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1.
Geroscience ; 42(2): 633-651, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31927681

RESUMO

Naked mole-rats (NMRs) have amongst the longest lifespans relative to body size of any known, non-volant mammalian species. They also display an enhanced stress resistance phenotype, negligible senescence and very rarely are they burdened with chronic age-related diseases. Alternative splicing (AS) dysregulation is emerging as a potential driver of senescence and ageing. We hypothesised that the expression of splicing factors, important regulators of patterns of AS, may differ in NMRs when compared to other species with relatively shorter lifespans. We designed assays specific to NMR splicing regulatory factors and also to a panel of pre-selected brain-expressed genes known to demonstrate senescence-related alterations in AS in other species, and measured age-related changes in the transcript expression levels of these using embryonic and neonatal developmental stages through to extreme old age in NMR brain samples. We also compared splicing factor expression in both young mouse and NMR spleen and brain samples. Both NMR tissues showed approximately double the expression levels observed in tissues from similarly sized mice. Furthermore, contrary to observations in other species, following a brief period of labile expression in early life stages, adult NMR splicing factors and patterns of AS for functionally relevant brain genes remained remarkably stable for at least two decades. These findings are consistent with a model whereby the conservation of splicing regulation and stable patterns of AS may contribute to better molecular stress responses and the avoidance of senescence in NMRs, contributing to their exceptional lifespan and prolonged healthspan.


Assuntos
Envelhecimento , Longevidade , Ratos-Toupeira , Fatores de Processamento de RNA , Envelhecimento/genética , Animais , Encéfalo , Longevidade/genética , Camundongos , Fenótipo , Fatores de Processamento de RNA/fisiologia
2.
Transbound Emerg Dis ; 64(6): 1790-1800, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27637887

RESUMO

Coronaviruses are a diverse group of viruses that infect mammals and birds. Bats are reservoirs for several different coronaviruses in the Alphacoronavirus and Betacoronavirus genera. They also appear to be the natural reservoir for the ancestral viruses that generated the severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus outbreaks. Here, we detected coronavirus sequences in next-generation sequence data created from Eonycteris spelaea faeces and urine. We also screened by PCR urine samples, faecal samples and rectal swabs collected from six species of bats in Singapore between 2011 and 2014, all of which were negative. The phylogenetic analysis indicates this novel strain is most closely related to lineage D Betacoronaviruses detected in a diverse range of bat species. This is the second time that coronaviruses have been detected in cave nectar bats, but the first coronavirus sequence data generated from this species. Bat species from which this group of coronaviruses has been detected are widely distributed across SE Asia, South Asia and Southern China. They overlap geographically, often share roosting sites and have been witnessed to forage on the same plant. The addition of sequence data from this group of viruses will allow us to better understand coronavirus evolution and host specificity.


Assuntos
Betacoronavirus/isolamento & purificação , Quirópteros/virologia , Infecções por Coronavirus/veterinária , Reservatórios de Doenças/veterinária , Interações Hospedeiro-Patógeno , Animais , Betacoronavirus/genética , Evolução Biológica , Infecções por Coronavirus/virologia , Reservatórios de Doenças/virologia , Ecologia , Fezes/virologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Masculino , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Singapura/epidemiologia , Análise Espaço-Temporal , Urina/virologia
3.
Water Sci Technol ; 67(2): 340-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23168633

RESUMO

To date, little information is known about the operation of the enhanced biological phosphorus removal (EBPR) process in tropical climates. Along with the global concerns on nutrient pollution and the increasing array of local regulatory requirements, the applicability and compliance accountability of the EBPR process for sewage treatment in tropical climates is being evaluated. A sequencing batch reactor (SBR) inoculated with seed sludge from a conventional activated sludge (CAS) process was successfully acclimatized to EBPR conditions at 28 °C after 13 days' operation. Enrichment of Candidatus Accumulibacter phosphatis in the SBR was confirmed through fluorescence in situ hybridization (FISH). The effects of operational pH and influent C:P ratio on EBPR were then investigated. At pH 7 or pH 8, phosphorus removal rates of the EBPR processes were relatively higher when operated at C:P ratio of 3 than C:P ratio of 10, with 0.019-0.020 and 0.011-0.012 g-P/g-MLVSS•day respectively. One-year operation of the 28 °C EBPR process at C:P ratio of 3 and pH 8 demonstrated stable phosphorus removal rate of 0.020 ± 0.003 g-P/g-MLVSS•day, corresponding to effluent with phosphorus concentration <0.5 mg/L. This study provides the first evidence on good EBPR activity at relatively high temperature, indicating its applicability in a tropical climate.


Assuntos
Carbono/análise , Recuperação e Remediação Ambiental/métodos , Recuperação e Remediação Ambiental/normas , Fósforo/análise , Fósforo/isolamento & purificação , Clima Tropical , Anaerobiose , Técnicas de Cultura Celular por Lotes , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Estudos de Viabilidade , Concentração de Íons de Hidrogênio , Malásia , Compostos Orgânicos/análise , Fosfatos/análise , Esgotos , Solubilidade , Fatores de Tempo
4.
Knee Surg Sports Traumatol Arthrosc ; 13(3): 203-8, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15127185

RESUMO

Patellae in small knees, or after severe patellar erosion, may be vulnerable to fracture after resection during arthroplasty. The patellar remnant may be thin, while the polyethylene component has a standard thickness. Anterior patellar bone strain was measured in cadaver knees loaded via the quadriceps, from 0 to 90 degrees flexion, with the patella intact, and after resections to 16, 13 and 11 mm thick and replacement by an 8-mm-thick polyethylene component. Strain increased significantly with knee flexion with constant 500 N quadriceps tension. Resection caused significant changes from intact values in knee flexion and extension and no significant effect at 30 degrees flexion. In flexion, bending caused the anterior surface to become more convex, with high tensile bone strains. In extension, resection caused negative anterior strains, representing bending in the opposite direction, with large tensile strains on the cut posterior surface. For normal activities, such as rising from a chair (1.8 kN quadriceps tension) the patella appears safe against fracture with a minimal resection to 16 mm thick. An eroded patella resected to 11 mm thickness may be at risk of fracture with that loading.


Assuntos
Artroplastia do Joelho/métodos , Fraturas Ósseas/etiologia , Patela/lesões , Patela/cirurgia , Artroplastia do Joelho/efeitos adversos , Cadáver , Humanos , Prótese do Joelho/efeitos adversos , Fatores de Risco , Singapura
5.
Singapore Med J ; 44(7): 347-51, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-14620726

RESUMO

INTRODUCTION: A prospective trial was carried out in simultaneous bilateral total knee replacement to compare the outcome of resurfaced versus non-surfaced patella. METHODS: Thirty-five patients between 1997 and 2002 had simultaneous bilateral total knee replacement with resurfaced patella on the left and non-resurfaced patella on the right knee using the same implant in both. RESULTS: There were 29 females and six males with a mean age of 65.3 years. Mean follow-up was 3.18 years. There was no significant difference between the resurfaced and non-resurfaced knees with respect to the overall Knee Society clinical score (p = 0.093 preoperative, 0.310 postoperative) or the pain (p = 0.715 preoperative, 0.395 postoperative) or function subscores (p = 0.126 preoperative, 0.317 postoperative). The postoperative range of motion was 109 and 110 degrees for the resurfaced patella and non-resurfaced patella respectively (p = 0.894). The post-operative knee scores between patients with or without pre-operative anterior knee pain (p = 0.238) and between those who were obese and non-obese (p = 0.387) were not significantly different. 82.9% of patients felt that the resurfaced knee and 80% felt that the non-resurfaced knee were much better than before. There was no major preference for either knee for climbing stairs and getting out of chair. CONCLUSION: The functional and symptomatic outcome of total knee replacement with or without patella resurfacing is the same in the local population. Also, the present study demonstrated no evidence that the weight of the patient or the presence of preoperative anterior knee pain should be considered as factors in the decision to resurface the patella.


Assuntos
Artroplastia do Joelho/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Patela/cirurgia , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
6.
Can J Physiol Pharmacol ; 80(2): 142-9, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11934257

RESUMO

The human placenta is a highly invasive tumor-like structure in which a subpopulation of placental trophoblast cells known as the "extravillous trophoblast" (EVT) invades the uterine decidua and its vasculature to establish adequate fetal-maternal exchange of molecules. By utilizing in vitro-propagated short-lived EVT cell lines we found that molecular mechanisms responsible for their invasiveness are identical to those of cancer cells; however, unlike cancer cells, their proliferation, migration, and invasiveness in situ are stringently controlled by decidua-derived transforming growth factor (TGF)-beta. By SV40T antigen transfection of normal EVT cells followed by a forced crisis regimen in culture we produced an immortalized premalignant derivative that is hyperproliferative, hyperinvasive, and deficient in gap-junctional intercellular communication. Both premalignant and malignant EVT (JAR and JEG-3 choriocarcinoma) cell lines were found to be TGF-beta-resistant. Using these cell lines, we investigated genetic changes responsible for transition of the normal EVT cells to premalignant and malignant phenotype. Hyperinvasiveness in both cases resulted from a downregulation of tissue inhibitor of metalloprotease (TIMP)-1 and plasminogen activator inhibitor (PAI)-1 genes. In contrast to normal EVT cells, both cell types failed to upregulate these genes in response to TGF-beta. Loss of TGF-beta response in malignant EVT cells was explained by the loss of expression of Smad3 gene. Differential mRNA display of normal and premalignant EVT cells identified up- and down-regulation of numerous known or novel genes in premalignant EVT cells, with potential oncogenic and (or) tumor-suppressor functions, e.g., loss of fibronectin and insulin-like growth factor binding protein (IGFBP-5). Premalignant EVT cells also lost IGF receptor type 2 (IGFR-II). IGFBP-5 was shown to be a negative regulator of IGF-1-induced proliferation of premalignant EVT cells, so that loss of IGFBP-5 as well as IGFR-II permitted their unrestricted proliferation in an IGF-I-rich microenvironment of the fetal-maternal interface. The present model may be a good prototype for identifying genetic changes underlying epithelial tumor progression.


Assuntos
Neoplasias/patologia , Placentação , Trofoblastos/fisiologia , Linhagem Celular , Coriocarcinoma/patologia , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Invasividade Neoplásica , Lesões Pré-Cancerosas/genética , Gravidez , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/fisiologia , Trofoblastos/citologia , Células Tumorais Cultivadas
7.
J Arthroplasty ; 17(1): 56-61, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11805925

RESUMO

With patellar thickness averaging 24.0 mm and 21.9 mm in Singapore men and women undergoing total knee arthroplasty, achievement of precut thickness is difficult if the recommended residual bony thickness of 15 mm is maintained. We retrospectively compared the clinical outcome of 56 patellae resurfaced 12 mm (mean residual thickness, 13.7 mm). Both groups were comparable in terms of demographic characteristics, presentation, precut patellar thickness, and operative details (P> .05). Knee scores (P= .627), extensor mechanism function (P= .625), and postoperative range of motion (P= .344) were comparable. Differences in the overall (P= .167) and patellar (P= .061) complication rates as determined by chi-square test on the SPSS 10.0 program were not significant, although there were 4 patella-related complications in group 2. Increased patella-related complications may be associated with an excessive patellar composite of the patellofemoral articulation. A residual patellar thickness of <12 mm did not appear to affect the clinical outcome in this series.


Assuntos
Artroplastia do Joelho/métodos , Patela/patologia , Patela/cirurgia , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores Sexuais , Resultado do Tratamento
8.
Int J Cancer ; 94(5): 674-84, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11745462

RESUMO

Tumorigenesis results from genetic alterations that occur in a stepwise manner giving rise to cells with increasingly cancer-like characteristics. We used in vitro propagated first trimester human extravillous trophoblast (EVT) cells to identify genetic changes responsible for the transition of the EVT from a normal to premalignant stage. The model used consisted of a normal invasive EVT (HTR8) cell line and its premalignant derivative (RSVT2/C) generated by transfection with the SV40 Tag and selected using a forced crisis regimen. RSVT2/C display increased proliferative, migratory and invasive behavior, unresponsiveness to anti-proliferative and anti-invasive signals of TGFbeta and a deficiency in gap junctional intercellular communication. These cells, however, were unable to form colonies on soft agar or tumors in nude mice and are thus defined as premalignant. Differential display revealed 18 gene sequences, 7 with unknown and 11 with known identity, showing altered expression between the normal HTR8 and premalignant RSVT2/C cell lines. The known sequences include the potential tumor suppressors insulin-like growth factor binding protein (IGFBP)-5 and fibronectin (FN) and potential protooncogenes such as chromokinesin (KIF4), alternative splicing factor (SF2), dynein, DNA polymerase epsilon (DNApol epsilon) and NF-kappaB activating kinase (NAK). The role of the remaining 4 genes upregulated in the premalignant EVT is presently unknown and these are FK506 binding protein (FKBP) 25, histone protein (HP1Hs)-gamma, nucleoporin (Nup) 155 and an 82 kDa acidic human protein. The functional role of IGFBP-5 was examined in the control of proliferation, migration and invasiveness of RSVT2/C cells measured in vitro. IGFBP-5 alone had no effect on these properties of RSVT2/C cells. Furthermore, unlike normal EVT cells, RSVT2/C cells exhibited refractoriness to the migration stimulating signals of IGF-II, which was explained by the loss or downregulation of the IGF type 2 receptor (IGF-R2). RSVT2/C cells, however, expressed the IGF type 1 receptor (IGF-R1) and responded to IGF-I by increased proliferation. This response was blocked with increasing concentrations of IGFBP-5. These results suggest that the loss of IGFBP-5 and possibly IGF-R2, both of which can sequester IGF-I from IGF-R1, permits unhindered proliferation of the premalignant EVT in an IGF-I rich environment of the fetal-maternal interface. The functions of the other differentially expressed genes, some of which are essential for cell cycle progression or cell survival require further investigation.


Assuntos
Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Lesões Pré-Cancerosas/genética , Neoplasias Trofoblásticas/genética , Sequência de Bases , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Feminino , Fibronectinas/fisiologia , Expressão Gênica , Humanos , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fator de Crescimento Insulin-Like II/farmacologia , Dados de Sequência Molecular , Invasividade Neoplásica , Gravidez , RNA Mensageiro/análise
10.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(3 Pt 1): 031108, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11308631

RESUMO

We consider d-dimensional systems with nonintegrable, algebraically decaying pairwise interactions. It is shown that, upon the introduction of periodic boundary conditions and a long-distance cutoff in the interaction range, the bulk thermodynamics can be obtained rigorously by means of a Kac-potential treatment, leading to an exact, mean-field-like theory. This explains various numerical results recently obtained for finite systems in the context of "nonextensive thermodynamics," and in passing exposes a strong regulator dependence not discussed in these studies. Our findings imply that, contrary to some claims, Boltzmann-Gibbs statistics are sufficient for a standard description of this class of nonintegrable interactions.

11.
J Arthroplasty ; 16(1): 102-6, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11172278

RESUMO

The outcome of 109 consecutive total knee arthroplasties in 86 diabetic patients was studied. There were 73 women and 13 men, with a mean age of 69 years (range, 56-84 years). All the patients were followed for at least 36 months. The mean follow-up period was 42 months (range, 36-60 months). In the early postoperative period (< or =1 month), the overall wound infection rate was 7.3% (8 knees). The risk of deep joint infection was 5.5% (6 knees). Of the patients, 15% (17 knees) developed a urinary tract infection after the operation. The superficial and deep infection rates were higher when compared with a similar study in the general population. Maximum precautions should be taken for diabetic patients undergoing total knee arthroplasties.


Assuntos
Artroplastia do Joelho , Diabetes Mellitus , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Infecções Relacionadas à Prótese/microbiologia , Reoperação , Infecção da Ferida Cirúrgica/microbiologia , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia
12.
Mol Carcinog ; 29(2): 103-11, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11074607

RESUMO

Recent studies have shown that expression levels of the multidrug resistance gene MDR1, which encodes the drug transporter P-glycoprotein, correlate with prognostic outcomes of certain tumor types. These findings suggest that expression of MDR1 may affect tumor behaviors. To address this issue further, we investigated the expression of mdr1a, a human MDR1 homolog, on the development of hepatocellular carcinoma in a transgenic mouse model carrying the liver-targeted expression of human hepatitis-B virus (HBV) surface antigen. The pathogenetic program was compared in HBV mice carrying either mdr1a(+/+) or mdr1a(-/-). We found that the expressions of proliferative activity markers, Ki67 nuclear antigen, and proliferating cell nuclear antigen were elevated in mdr1a(-/-) mice younger than 10 wk in comparison with those in the same age group of wild-type animals. Replication in the hepatic population as determined by bromodeoxyuridine incorporation tended to support observation that mdr1a(-/-) mice exhibited elevated labeling indices in this age group. Moreover, histologic staining and flow-cytometric analysis showed that the mdr1a(-/-) animals exhibited a higher cell population with polyploidy than did the mdr1a(+/+) counterparts of the same age. However, no significant differences in the expression of the liver-injury markers serum alanine transaminase and aspartate transaminase were observed. Although our results showed that absence of mdr1a expression is correlated with modest enhanced proliferative characteristics in the livers at stage before the development of hepatocellular carcinoma, the overall life spans between these two strains of mice were not significantly different. The implication of these findings to the role of P-glycoprotein in tumor development and cancer chemotherapy is discussed.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Vírus da Hepatite B/genética , Antígeno Ki-67/biossíntese , Neoplasias Hepáticas Experimentais/genética , Antígeno Nuclear de Célula em Proliferação/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/biossíntese , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Divisão Celular/genética , Cruzamentos Genéticos , Modelos Animais de Doenças , Resistência a Múltiplos Medicamentos/genética , Feminino , Expressão Gênica , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/imunologia , Antígeno Ki-67/genética , Fígado/enzimologia , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/virologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ploidias , Antígeno Nuclear de Célula em Proliferação/genética
13.
Ann Acad Med Singap ; 29(4): 439-41, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11056771

RESUMO

INTRODUCTION: The aims of this paper were to study the incidence of deep vein thrombosis following total knee replacement in an Asian population and to evaluate the role of low molecular weight heparin for deep vein thrombosis in this setting. MATERIALS AND METHODS: We prospectively studied two groups of 100 consecutive patients undergoing total knee replacement separately. Group 1 did not receive any low molecular weight heparin and group 2 received low molecular weight heparin, nodraparin calcium (Fraxiparine) according to body weight. The sex distribution, age group, weight, preoperative knee and function scores, and postoperative rehabilitation were similar for both groups. A single ultrasound technician performed ultrasound duplex scan of both lower limbs on the seventh postoperative day. RESULTS: The incidence of deep vein thrombosis in group 1 was 14% (14 patients, 5 proximal vein thromboses and 9 distal vein thromboses) while in group 2, no patients developed deep vein thrombosis. There was no increased incidence, either local or systemic, of major bleeding complications with the use of low molecular weight heparin. CONCLUSION: While the incidence of deep vein thrombosis following total knee replacement in an Asian population appears lower compared to Western populations, the use of low molecular weight heparin for thromboprophylaxis appears to further reduce the incidence without major bleeding complications.


Assuntos
Anticoagulantes/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Nadroparina/uso terapêutico , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/farmacologia , Povo Asiático , Feminino , Hemorragia/induzido quimicamente , Humanos , Incidência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Nadroparina/farmacologia , Estudos Prospectivos , Singapura , Ultrassonografia Doppler , Trombose Venosa/diagnóstico por imagem
14.
Int J Cancer ; 86(5): 725-30, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10797297

RESUMO

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cell-based vaccines are currently one of the major forms of cancer vaccines. However, the preparation of GM-CSF-transduced autologous tumor vaccines is time-consuming and technically challenging. In addition, the host antigen presenting cells, rather than the tumor vaccine cells themselves, present tumor-specific antigens and prime the host T cells. Therefore, we tested the efficacy of antigen-specific allogeneic tumor vaccines. We used human papillomavirus 16 (HPV-16) E7 protein as a model tumor antigen, which is associated with the development of most cervical carcinoma. B16, a C57BL/6 (H-2(b)) derived melanoma cell line, was genetically engineered to produce GM-CSF alone (B16GM), HPV-16 E7 alone (B16E7), or both (B16GME7). These vaccine cells were injected into BALB/c (H-2(d)) mice (10(6) cells/mouse). Two weeks later, mice were challenged with 10(5) live HPV-16 E7(+) BL-1 (H-2(d)) tumor cells and monitored for tumor progression twice weekly. To determine the effective cell population in the antitumor immunity elicited by B16GME7, we carried out in vivo antibody depletion experiments using CD4 and CD8 specific antibodies. In addition, as a measure of the immune responses produced by B16GME7, we performed an in vitro cytotoxic T lymphocyte assay using a standard chromium release method. We found that all of the mice vaccinated with B16GME7 remained tumor free 49 days post-BL-1 challenge. In contrast, mice vaccinated with B16GM and B16E7 did not show any tumor protection against a similar dose of BL-1 cells. Furthermore, the antitumor immunity produced by B16GME7 was dependent on both CD4 and CD8 T cells. In addition, E7-specific cytotoxic T lymphocyte activity could be readily demonstrated in mice immunized with B16GME7. These results suggest that allogeneic tumor cells transduced with GM-CSF and the tumor antigen, HPV-16 E7, cannot only generate an E7-specific cytotoxic T lymphocytes response in vitro, but can also elicit a potent antitumor immune response against an E7 expressing tumor in vivo.


Assuntos
Vacinas Anticâncer/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Neoplasias Experimentais/terapia , Proteínas Oncogênicas Virais/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/administração & dosagem , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Imunoterapia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/mortalidade , Proteínas Oncogênicas Virais/biossíntese , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus , Linfócitos T Citotóxicos/imunologia , Transdução Genética , Células Tumorais Cultivadas
15.
Chin J Physiol ; 43(4): 185-90, 2000 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-11292184

RESUMO

It is known that lung vagal C-fiber afferents play an important role in eliciting the tachypneic response to pulmonary air embolism (PAE), and can be subgrouped as those with low resistance (LRC) and those with high resistance (HRC) to perivagal capsaicin. In this study, we investigated the relative contributions of vagal LRC and HRC C-fiber afferents to the PAE-induced tachypneic response. Phrenic activity was recorded from 10 anesthetized, paralyzed, and artificially ventilated dogs. PAE was induced by infusion of air into the vein (2 ml/min, 1 ml/kg). During control conditions, induction of PAE produced a shortening in expiratory duration with no significant change in inspiratory duration, resulting in tachypnea. The PAE-induced tachypneic response was totally abolished by perivagal capsaicin treatment with a method (capsaicin concentration, 6 mg/ml; treatment duration, 25-30 min) that blocks the conduction of LRC C-fiber afferents, but not that of HRC C-fiber afferents. This tachypneic response was not affected by cooling of both vagi to a temperature (4.5 degrees C) that blocks the conduction of HRC C-fiber afferents, but not that of LRC C-fiber afferents. A bilateral cervical vagotomy virtually eliminated this tachypneic response. These results suggest that LRC C-fiber afferents are responsible for eliciting the reflex tachypneic response to PAE, whereas HRC C-fiber afferents play no vital role.


Assuntos
Embolia Aérea/fisiopatologia , Pulmão/inervação , Fibras Nervosas/fisiologia , Mecânica Respiratória/fisiologia , Nervo Vago/fisiologia , Anestesia , Animais , Capsaicina/farmacologia , Temperatura Baixa , Cães , Pulmão/fisiopatologia , Nervo Frênico/fisiologia , Nervo Vago/citologia , Nervo Vago/efeitos dos fármacos
16.
Artigo em Inglês | MEDLINE | ID: mdl-11970479

RESUMO

The influence of immobile filler particles (spheres, fibers, platelets) on polymer-blend phase separation is investigated computationally using a generalization of the Cahn-Hilliard-Cook (CHC) model. Simulation shows that the selective affinity of one of the polymers for the filler surface leads to the development of concentration waves about the filler particles at an early stage of phase separation in near critical composition blends. These "target" patterns are overtaken in late-stage phase separation by a growing "background" spinodal pattern characteristic of blends without filler particles. The linearized CHC model is used to estimate the number of composition oscillations emanating from isolated filler particles. In far-off-critical composition blends, an "encapsulation layer" grows at the surface of the filler rather than a target pattern. The results of these simulations compare favorably with experiments on filled phase-separating ultrathin blend films in which the filler particles are immobilized on a solid substrate.

17.
Chin J Physiol ; 42(4): 219-25, 1999 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-10707897

RESUMO

Perivagal capsaicin treatment and vagal cooling are two techniques that have been widely used to study the respiratory reflexes mediated by lung vagal C-fibers because they can block the neural conduction of unmyelinated fibers. We hypothesized that there are two subgroups of lung vagal C-fibers which have different vulnerabilities to blockades by these two techniques. To test this hypothesis, afferent activity arising from lung vagal C-fibers was recorded in 29 anesthetized, paralyzed, and artificially ventilated dogs. Afferent C-fiber activity was recorded before and after various concentrations of perivagal capsaicin treatment or before and during various temperatures of vagal cooling. Of the 89 lung vagal C-fibers studied, 73 fibers were classified as the group of "low resistance" to capsaicin, while the other 16 were classified as the group of "high resistance". The former group differed from the latter due to their afferent activity being blocked at relatively low concentrations of perivagal capsaicin and at relatively low temperatures of vagal cooling. Our results suggest that lung vagal C-fibers can be categorized into two subgroups, based upon their different blocking thresholds for perivagal capsaicin and vagal cooling. Our data may provide information for researchers to further differentiate the respiratory reflexes originating from these two subgroups of lung vagal C-fibers.


Assuntos
Capsaicina/farmacologia , Pulmão/inervação , Fibras Nervosas/efeitos dos fármacos , Nervo Vago/citologia , Nervo Vago/fisiologia , Animais , Temperatura Corporal , Temperatura Baixa , Cães , Relação Dose-Resposta a Droga , Fibras Nervosas/fisiologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Reflexo/fisiologia , Respiração Artificial , Limiar Sensorial , Nervo Vago/efeitos dos fármacos
18.
Am J Physiol ; 274(2): E238-45, 1998 02.
Artigo em Inglês | MEDLINE | ID: mdl-9486153

RESUMO

The acute effects of thyroid hormones on glucocorticoid secretion were studied. Venous blood samples were collected from male rats after they received intravenous 3,5,3'-triiodothyronine (T3) or thyroxine (T4). Zona fasciculata-reticularis (ZFR) cells were treated with adrenocorticotropic hormone (ACTH), T3, T4, ACTH plus T3, or ACTH plus T4 at 37 degrees C for 2 h. Corticosterone concentrations in plasma and cell media, and also adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells in the presence of 3-isobutyl-1-methylxanthine, were determined. The effects of thyroid hormones on the activities of steroidogenic enzymes of ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Administration of T3 and T4 suppressed the basal and the ACTH-stimulated levels of plasma corticosterone. In ZFR cells, both thyroid hormones inhibited ACTH-stimulated corticosterone secretion, but the basal corticosterone was inhibited only with T3 > 10(-10) M or T4 > 10(-8) M. Likewise, T3 or T4 at 10(-7) M inhibited the basal- and ACTH-stimulated levels of intracellular cAMP. Physiological doses of T3 and T4 decreased the activities of 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase, and 11 beta-hydroxylase. These results suggest that thyroid hormones counteract ACTH in adrenal steroidogenesis through their inhibition of cAMP production in ZFR cells.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Corticosterona/biossíntese , AMP Cíclico/biossíntese , Hormônios Tireóideos/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , 3-Hidroxiesteroide Desidrogenases/metabolismo , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Animais , Colforsina/farmacologia , Corticosterona/sangue , Corticosterona/metabolismo , Masculino , Inibidores de Fosfodiesterase/farmacologia , Ratos , Ratos Sprague-Dawley , Esteroide 11-beta-Hidroxilase/metabolismo , Esteroide 21-Hidroxilase/metabolismo , Hormônios Tireóideos/farmacologia , Tiroxina/sangue , Tiroxina/farmacologia , Tiroxina/fisiologia , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Tri-Iodotironina/fisiologia
19.
J Bone Joint Surg Am ; 80(1): 70-5, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9469311

RESUMO

We reviewed the long-term results of 126 consecutive total hip arthroplasties performed with cement in eighteen men and 108 women who had an acute fracture of the femoral neck. The patients had a mean age of seventy-five years (range, thirty-nine to eighty-nine years) at the time of the operation and were followed for a minimum of 10.1 years (or until the patient died or had a revision operation) and a maximum of 20.4 years. The median duration of follow-up was 8.8 years for all patients and 15.7 years for the twenty-two patients who were alive at the end of the study period. Six hips (5 per cent) were revised because of aseptic loosening. Survivorship analysis revealed that the probability of survival of the prosthesis without revision (with 95 per cent confidence intervals) was 95 per cent (91 to 99 per cent) at five years, 94 per cent (88 to 98 per cent) at ten years, 89 per cent (79 to 97 per cent) at fifteen years, and 84 per cent (66 to 97 per cent) at twenty years. Of the 118 patients who were alive at the one-year postoperative examination, 117 (99 per cent) had no pain or mild pain and eighty-one (69 per cent) had regained or had an improvement in the preoperative level of function. At the latest follow-up examination, eighty-seven (86 per cent) of the 102 patients who were available still had no pain or only mild pain. Twenty-six patients (21 per cent) had had perioperative medical complications, and twenty-one patients (17 per cent) had had operative complications, including thirteen patients (10 per cent) who had had a dislocation of the hip. Total hip arthroplasty performed in elderly patients for the treatment of an acute fracture of the femoral neck was associated with a higher rate of complications than usually is reported for hemiarthroplasty in such patients. However, the total hip arthroplasty provided good clinical results and was associated with long-term survival of the prosthesis.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
20.
Singapore Med J ; 39(7): 303-5, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9885691

RESUMO

BACKGROUND: Twenty-two consecutive revisions for failed metal-backed patellar components following total knee arthroplasty in 17 patients were retrospectively reviewed. All had similar total condylar knee prosthesis inserted with retention of the posterior cruciate ligament and resurfacing of the patella with a metal-backed component. There were 3 male and 14 female patients. RESULTS: The mean time to failure of the patellar component was 60 months (range 26 to 93 months). The majority of patients presented with metallic crepitus (86.4%) and knee pain (72.7%). At surgery, full thickness polyethylene wear exposing the metal-backing was present in 81.8% with surface damage of the femoral components present in 40.9%. All 22 cases underwent successful isolated patellar component revision with all polyethylene patellar components. CONCLUSION: Resurfacing of the patella in total knee arthroplasty with metal-backed patellar components carries a significant risk of early failure and the use of these components is no longer practised at our institution.


Assuntos
Artroplastia do Joelho/instrumentação , Prótese do Joelho , Osteoartrite/cirurgia , Patela/cirurgia , Falha de Prótese , Idoso , Feminino , Seguimentos , Humanos , Masculino , Metais , Pessoa de Meia-Idade , Polietilenos , Reoperação
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