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Disused Sealed Radioactive Sources (DSRS) borehole disposal is an innovative concept recommended by international atomic energy agency (IAEA) to improve the safety and security of the management end point for these sources. A green application of Palm Oil Fuel Ash (POFA) as a supplementary material for cementitious backfill barrier in DSRS borehole disposal facility is proposed. Samples with up to 50% POFA replacement complied with the mechanical and hydraulic performance requirements for backfill barriers in retrievable radioactive waste disposal facilities. The structures of one year old OPC and optimum OPC-POFA cement backfills were evaluated using FESEM, XRD, EDXRF, BET, and TGA and their 226 Ra confinement performances were assessed. 30% POFA replacement improved the geochemical conditions by reducing competitive Ca2+ release into the disposal environment. It enhanced 226Ra confinement performance independently on the amount of water intrusion or releases below 2% of 1 Ci source. The improved performance is attributed to the higher fraction of active sites of OPC-POFA backfill compared to that of OPC backfill. 226Ra sorption onto C-S-H is irreversible, spontaneous, endothermic, and independent on the degree of the surface filling. The provided experimental data and theoretical analysis proved the feasibility of this green use of POFA in reducing the radiological hazard of 226Ra.
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Resíduos Radioativos , Eliminação de Resíduos , Materiais de Construção , Óleo de Palmeira , Resíduos Radioativos/análise , ÁguaRESUMO
Magnetic skyrmions are nanoscale topological spin structures offering great promise for next-generation information storage technologies. The recent discovery of sub-100-nm room-temperature (RT) skyrmions in several multilayer films has triggered vigorous efforts to modulate their physical properties for their use in devices. Here we present a tunable RT skyrmion platform based on multilayer stacks of Ir/Fe/Co/Pt, which we study using X-ray microscopy, magnetic force microscopy and Hall transport techniques. By varying the ferromagnetic layer composition, we can tailor the magnetic interactions governing skyrmion properties, thereby tuning their thermodynamic stability parameter by an order of magnitude. The skyrmions exhibit a smooth crossover between isolated (metastable) and disordered lattice configurations across samples, while their size and density can be tuned by factors of two and ten, respectively. We thus establish a platform for investigating functional sub-50-nm RT skyrmions, pointing towards the development of skyrmion-based memory devices.
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Craniosynostosis is a premature pathologic fusion of one or more cranial vault sutures leading to abnormally-shaped skull. It can occur in isolated event (non-syndromic), or it can occur in conjunction with other anomalies in welldefined patterns (syndromic). The diagnosis rests on clinical examination and confirmation is generally on the computed tomography scan. The need for surgery is both for cosmetic and functional reasons. Here we describe a case of nonsyndromic craniosynostosis that was treated with frontal orbital advancement (FOA). The potential benefits of FOA need to be carefully weighed against the potential complications when deciding for any surgical intervention.
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Craniossinostoses/cirurgia , Órbita/cirurgia , Feminino , Humanos , LactenteRESUMO
No abstract available.
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Most studies comparing medial pivot to the posterior stabilised (PS) systems sacrifice the PCL. It is unknown whether retaining the PCL in the Medial Congruent (MC) system may provide further benefit compared to the more commonly used PS system. A retrospective review of a single-surgeon's registry data comparing 44 PS and 26 MC with PCL retained (MC-PCLR) TKAs was performed. Both groups had similar baseline demographics. The PS and MC-PCLR groups had similar pre-operative range of motion (ROM) (PS:104º ± 20º vs. MC-PCLR: 101º ± 19º, p = 0.70), Oxford Knee Score (OKS) (PS: 27 ± 6 vs. MC-PCLR: 26 ± 7, p = 0.62), and Knee Society Scoring System (KS) Function Score (KS-FS) (PS: 52 ± 24 vs. MC-PCLR: 56 ± 23, p = 0.49). The pre-operative KS Knee Score (KS-KS) was significantly lower in the PS group (PS: 44 ± 14 vs. MC-PLR: 53 ± 18, p < 0.05). At 12-months post-operation, there was significant improvement in all parameters (p < 0.01). Both groups had similar ROM (PS: 115º ± 13º vs. MC-PCLR: 114º ± 10º, p = 0.98), OKS (PS: 41 ± 5 vs. MC-PCLR: 40 ± 4, p = 0.50), KS-FS (PS: 74 ± 22 vs. MC-PCLR: 77 ± 16, p = 0.78), and KS-KS (PS: 89 ± 10 vs. MC-PCLR: 89 ± 10, p = 0.89). The PS group had significant improvement in all parameters from preoperation to 3-month postoperation (p < 0.05), but not from 3-month to 1-year postoperation (p ≥ 0.05). The MC-PCLR group continued to have significant improvement from 3-month to 1-year postoperation (p < 0.05). Preserving the PCL when using MC may paradoxically cause an undesired additional restrain that slows the recovery process of the patients after TKA. Compared to MC-PCLR, a PS TKA may expect significantly faster improvement at 3 months post operation, although they will achieve similar outcomes at 1-year post operation.
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Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Ligamento Cruzado Posterior , Humanos , Ligamento Cruzado Posterior/cirurgia , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Amplitude de Movimento ArticularRESUMO
OBJECTIVE: Depression among patients with vascular dementia is frequently overlooked and potentially causes significant morbidity. There is limited data in Malaysia on the subject and this study was conducted to determine the prevalence of depression in vascular dementia (VaD) in UKMMC. METHODS: This was a cross-sectional study involving diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria and who had a mini mental state examination (MMSE) score of less than 26. All patients were interviewed, examined clinically and their previous brain computer tomography (CT) were reviewed. The prevalence of depression was determined using the Cornell scale of depression. RESULTS: A total of 76 patients were recruited with a mean age of 70.5 ± 9.5 years. The median duration of illness was 2.0 (1.0-4.8) years. The prevalence of depression in the study population was 31.6%. The patients with depression had a significant older mean age (74.5±8.7 years old) compared to those without depression (68.6±9.4 years old). Patients with large artery stroke of less than 3 years had significant higher frequency of depression (53.6%) compared to patients with small artery stroke (23.8%) and patients with right sided large artery stroke had significantly higher frequency of depression compared to left (70% vs. 44.4%). Median MMSE score (17.0) for depressed patients was significantly lower compared with median MMSE score (22.5) for non depressed patients. Median Barthel Index (30.0) for depressed patients was significantly lower compared with median Barthel score for non depressed patients. CONCLUSIONS: Depression was prevalent among post stroke patients with VaD in UKMMC particularly for patients with older age, large artery stroke, right sided large artery stroke, low MMSE score and low Barthel Index. Early recognition of high risk patients is important in the holistic management of patients to prevent significant morbidity arising from depression.
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Demência Vascular , Depressão , Estudos Transversais , Depressão/diagnóstico , Humanos , Malásia , Prevalência , Acidente Vascular Cerebral/epidemiologiaRESUMO
The Raman spectra of Si nanocrystals are studied as a function of nanocrystal diameter using pseudopotential density functional theory and the Placzek approximation. Our calculations reproduce the redshift and broadening of the optical Raman peak with decreasing nanocrystal size, and calculated peak frequencies show good agreement with experimental values. We also find that a surface induced softening of vibrational modes is largely responsible for the Raman redshift, with relaxation of momentum conservation playing only a minor role.
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Manipulation of proteins by chemical modification is a powerful way to decipher their function. However, most ribosome-dependent and semi-synthetic methods have limitations in the number and type of modifications that can be introduced, especially in live cells. Here, we present an approach to incorporate single or multiple post-translational modifications or non-canonical amino acids into proteins expressed in eukaryotic cells. We insert synthetic peptides into GFP, NaV1.5 and P2X2 receptors via tandem protein trans-splicing using two orthogonal split intein pairs and validate our approach by investigating protein function. We anticipate the approach will overcome some drawbacks of existing protein enigineering methods.
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Peptídeos/metabolismo , Processamento de Proteína , Trans-Splicing , Animais , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Peptídeos/química , Biossíntese de Proteínas , Domínios Proteicos , Proteínas Recombinantes/metabolismo , Xenopus laevisRESUMO
In a large group of patients with the clinical phenotype of familial hypercholesterolemia, such as elevated low-density lipoprotein (LDL) cholesterol and premature atherosclerosis, but without functional mutations in the genes coding for the LDL receptor and apolipoprotein B, we examined the effect of 128 seemingly neutral exonic and intronic DNA variants, discovered by routine sequencing of these genes. Two variants, G186G and R385R, were found to be associated with altered splicing. The nucleotide change leading to G186G resulted in the generation of new 3'-splice donor site in exon 4 and R385R was associated with a new 5'-splice acceptor site in exon 9 of the LDL receptor gene. Splicing of these alternate splice sites leads to an in-frame 75-base pair deletion in a stable mRNA of exon 4 in case of G186G and R385R resulted in a 31-base pair frame-shift deletion in exon 9 and non-sense-mediated mRNA decay.
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Éxons/genética , Hipercolesterolemia/genética , Mutação , Splicing de RNA , Receptores de LDL/genética , Adolescente , Adulto , Idoso , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Infliximab is an anti-tumour necrosis factor monoclonal antibody, which significantly improves pain, stiffness and functional disability outcomes in patients with active ankylosing spondylitis. There are limited data available on the efficacy of this treatment for the subgroup with established spinal ankylosis. AIM: To compare the treatment response of infliximab in active severe ankylosing spondylitis for patients with and without radiographic evidence of spinal ankylosis in the clinical practice setting. METHODS: Twenty-seven patients with mean Bath Ankylosing Spondylitis Disease Activity Index of 8.7, all HLA-B27 positive, with 11 (41%) having spinal ankylosis, were studied for 54 weeks. The qualification for initial and ongoing infliximab treatment was defined by the Australian Pharmaceutical Benefit Schedule (PBS), and 5 mg/kg of infliximab was given at 0 week (baseline), repeated at 2 and 6 weeks and every 6 weeks thereafter. At each time point, PBS-mandated and international consensus response measures were completed. Disease activity and outcome measures for spinal ankylosis subgroup and those who did not have spinal ankylosis were cross-sectionally compared at baseline and 1 year. RESULTS: Patients with spinal ankylosis tended to be older (P = 0.01). Although the subgroup with spinal ankylosis had higher baseline activity scores, the only significant difference between the subgroups was the degree of morning stiffness (P = 0.04). By 54 weeks, all patients including the subgroup with spinal ankylosis fulfilled the PBS criteria for continuation of treatment. Majority of patients including the subgroup with spinal ankylosis achieved the various international consensus response measures. Patients with spinal ankylosis also experienced significant improvements in health-related quality of life, with majority returning to full-time employment by 1 year. CONCLUSION: In real-life clinical practice, patients with established disease with spinal ankylosis and high levels of inflammation and disease activity can achieve a major clinical response with infliximab.
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Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfaRESUMO
OBJECTIVES: This study was conducted to evaluate the antidermatophytic activity of 48 extracts obtained from medicinal plants (Cibotium barometz, Melastoma malabathricum, Meuhlenbeckia platyclada, Rhapis excelsa, Syzygium myrtifolium, Vernonia amygdalina) and marine algae (Caulerpa sertularioides, Kappaphycus alvarezii) against Trichophyton rubrum and Trichophyton interdigitale (ATCC reference strains), and the cytotoxicity using African monkey kidney epithelial (Vero) cells. Active plant extracts were screened for the presence of phytochemicals and tested against clinical isolates of Trichophyton tonsurans. METHODS: Six different extracts (hexane, chloroform, ethyl acetate, ethanol, methanol and water) were obtained from each plant or algae sample using sequential solvent extraction. The antidermatophytic activity for the extracts was assessed using a colourimetric broth microdilution method. The viability of Vero cells was measured by Neutral Red uptake assay. RESULTS: All the extracts (except the water extracts of V. amygdalina, C. sertularioides and K. alvarezii) showed antidermatophytic activity against Trichophyton spp. The minimum fungicidal concentration (MFC) ranges for the plant extracts against T. rubrum and T. interdigitale are 0.0025-2.50 and 0.005-2.50mg/mL, respectively. The algae extracts exhibited lower potency against both species, showing MFC ranges of 0.08-2.50 and 0.31-2.50mg/mL, respectively. The ethanol and methanol extracts from the leaves of R. excelsa, and the methanol and water extracts from the leaves of S. myrtifolium were highly active (MFC<0.1mg/mL) and with high selectivity indices (SI>2.8) against reference strains of T. rubrum and T. interdigitale, and most of the clinical isolates of T. tonsurans. Phytochemical analysis indicates the presence of alkaloids, anthraquinones, flavonoids, saponins, tannins, phenolics and triterpenoids in the extracts. CONCLUSIONS: The medicinal plant extracts exhibited stronger antidermatophytic activity compared to the algae extracts. The leaves of R. excelsa and S. myrtifolium are potential sources of new antidermatophytic agents against Trichophyton spp.
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Antifúngicos , Arthrodermataceae/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Alga Marinha/química , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Arthrodermataceae/crescimento & desenvolvimento , Arthrodermataceae/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Chlorocebus aethiops , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Células VeroRESUMO
Diabetes is an independent risk factor for development of heart failure and has been associated with poor outcomes in these patients. The prevalence of diabetes continues to rise. Using routine HbA1c measurements on inpatients at a tertiary hospital, we aimed to investigate the prevalence of diabetes amongst patients hospitalised with decompensated heart failure and the association of dysglycaemia with hospital outcomes and mortality. 1191 heart failure admissions were identified and of these, 49% had diabetes (HbA1c ≥ 6.5%) and 34% had pre-diabetes (HbA1c 5.7-6.4%). Using a multivariable analysis adjusting for age, Charlson comorbidity score (excluding diabetes and age) and estimated glomerular filtration rate, diabetes was not associated with length of stay (LOS), Intensive Care Unit (ICU) admission or 28-day readmission. However, diabetes was associated with a lower risk of 6-month mortality. This finding was also supported using HbA1c as a continuous variable. The diabetes group were more likely to have diastolic dysfunction and to be on evidence-based cardiac medications. These observational data are hypothesis generating and possible explanations include that more diabetic patients were on medications that have proven mortality benefit or prevent cardiac remodelling, such as renin-angiotensin system antagonists, which may modulate the severity of heart failure and its consequences.
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Diabetes Mellitus/epidemiologia , Hemoglobinas Glicadas/análise , Insuficiência Cardíaca/sangue , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Pacientes Internados , Tempo de Internação/estatística & dados numéricos , Masculino , Readmissão do Paciente/estatística & dados numéricos , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Análise de SobrevidaRESUMO
BACKGROUND: Etanercept reduces disease activity in adults with chronic rheumatoid arthritis (RA) who are resistant to other therapies. Medicare Australia Pharmaceutical Benefit Scheme subsidized treatment (since August 2003) restricts etanercept availability to a most drug-resistant RA population. The aim of the study was to assess the efficacy of etanercept in this unique group after 12 months of therapy. METHODS: A prospective study of the first 50 consecutive private practice, adult RA patients whom were commenced on etanercept. The primary efficacy measures included short form 36 scores, Disease Activity Score 28, American College of Rheumatology (ACR) response improvement in per cent and the ACR individual core set components at baseline, 3 and 12 months. Analysis was by intention to treat. RESULTS: There was significant improvement in all mean short form 36 component scores (P < 0.05) and all ACR core set component scores (P < 0.05) comparing 12 months to baseline. The disease activity score 28 also significantly fell from baseline at both 3 and 12 months (P < 0.05). The ACR 20% response significantly improved (P < 0.05) both at baseline to 3 months 92% (81.2, 96.9) and to 12 months 80% (67.0, 88.8). Serious adverse events occurred in 16%. At 12 months 88% completed treatment. CONCLUSION: Etanercept therapy will, by 3 and 12 months, significantly improve the short form 36, disease activity score 28, ACR 20% response and core set components. Our results are similar to international studies using etanercept in efficacy and tolerance despite our cohort being more resistant to preceding drug therapy. Etanercept offers this unique active severe refractory late RA Australian population a new therapeutic option to control their disease.
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Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/uso terapêutico , Medição da Dor/efeitos dos fármacos , Receptores do Fator de Necrose Tumoral/uso terapêutico , Índice de Gravidade de Doença , Adulto , Idoso , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Austrália/epidemiologia , Etanercepte , Feminino , Humanos , Imunoglobulina G/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Mice that are immune-suppressed by thymectomy and by sequential treatment with 1-beta-D-arabinofuranosylcytosine and whole body irradiation may be used as hosts for generation of human tumor xenografts. We have studied the effect of various additional methods of immune suppression on the formation of tumors after i.m. injection and on the formation of lung colonies after i.v. injection with the human MGH-U1 bladder cancer cell line. Success of transplantation was improved by treatment of immune-suppressed animals with either heterologous antilymphocyte serum or a monoclonal anti-Thy-1.2 antibody. Success of lung colony formation was also improved by antilymphocyte serum but not by monoclonal anti-Thy-1.2 antibody. Admixture of heavily irradiated cells (10(6)) to the viable inoculum of tumor cells in addition to antilymphocyte serum treatment improved the success of i.m. transplantation but not that of lung colony formation. Treatment with corticosteroids or treatment with carrageenan to suppress macrophage activity added toxicity and did not improve the success of xenografting. Immune suppression decreased the natural killer cell activity of normal mice and treatment with antiinterferon to further suppress natural killer cells may also enhance xenograft formation. Administration of cyclosporin A to normal mice allowed the growth of a single xenograft but was not a useful method for immunosuppression. The success of xenografting into immune-deprived mice was superior to that for two strains of nude mice maintained in our laboratory, and i.v. injection of tumor cells did not lead to lung colonies in these nude mice. Immune-deprived mice are a useful alternative to nude mice for the study of xenografts derived from human tumor cell lines and may allow the study of experimental lung metastases.
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Terapia de Imunossupressão/métodos , Neoplasias Pulmonares/secundário , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Animais , Soro Antilinfocitário/farmacologia , Carragenina/farmacologia , Ciclofosfamida/farmacologia , Ciclosporinas/farmacologia , Citarabina/farmacologia , Estradiol/farmacologia , Feminino , Células Matadoras Naturais/imunologia , Masculino , Metilprednisolona/farmacologia , Camundongos , Camundongos Endogâmicos CBA , Timectomia , Transplante Heterólogo , Irradiação Corporal TotalRESUMO
This study addresses the contributions of specific retinoid receptors during all-trans-retinoic acid (RA)-mediated differentiation and growth suppression of human embryonal carcinoma cells. The pleiotropic effects of RA are mediated by retinoic acid receptors (RARs) and retinoid X receptors (RXRs), members of the nuclear receptor family of transcription factors. After RA-treatment the multipotent human embryonal carcinoma cell line NTERA-2 clone D1 (NT2/D1) displays limited proliferative potential, reduced tumorigenicity, and morphologic and immunophenotypic neuronal maturation. RARgamma over-expression in NT2/D1 cells signals mesenchymal NT2/D1 terminal differentiation while RARalpha and RARbeta do not and RARgamma overcomes retinoid resistance in an NT2/D1 clone (NT2/D1-RI) having deregulated RARgamma expression. Since RARgamma transfectants do not display neuronal maturation, this study sought to identify cooperating retinoid receptors engaged in NT2/D1 differentiation. Through gain of function experiments, this report highlights RXRbeta as playing an important role along with RARgamma in signaling differentiation of NT2/D1 cells. Stable over-expression of RXRbeta, but not RXRalpha or RXRgamma, was found to signal NT2/D1 growth suppression and to induce a non-neuronal morphology and immunophenotype. Notably, co-transfection of RARgamma and RXRbeta resulted in marked growth suppression and for the first time, expression of typical neuronal markers of NT2/D1 differentiation. To clarify the role of RXRbeta and RARgamma in this differentiation program, a modified transient fibroblast growth factor-4 (FGF4) promoter-enhancer reporter assay that reflects effective RA-mediated differentiation of NT2/D1 cells was employed. Transfection of RARgamma or RXRbeta in NT2/D1 cells augments transcriptional repression of the FGF4 reporter and RARgamma and RXRbeta co-transfection markedly repressed reporter activity, indicating the combined role of these receptors in RA-induced NT2/D1 differentiation. Taken together, these findings reveal specific retinoid receptors must cooperate to signal terminal growth suppression and maturation of NT2/D1 cells. Since the transcriptional repression of FGF4 is coupled to the effective maturation of human embryonal carcinoma cells, the described co-transfection strategy should prove useful to identify genes with positive or negative effects on the differentiation program of these tumor cells.
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Carcinoma Embrionário/metabolismo , Receptores do Ácido Retinoico/metabolismo , Tretinoína/farmacologia , Diferenciação Celular , Divisão Celular , Dimerização , Fator 4 de Crescimento de Fibroblastos , Fatores de Crescimento de Fibroblastos/biossíntese , Fatores de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Inibidores do Crescimento , Humanos , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Receptores do Ácido Retinoico/genética , Proteínas Recombinantes/metabolismo , Receptores X de Retinoides , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Parasitic nematodes infect billions of people world-wide, often causing chronic infections associated with high morbidity. The greatest interface between the parasite and its host is the cuticle surface, the outer layer of which in many species is covered by a carbohydrate-rich glycocalyx or cuticle surface coat. In addition many nematodes excrete or secrete antigenic glycoconjugates (ES antigens) which can either help to form the glycocalyx or dissipate more extensively into the nematode's environment. The glycocalyx and ES antigens represent the main immunogenic challenge to the host and could therefore be crucial in determining if successful parasitism is established. This review focuses on a few selected model systems where detailed structural data on glycoconjugates have been obtained over the last few years and where this structural information is starting to provide insight into possible molecular functions.
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Infecções por Nematoides/imunologia , Animais , Sequência de Carboidratos , Epitopos/metabolismo , Hexoses/metabolismo , Dados de Sequência Molecular , Infecções por Nematoides/parasitologia , Toxocara/imunologiaRESUMO
Previous studies have shown that polymerized [14C]arabinan can be synthesized from polyprenylphosphate-[14C]arabinose by the particulate enzymes of Mycobacterium smegmatis [R.E. Lee, K. Mikusová, P.J. Brennan and G.S Besra (1995) J. Am. Chem. Soc. 117, 11829-11832]. In the present investigation, the [14C]arabinan product was biochemically characterized. Sizing chromatography revealed a molecular weight consistent with that expected from mature arabinan. Digestion of the [14C]arabinan with a mixture of arabinases produced oligo[14C]arabinoside fragments including hexa[14C]arabinoside and tetra[14C]arabinoside which originated from the non-reducing terminal regions of the polymer, and di[14C]arabinoside from the internal regions of the polymer. These arabinoside fragments represent the major known structural motifs that comprise the arabinan segment of arabinogalactan and lipoarabinomannan. The presence of [14C]arabinose in both the internal and external regions of the [14C]arabinan suggests that polyprenylphosphate-arabinose is the major, and perhaps the only, donor of arabinosyl residues in mycobacteria.
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Mycobacterium/enzimologia , Polissacarídeos/biossíntese , Parede Celular/enzimologia , Glicosídeo Hidrolases , Peso Molecular , Pentosiltransferases/isolamento & purificação , Pentosiltransferases/metabolismo , Polímeros , Polissacarídeos/químicaRESUMO
PURPOSE: This multicenter phase II trial investigated the efficacy and toxicity of a combination of the novel intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl (DPPE), and doxorubicin in patients with anthracycline-naïve metastatic breast cancer. Preclinical models and early single institutional studies suggested DPPE could potentiate the cytotoxicity of doxorubicin. PATIENTS AND METHODS: Forty-two women, 32 to 77 years old (median, 59 years), with anthracycline-naïve metastatic breast cancer were treated. Patients may have had one previous regimen of nonanthracycline chemotherapy, either in the adjuvant or metastatic disease treatment setting. DPPE (6 mg/kg) was administered as an 80 minute intravenous infusion with doxorubicin (60 mg/m(2)) given intravenously over the last 20 minutes of the DPPE infusion. Patients were premedicated with an antiemetic and sedating regimen. The DPPE/doxorubicin treatment was given every 21 days for a maximum of seven cycles. RESULTS: All 42 patients were assessable. Overall, toxicity was comparable to that expected with doxorubicin alone, with the exception of DPPE-related motion sickness, mild hallucinations, and cerebellar signs at the time of the infusion. These CNS side effects were manageable in an ambulatory care setting, improved with subsequent cycles of treatment, and did not usually require hospitalization. Four patients developed febrile neutropenia. Thirty-five patients received four or more cycles of chemotherapy. The overall response rate was 52.5% (95% confidence interval, 36% to 68%), with 9.5% complete responses (n = 4), 43% partial responses (n = 18), and 38% of patients with stable disease (n = 16). CONCLUSION: The antitumour effects of DPPE/doxorubicin the 52.5% response rate seems encouraging, particularly in consideration of the fact that a recently reported randomized National Cancer Institute of Canada Clinical Trials Group trial using single-agent doxorubicin 60 mg/m(2) in one of the treatment arms achieved a 31% response rate. Thus, a randomized phase III trial of doxorubicin versus doxorubicin plus DPPE is being conducted in this clinical setting.
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Antineoplásicos/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Éteres Fenílicos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Canadá , Doxorrubicina/efeitos adversos , Quimioterapia Combinada , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
INTRODUCTION: Uterine papillary serous carcinoma (UPSC), a high-grade tumour, is known to be associated in some cases with an identifiable intraepithelial neoplasia (IEN) component. Biomarker studies incorporating this latter component are not well documented. One aim of the present study was to compare levels of immunohistochemical (IHC) expression of p53 tumour suppressor gene and bcl-2 oncoprotein between UPSC and IEN, as well as normal endometrium to determine its biologic significance. The other major aim was to determine if these IHC results have any bearing on survival data in this tumour. MATERIALS AND METHODS: An immunoreactivity score was assigned for examination of p53 and bcl-2 expression in a total of 21 cases of UPSC, 9 with an evaluable IEN component and 11 with associated non-neoplastic endometrium. Statistical analysis of IHC results was performed, in addition to correlation with survival data and disease stage. RESULTS: p53 was identified in 16/21 cases of UPSC (76%) and 8/9 cases of IEN (89%), and no cases of normal endometrium. By contrast, bcl-2 was positive in all normal endometria with less expression in UPSC leaving 15/21 (71%) cases positive, and in IEN, leaving 5/9 (55%) of cases positive. Differences in immunoreactive scores for both p53 and bcl-2 between UPSC and benign glands, as well as between IEN and benign glands reached statistical significance with P values of 0.006 and 0.014 for p53, and 0.003 and 0.027 for bcl-2 respectively. There was no statistical significance between values for UPSC and IEN. Cox regression analysis found no statistically significant relationship between patient survival time in early and late stages of disease, and p53 and bcl-2 immunoscores. CONCLUSIONS: The lack of a significant difference between the bcl-2 and p53 values for both UPSC and IEN suggests that these molecular alterations occur at an early stage of tumour pathogenesis. A potential advantage of the use of immunohistochemical markers is their application to routinely processed surgical specimens. In this case, bcl-2 and p53 were applied in UPSC to determine any potential significance, but neither marker proved to be a useful predictor of survival time or disease stage.
Assuntos
Cistadenocarcinoma Papilar/patologia , Endométrio/patologia , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Uterinas/patologia , Atrofia/patologia , Biomarcadores Tumorais/análise , Biópsia por Agulha , Estudos de Casos e Controles , Cistadenocarcinoma Papilar/genética , Cistadenocarcinoma Papilar/mortalidade , Feminino , Genes p53/genética , Humanos , Imuno-Histoquímica , Probabilidade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Neoplasias Uterinas/genética , Neoplasias Uterinas/mortalidadeRESUMO
INTRODUCTION: In addition to surveillance practices, chemoprevention and prophylactic surgery can reduce the risk of cancer in individuals at high risk. Sociocultural factors may have a role to play in such decision making. Little is known regarding the factors that play a role in decision making in Singapore. MATERIALS AND METHODS: One hundred and two individuals at normal risk completed a questionnaire on the concept of chemoprevention and prophylactic surgery. The results were analysed using the convenience sampling method. RESULTS: Participants were mostly Chinese (94.1%). More than 90% of the respondents answered the section on prophylactic surgery and chemoprevention. Thirty-eight individuals (41.3%) would not consider prophylactic surgery, while 42 (45.7%) would not consider prophylactic surgery now but might consider it in the future. Twenty-five individuals (26.9%) would not consider chemoprevention by taking a medication, 57% would not consider it now but might in the future. CONCLUSION: A cross-sectional public view suggests that medical prophylaxis is likely to be more acceptable to the general public compared to surgical prophylaxis.