostaining and neointimal thickness measurements, and conditioned media was collected for enzyme-linked immunosorbent assay analysis. RESULTS: Neointimal thickness in the ECE/NEP-inhibited veins did not differ significantly from that of control segments. However, there was a highly significant augmentation in the NEP-inhibited segments, consistent with an inhibition of ET-1 degradation (median difference, 16.8; 95% CI, -23.5, -10.4; P =.002, Wilcoxon). ECE immunostaining was reduced in the ECE/NEP-inhibited veins, although ET-1 staining was also present. ET-1 expression was intense in the thickened neointimas of NEP-inhibited veins, which also showed significant ECE staining. Elevated levels of big ET-1 were measured in the ECE/NEP-inhibited veins, consistent with reduced ECE activity. However, mature ET-1 was still detectable in these segments. CONCLUSION: There is a requirement for potent and selective inhibitors of ECE to evaluate fully the potential therapeutic benefits of blocking ET-1 biosynthesis. The use of dual inhibitors complicates the interpretation of results, because the observed response is likely to be a combination of both ECE and NEP inhibition.


Assuntos
Ácido Aspártico Endopeptidases/antagonistas & inibidores , Neprilisina/antagonistas & inibidores , Veia Safena/crescimento & desenvolvimento , Túnica Íntima/crescimento & desenvolvimento , Enzimas Conversoras de Endotelina , Humanos , Metaloendopeptidases , Técnicas de Cultura de Órgãos
11.
Science ; 293(5529): 498-506, 2001 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-11463916

RESUMO

The 2,160,837-base pair genome sequence of an isolate of Streptococcus pneumoniae, a Gram-positive pathogen that causes pneumonia, bacteremia, meningitis, and otitis media, contains 2236 predicted coding regions; of these, 1440 (64%) were assigned a biological role. Approximately 5% of the genome is composed of insertion sequences that may contribute to genome rearrangements through uptake of foreign DNA. Extracellular enzyme systems for the metabolism of polysaccharides and hexosamines provide a substantial source of carbon and nitrogen for S. pneumoniae and also damage host tissues and facilitate colonization. A motif identified within the signal peptide of proteins is potentially involved in targeting these proteins to the cell surface of low-guanine/cytosine (GC) Gram-positive species. Several surface-exposed proteins that may serve as potential vaccine candidates were identified. Comparative genome hybridization with DNA arrays revealed strain differences in S. pneumoniae that could contribute to differences in virulence and antigenicity.


Assuntos
Genoma Bacteriano , Análise de Sequência de DNA , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidade , Antígenos de Bactérias , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Vacinas Bacterianas , Composição de Bases , Metabolismo dos Carboidratos , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cromossomos Bacterianos/genética , Biologia Computacional , Elementos de DNA Transponíveis , DNA Bacteriano/química , DNA Bacteriano/genética , Duplicação Gênica , Genes Bacterianos , Hexosaminas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Recombinação Genética , Sequências Repetitivas de Ácido Nucleico , Especificidade da Espécie , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/metabolismo , Virulência , Óperon de RNAr
12.
Neurosci Res ; 39(4): 385-90, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11274737

RESUMO

Some opioid-resistant pain conditions can be alleviated by voltage-dependent Na(+) channel blockers such as lamotrigine. The mu-opioid-receptor agonist morphine can modulate cation entry into cells to affect overall cellular excitability, an effect which can in turn be endogenously antagonised by the neuropeptide cholecystokinin (CCK). However, lamotrigine may also modulate cellular excitability by non-specifically blocking voltage-dependent ion channels. We have looked for interactions of lamotrigine with the opioid/CCK pathway within the spinal dorsal horn, to rule out the possibility that lamotrigine may attenuate nociceptive responses via actions on this pathway. Both lamotrigine and the mu-opioid agonist DAMGO inhibited mustard oil-evoked cell firing by approximately 50% compared with control levels. Co-application of CCK8S reversed DAMGO-, but not lamotrigine-induced inhibition of cell firing and this reversal was prevented with the selective CCK(B) receptor antagonist PD 135158. Although lamotrigine inhibited both brush- and cold-evoked cell firing in neuropathic animals, lamotrigine inhibition of mustard oil-evoked cell firing in the same animals was not significantly greater than that observed in controls. These results suggest that the antinociceptive properties of lamotrigine within the spinal dorsal horn are unlikely to be mediated via interactions with the opioid/CCK pathway.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Vias Neurais/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Peptídeos Opioides/metabolismo , Dor/tratamento farmacológico , Células do Corno Posterior/efeitos dos fármacos , Triazinas/farmacologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Analgésicos Opioides/farmacologia , Animais , Ansiolíticos/farmacologia , Colecistocinina/metabolismo , Ala(2)-MePhe(4)-Gly(5)-Encefalina/farmacologia , Indóis/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Lamotrigina , Masculino , Meglumina/análogos & derivados , Meglumina/farmacologia , Mostardeira , Vias Neurais/citologia , Vias Neurais/metabolismo , Nociceptores/citologia , Nociceptores/metabolismo , Dor/metabolismo , Dor/fisiopatologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Extratos Vegetais/farmacologia , Óleos de Plantas , Células do Corno Posterior/citologia , Células do Corno Posterior/metabolismo , Ratos , Ratos Wistar , Sincalida/farmacologia
13.
Nucleic Acids Res ; 29(1): 123-5, 2001 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11125067

RESUMO

One challenge presented by large-scale genome sequencing efforts is effective display of uniform information to the scientific community. The Comprehensive Microbial Resource (CMR) contains robust annotation of all complete microbial genomes and allows for a wide variety of data retrievals. The bacterial information has been placed on the Web at http://www.tigr.org/CMR for retrieval using standard web browsing technology. Retrievals can be based on protein properties such as molecular weight or hydrophobicity, GC-content, functional role assignments and taxonomy. The CMR also has special web-based tools to allow data mining using pre-run homology searches, whole genome dot-plots, batch downloading and traversal across genomes using a variety of datatypes.


Assuntos
Bactérias/genética , Bases de Dados Factuais , Genes Bacterianos/genética , Genoma Bacteriano , Serviços de Informação , Internet
14.
Br J Surg ; 87(10): 1409-13, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11044168

RESUMO

BACKGROUND: The aim was to assess the role of plasma Big Endothelin (ET) 1 levels as a marker of disease presence and stage in colorectal adenocarcinoma. METHODS: Big ET-1 was measured in the plasma of 37 patients with colorectal cancer. Preoperative systemic plasma levels of Big ET-1 in patients with cancer were compared with levels in 20 age- and sex-matched controls. Portal plasma samples were collected at operation in addition to peripheral venous samples. Immunohistochemical staining for Big ET-1 was performed on a selection of primary tumour specimens and liver metastases. RESULTS: Median (range) preoperative systemic plasma levels of Big ET-1 were significantly higher in patients with cancer than in controls (1.0 (0.3-9.7) versus 0.2 (0.0-6.0) fmol/ml; P = 0.0001). Intraoperative portal plasma levels of Big ET-1 were significantly higher in patients with Dukes' 'D' disease than in patients with Dukes' A, B and C disease (2.1 (1.4-10.0) versus 1.2 (0.3-6.6) fmol/ml; P = 0. 01). Similarly, systemic plasma levels were significantly higher in patients with Dukes' 'D' disease than in those with localized disease (1.9 (1.2-9.7) versus 1.2 (0.2-8.3) fmol/ml; P = 0.01). The presence of microvascular invasion in the tumour specimens was associated with a significantly raised portal plasma level of Big ET-1 (1.6 (1.5-2.1) versus 1.1 (0.8-1.3) fmol/ml; P = 0.04). Immunohistochemistry localized Big ET-1 to the cancer epithelial cells. CONCLUSION: The plasma level of Big ET-1 is significantly raised in patients with colorectal cancer. Patients with liver metastases have significantly higher levels than those with localized disease.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/diagnóstico , Endotelinas/sangue , Precursores de Proteínas/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Endotelina-1 , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
16.
Antimicrob Agents Chemother ; 44(6): 1616-23, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10817718

RESUMO

The MICs for many oxacillin-resistant (OR) Staphylococcus epidermidis (ORSE) strains are below the Staphylococcus aureus methicillin or oxacillin resistance breakpoint. The difficulty detecting the OR phenotype in S. epidermidis may be due to extreme heterotypy in resistance expression and/or transcriptional repression of mecA, the OR gene, by MecI. To determine the role of these factors in the phenotypic expression of ORSE, 17 geographically diverse mecI(+) ORSE isolates representing 14 distinct pulsed-field gel electrophoresis pulse types (>3 band differences) were investigated. Thirteen of the 14 types contained mecI and mecA promoter-operator sequences known to be associated with maximal mecA repression, and in all isolates, mecA transcription was repressed. All 17 were heterotypic in their resistance expression. Oxacillin MICs ranged from 1 to 128 microg/ml and increased for 16 of 17 isolates after beta-lactam induction. Allelic replacement inactivation of mecI in three isolates similarly resulted in a four- to sevenfold increase in MIC. In the two of these three isolates producing beta-lactamase, mecA transcription was regulated by both mecI and beta-lactamase regulatory sequences. Heterotypic expression of resistance in these three isolates was unaffected by either beta-lactam induction or mecI inactivation. However, prolonged incubation in concentrations of oxacillin just sufficient to produce a lag in growth (0.5 to 1.0 microg/ml) converted the population resistance expression from heterotypic to homotypic. Homotypic conversion could also be demonstrated in microtiter wells during MIC determinations in one isolate for which the MIC was high. We conclude that the phenotypic expression of S. epidermidis OR in broth can be affected both by mecA transcriptional regulation and by subpopulation resistance expression.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Transporte/genética , Genes Bacterianos , Hexosiltransferases , Muramilpentapeptídeo Carboxipeptidase/genética , Oxacilina/farmacologia , Resistência às Penicilinas/genética , Penicilinas/farmacologia , Peptidil Transferases , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Ligação às Penicilinas , Transcrição Gênica
17.
Mol Phylogenet Evol ; 17(3): 388-400, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11133193

RESUMO

We sampled the 5' end of the granule-bound starch synthase gene (GBSSI or waxy) in Rosaceae, sequencing 108 clones from 18 species in 14 genera representing all four subfamilies (Amygdaloideae, Maloideae, Rosoideae, and Spiraeoideae), as well as four clones from Rhamnus catharticus (Rhamnaceae). This is the first phylogenetic study to use the 5' portion of this nuclear gene. Parsimony and maximum-likelihood analyses of 941 bases from seven complete and two partial exons demonstrate the presence of two loci (GBSSI-1 and GBSSI-2) in the Rosaceae. Southern hybridization analyses with locus-specific probes confirm that all four Rosaceae subfamilies have at least two GBSSI loci, even though only one locus has been reported in all previously studied diploid flowering plants. Phylogenetic analyses also identify four clades representing four loci in the Maloideae. Phylogenetic relationships inferred from GBSSI sequences are largely compatible with those from chloroplast (cpDNA: ndhF, rbcL) and nuclear ribosomal internal transcribed spacer (nrITS) DNA. Large clades are marked by significant intron variation: a long first intron plus no sixth intron in Maloideae GBSSI-1, a long fourth intron in Rosoideae GBSSI-1, and a GT to GC mutation in the 5' splice site of the fourth intron in all GBSSI-2 sequences. Our data do not support the long-held hypothesis that Maloideae originated from an ancient hybridization between amygdaloid and spiraeoid ancestors. Instead, Spiraeoideae genera (Kageneckia and Vauquelinia) are their closest relatives in all four GBSSI clades.


Assuntos
Grânulos Citoplasmáticos/enzimologia , Evolução Molecular , Magnoliopsida/enzimologia , Magnoliopsida/genética , Filogenia , Sintase do Amido/genética , Sequência de Bases , Southern Blotting , Classificação , Clonagem Molecular , Biologia Computacional , Grânulos Citoplasmáticos/metabolismo , Primers do DNA , Dosagem de Genes , Variação Genética/genética , Magnoliopsida/classificação , Dados de Sequência Molecular , Alinhamento de Sequência
18.
Trends Pharmacol Sci ; 20(8): 324-9, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10431211

RESUMO

Neuropathic pain arising from direct trauma to, or compression injury of, peripheral nerves is a common clinical problem. It is characterized by the development of abnormal pain states (spontaneous pain, hyperalgesia, allodynia), which can persist long after the initial injury has resolved. The underlying mechanisms are poorly understood and, as a consequence, treatment is often unsatisfactory. Some of the main contributing factors are thought to be the morphological and phenotypic changes that occur centrally, including alterations in the expression of neurotransmitters and their associated receptors, both in the dorsal root ganglia and in the spinal dorsal horn. This article focuses on the functional role of the two structurally related peptides VIP and PACAP within the spinal cord, and their possible contribution to the altered transmission of sensory information in neuropathic conditions.


Assuntos
Neuropeptídeos/fisiologia , Dor/fisiopatologia , Traumatismos dos Nervos Periféricos , Sistemas do Segundo Mensageiro/fisiologia , Medula Espinal/química , Peptídeo Intestinal Vasoativo/fisiologia , Animais , Gânglios Espinais/química , Dor/etiologia , Nervos Periféricos/patologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores do Hormônio Hipofisário/fisiologia , Receptores de Peptídeo Intestinal Vasoativo/fisiologia , Receptores Tipo II de Peptídeo Intestinal Vasoativo , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo , Sistemas do Segundo Mensageiro/efeitos dos fármacos
19.
Anal Chem ; 71(11): 2192-8, 1999 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10366892

RESUMO

We report a new approach to designing an artificial nose based on high-density optical arrays that directly incorporate a number of structural and operational features of the olfactory system. The arrays are comprised of thousands of microsphere (bead) sensors, each belonging to a discrete class, randomly dispersed across the face of an etched optical imaging fiber. Beads are recognized and classified after array assembly by their unique, "self-encoded" response pattern to a selected vapor pulse. The high degree of redundancy built into the array parallels that found in nature and affords new opportunities for chemical-sensor signal amplification. Since each bead is independently addressable through its own light channel, it is possible to combine responses from same-type beads randomly distributed throughout the array in a manner reminiscent of the sensory-neuron convergence observed in the mammalian olfactory system. Signal-to-noise improvements of approximately n1/2 have been achieved using this method.


Assuntos
Técnicas Biossensoriais , Tecnologia de Fibra Óptica , Microesferas , Odorantes/análise , Órgãos Artificiais , Processamento de Imagem Assistida por Computador/métodos , Modelos Biológicos , Nariz/fisiologia , Bulbo Olfatório/fisiologia
20.
Neuropharmacology ; 38(1): 167-80, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10193908

RESUMO

Peripheral nerve damage often results in the development of chronic pain states, resistant to classical analgesics. Since vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) are up-regulated in dorsal root ganglion cells following peripheral nerve injury, we investigated the expression and influence of VPAC1, VPAC2 and PAC1 receptors in rat spinal dorsal horn following a chronic constriction injury (CCI). Electrophysiological studies revealed that selective antagonists of VPAC1, VPAC2 and PAC1 receptors inhibit mustard oil-, but not brush-induced activity of dorsal horn neurones in CCI animals, while cold-induced neuronal activity was attenuated by VPAC1 and PAC1, but not VPAC2 receptor antagonists. Ionophoresis of selective agonists for the receptor subtypes revealed that the VPAC2 receptor agonist excited twice as many cells in CCI compared to normal animals, while the number of cells excited by the VPAC1 receptor agonist decreased and responses to PACAP-38 remained unchanged. In situ hybridisation histochemistry (ISHH) confirmed an increase in the expression of VPAC2 receptor mRNA within the ipsilateral dorsal horn following neuropathy, while VPAC1 receptor mRNA was seen to decrease and that for PAC1 receptors remained unchanged. These data indicate that VIP/PACAP receptors may be important regulatory factors in neuropathic pain states.


Assuntos
Neuralgia/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Receptores do Hormônio Hipofisário/fisiologia , Receptores de Peptídeo Intestinal Vasoativo/fisiologia , Sensação/fisiologia , Medula Espinal/fisiopatologia , Animais , Comportamento Animal/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Histocitoquímica/métodos , Hibridização In Situ , Masculino , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Doenças do Sistema Nervoso Periférico/etiologia , Ratos , Ratos Wistar , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Receptores do Hormônio Hipofisário/agonistas , Receptores de Peptídeo Intestinal Vasoativo/agonistas , Receptores Tipo II de Peptídeo Intestinal Vasoativo , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo , Medula Espinal/efeitos dos fármacos , Estresse Mecânico , Regulação para Cima
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