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1.
Zhonghua Wei Chang Wai Ke Za Zhi ; 26(3): 260-267, 2023 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-36925126

RESUMO

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.


Assuntos
Exenteração Pélvica , Neoplasias Pélvicas , Humanos , Exenteração Pélvica/métodos , Neoplasias Pélvicas/cirurgia , Estudos Retrospectivos , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias
2.
Eur Rev Med Pharmacol Sci ; 23(5): 2013-2019, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30915744

RESUMO

OBJECTIVE: Increasing studies have indicated the important functions of long non-coding RNAs (lncRNAs) in tumorigenesis and progression including hepatocellular carcinoma (HCC). The study aims to explore the role of long non-coding RNA AK001796 in HCC progression. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (QRT-PCR) analysis was performed to examine the lncRNA AK001796 expression in 73 cases of human HCC tissue samples and matched adjacent normal tissues. Besides, the relationship between lncRNA AK001796 expression and clinicopathologic characteristics was analyzed. Overall survival (OS) curves of patients were constructed by the Kaplan-Meier methods. Multivariate Cox regression analysis was used to evaluate independent risk factors affecting HCC prognosis. Cell proliferation and invasion abilities are analyzed by cell counting kit-8 (CCK-8) and transwell invasion assays. RESULTS: We showed that the lncRNA AK001796 expression was significantly up-regulated in HCC tissues and cell lines, compared to their controls, respectively. Higher lncRNA AK001796 expression closely correlated with tumor size (p<0.05), TNM stage (p<0.05) and the poor overall survival (OS) rate of HCC patients (p<0.05). Besides, multivariate Cox regression analysis found that lncRNA AK001796 expression was identified as an independent risk factor for HCC prognosis. In vitro, we showed that lncRNA AK001796 knockdown markedly suppressed cell proliferation and cell invasion abilities. CONCLUSIONS: Our results suggested that lncRNA AK001796 acts as a predictor of HCC prognosis and may provide an important clinical value for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Proliferação de Células/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Modelos de Riscos Proporcionais , Regulação para Cima
3.
Phys Chem Chem Phys ; 18(40): 28033-28039, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27711517

RESUMO

Technically important wide band-gap semiconductors such as GaN, AlN, ZnO and SiC are crystallized in polar structures. Taking SiC as an example, we investigate the effect of surface polarity on the wetting behavior by water using experiments and molecular dynamic simulations. It is found that the contact angle (CA) of deionized water on the carbon-face (C-face) is significantly larger than that on the silicon-face (Si-face) for both 6H-SiC and 4H-SiC, while the CA of tetrachloromethane is almost the same on these two faces. This finding clearly indicates that polar interactions between water and SiC induce such a large difference in the CA. Extensive molecular dynamics simulations suggest that a larger CA on the C-face than that on the Si-face is resulted from the different charge agglomeration on the two faces. These results will not only be helpful in improving the state of the art processes such as rinsing and wet etching in device fabrication, but also offer a reliable method to determine the polarity of SiC crystals quickly, simply, accurately and nondestructively, which is easily extendable for the measurement of other polar crystals.

4.
Genet Mol Res ; 14(2): 3062-70, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25966070

RESUMO

The aim of this study was to evaluate the control of blood glucose and glycosylated hemoglobin A1c (HbA1c) and its influencing factors, in elderly type 2 diabetic mellitus (T2DM) patients undergoing comprehensive management. After years of comprehensive prevention of and control measures for diabetes, elderly T2DM patients who were receiving long-term health care were comprehensively evaluated through an annual physical examination. In addition to routine health examination, the patients were required to undergo HbA1c measurement. Among 688 patients, 652 were men and 36 were women, with a mean age of 78.2 ± 9.1 years. The average HbA1c was 6.6 ± 0.9%. A total of 50.6% of the patients had HbA1c <6.5%, whereas 76.3% had HbA1c <7.0%. Among all patients, 77.1, 46.4, 66.1, 67.8, 36.3, and 57.4% achieved the target total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), blood pressure, and body mass index (BMI) levels, respectively. The duration of disease and type of treatment, as well as the LDL, HDL, TG, BMI, and blood pressure levels, were significantly associated with HbA1c control. No patient was admitted because of ketoacidosis or hyperosmolar nonketotic diabetic coma in 10 years. Approximately half of the T2DM patients achieved the target HbA1c level. The more effective blood glucose control observed in our study compared with previous studies can be attributed to the effective monitoring of medical conditions and comprehensive management of patients.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/terapia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Idoso , Idoso de 80 Anos ou mais , Colesterol/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino
5.
Intern Med J ; 42(3): 329-32, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22432986

RESUMO

We describe an elderly male patient who presented with fever of unknown origin and refractory hyponatraemia. Following (18) fluorine-fluorodeoxyglucose positron emission tomography/computed tomography scan and core adrenal biopsy, the diagnosis of diffuse large B-cell non-Hodgkin lymphoma with pituitary and bilateral adrenal involvement was confirmed. After chemotherapy, his symptoms resolved, and all the lesions shrank significantly.


Assuntos
Glândulas Suprarrenais/patologia , Linfoma Difuso de Grandes Células B/patologia , Hipófise/patologia , Glândulas Suprarrenais/diagnóstico por imagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Evolução Fatal , Febre de Causa Desconhecida/etiologia , Humanos , Hiponatremia/etiologia , Hiponatremia/fisiopatologia , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Imagem Multimodal , Hipófise/diagnóstico por imagem , Sistema Hipófise-Suprarrenal/fisiopatologia , Tomografia por Emissão de Pósitrons , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Tomografia Computadorizada por Raios X , Ultrassonografia , Vincristina/administração & dosagem , Vincristina/efeitos adversos
6.
Curr Pharm Des ; 14(5): 454-64, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18289072

RESUMO

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of ferroheme metabolic pathway, which has the functions of anti-oxidation, anti-inflammatory, anti-apoptosis and anti-smooth muscle hyperplasia. Furthermore, HO-1 exerts a protective action in the diseases mediated by effector T lymphocytes such as T helper (Th) 1, Th2 and Th17. In addition, regulatory T cells (Treg) control the activity of CD4+CD25- effector cells in a suppressive manner. Numerous studies indicate that the protective action of HO-1 in diseases is through CD4+CD25+ Treg. This paper will review the current research and understanding of HO-1's role in T cells-mediated immunoregulation.


Assuntos
Heme Oxigenase-1/imunologia , Imunidade Celular , Linfócitos T/imunologia , Animais , Heme Oxigenase-1/fisiologia , Humanos , Doenças do Sistema Imunitário/enzimologia , Doenças do Sistema Imunitário/imunologia , Linfócitos T/enzimologia , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia , Células Th1/enzimologia , Células Th1/imunologia , Células Th2/enzimologia , Células Th2/imunologia
7.
Electrophoresis ; 22(6): 1016-20, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11358122

RESUMO

Limb muscles of eutherian (placental) mammals express a slow and three fast isoforms of myosin heavy chain (MyHC), but little is known about marsupial MyHCs. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of limb MyHCs from seven marsupial species, spanning two orders, revealed four components, each of which specifically cross-reacted in Western blots with a monoclonal antibody (mAb) against a corresponding eutherian MyHC. For all seven species, the relative mobility of the band identified by each mAb matched that in the rat, suggesting that the four are homologous to eutherian slow, 2B, 2X and 2A MyHCs, respectively, in the order of decreasing mobility. Immunohistochemical analysis of fast marsupial limb muscles identitied four different fiber populations whose relative fiber size spectra (IIA

Assuntos
Marsupiais , Cadeias Pesadas de Miosina/análise , Animais , Western Blotting/métodos , Eletroforese em Gel de Poliacrilamida/métodos , Extremidades , Músculo Esquelético/química
8.
Am J Clin Nutr ; 72(3): 804-8, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10966903

RESUMO

BACKGROUND: Sesamin, a nonfat constituent of sesame oil, inhibits Delta(5)-desaturase activity, resulting in accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid (AA) and consequently decreases the formation of proinflammatory 2-series prostaglandins. OBJECTIVE: We sought to determine whether dietary supplementation with sesamin augments the antiinflammatory effects of dietary linseed oil in rats. DESIGN: We investigated the effects of continuous tube feedings of emulsions containing safflower oil or linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver fatty acid composition and on endotoxin-induced production of prostaglandin E(2), 6-keto-prostaglandin F(1alpha), and tumor necrosis factor alpha (TNF-alpha) by whole blood from rats (n = 6 per diet group). RESULTS: We found a significant accumulation of DGLA only in the liver phospholipids of animals fed SO+ and LO+ (1.8 +/- 0.2 and 1.4 +/- 0.3 mol%, respectively), which suggests that sesamin inhibited Delta(5)-desaturation of n-6 fatty acids. These changes were associated with significant reductions in plasma prostaglandin E(2) concentrations in animals fed SO+ compared with those fed SO (P: < 0. 05). Despite a significant reduction in tissue AA content in the LO group, the prostaglandin E(2) concentrations did not differ significantly from those of the SO group. Plasma concentrations of TNF-alpha were significantly lower (P: < 0.05) in the animals fed LO+ than in those fed SO (199 +/- 48 and 488 +/- 121 ng/L, respectively). CONCLUSION: These data indicate that in rats, tube feedings of diets containing sesamin exerted antiinflammatory effects that were augmented by concurrent consumption of linseed oil.


Assuntos
Anti-Inflamatórios/farmacologia , Gorduras na Dieta/farmacologia , Suplementos Nutricionais , Dioxóis/farmacologia , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Prostaglandinas/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , 6-Cetoprostaglandina F1 alfa/biossíntese , Animais , Peso Corporal/efeitos dos fármacos , Dinoprostona/biossíntese , Emulsões , Ácidos Graxos/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
9.
J Muscle Res Cell Motil ; 21(7): 673-80, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11227794

RESUMO

The masseter muscle of eutherian grazing mammals typically express beta or slow myosin heavy chain (MyHC). Myosins in the masseter of 4 species of kangaroos and a slow limb muscle of one of them were compared with their cardiac myosin by pyrophosphate and sodium dodecyl sulphate (SDS) gel electrophoresis, immunoblotting and immunohistochemistry. It was found that ventricular muscle contains three isoforms homologous to V1 (alpha-MyHC homodimer), V2 (heterodimer) and V3 (beta-MyHC homodimer) of eutherian cardiac muscle, and that the masseter contained V1, with traces of V2 and V3, in great contrast to eutherian ruminants, which express only V3. A polyclonal antibody (anti-KJM) was raised in rabbits against red kangaroo masseter myosin. After cross-absorption against limb muscle myofibrils, anti-KJM specifically reacted in Westerns with MyHCs from masseter but not limb muscles, and immunohistochemically with masseter, but not limb muscle fibers. In pyrophosphate Western blots, anti-KJM reacted with V1 but not with V3. However, a monoclonal antibody specific for eutherian slow myosin stained all kangaroo slow muscle fibers but only weakly stained scattered fibers in the masseter. The SDS-PAGE revealed that light chain composition of masseter and ventricular myosins is identical, but isoforms of both light chains of kangaroo limb slow myosin were observed. These results confirm that kangaroo jaw muscle express alpha-MyHC rather than beta-MyHC. The difference in MyHC gene expression between marsupial and eutherian grazers may be related to the fact that kangaroos are not ruminants, and have only a single chance to comminute food into fine particles, hence the need for the greater speed and power of muscle contraction associated with V1 containing muscle fibers.


Assuntos
Macropodidae , Músculo Esquelético/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Animais , Arcada Osseodentária
11.
Cell Transplant ; 8(6): 661-71, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10701495

RESUMO

Although adenoviral vector-mediated gene transfer has significant potential for gene therapy, host immune responses to virally expressed proteins and small insert capacity may limit its clinical application. In order to overcome these disadvantages, a new adenoviral vector that lacks all viral genes has been developed. Using the green fluorescent (GFP) gene as a reporter gene, we investigated the efficiency of gene transfer by this all-viral-genes-deleted and minimal cis-element remaining adenoviral vector (miniAd-GFP) in islets in vitro and ex vivo, and compared it with the E1-deleted adenoviral vector (E1-GFP). One day after in vitro infection, GFP was expressed in both miniAd-GFP- and E1-GFP-infected islets. The percentage of GFP-positive single cells was not significantly different between miniAd-GFP-infected islets and E1-GFP-infected islets. When these islets were transplanted into syngeneic diabetic mice, both miniAd-GFP- and E1-GFP-infected islet grafts reversed diabetes, and normal blood glucose levels were maintained for over 20 weeks posttransplantation. Mild lymphocyte infiltration was found in all E1-GFP-infected islet grafts at all time points. However, this was not seen in most miniAd-GFP-infected islet grafts. Our results indicate that gene transfer by an adenoviral vector that lacks all viral genes is as efficient as E1-deleted adenoviral vector-mediated gene transfer in islets. Furthermore, this adenoviral vector might be less immunogeneic than the E1-deleted adenoviral vector.


Assuntos
Adenoviridae/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Transplante das Ilhotas Pancreáticas , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Experimental/cirurgia , Expressão Gênica , Genes Reporter , Genes Virais , Proteínas de Fluorescência Verde , Insulina/metabolismo , Transplante das Ilhotas Pancreáticas/imunologia , Transplante das Ilhotas Pancreáticas/fisiologia , Proteínas Luminescentes/genética , Camundongos , Camundongos Endogâmicos BALB C , Transplante Isogênico
12.
Artigo em Inglês | MEDLINE | ID: mdl-9774171

RESUMO

Eicosapentaenoic acid (EPA) and the non-methylene interrupted fatty acids (NMIFA) displace arachidonic acid (AA: 20:4omega6 -5,8,11,14) in the membrane phospholipids. Unlike EPA (20:5omega3 -5,8,11,14,17), the NMIFA (20:3omega6 -5,11,14 and 20:4omega3 -5,11,14,17) lacking the delta-8 double bond are not substrates for the formation of eicosanoids. For 20 days, the mice were fed diets containing 5wt% dietary fats from various sources. The magnitudes in the production of eicosanoids and cytokines produced in response to an intraperitoneal injection of endotoxin in mice fed menhaden fish oil (MO) diets enriched with EPA were compared with those maintained on juniper oil (JO) containing NMIFA or on safflower oil (SO), a major source of the AA precursor, linoleic acid. The levels of PGE2, 6-keto-PGF1alpha and TXB2 were markedly lower (P < 0.01) in animals fed either MO or JO diets compared to the controls. The plasma levels of tumor necrosis factor (TNF)-alpha were significantly higher (P < 0.05) with a concomitant decrease of interleukin (IL)-6 and of IL-10 in mice fed MO or JO diets (P < 0.01) compared to those fed SO diet. These data suggest that the effects of consuming NMIFA of JO despite their inability to form eicosanoids are similar to those of feeding EPA which forms biologically active alternate metabolites.


Assuntos
Citocinas/sangue , Eicosanoides/sangue , Óleos de Peixe/farmacologia , Lipopolissacarídeos/toxicidade , Óleos de Plantas/farmacologia , 6-Cetoprostaglandina F1 alfa/sangue , Animais , Dinoprostona/sangue , Ácidos Graxos Insaturados/metabolismo , Feminino , Injeções Intraperitoneais , Interleucina-10/sangue , Interleucina-6/sangue , Juniperus , Lipopolissacarídeos/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Óleo de Cártamo/farmacologia , Tromboxano B2/sangue , Fator de Necrose Tumoral alfa/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-9610840

RESUMO

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.


Assuntos
Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lignanas , Lipopolissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Ácido alfa-Linolênico/administração & dosagem , Animais , Anticolesterolemiantes/farmacologia , Dessaturase de Ácido Graxo Delta-5 , Gorduras Insaturadas na Dieta/administração & dosagem , Dinoprostona/metabolismo , Dioxóis/farmacologia , Relação Dose-Resposta a Droga , Ácidos Graxos Dessaturases/efeitos dos fármacos , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6 , Ácidos Graxos Insaturados/metabolismo , Feminino , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/metabolismo
14.
Genetics ; 147(2): 435-50, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9335584

RESUMO

The sequenced yeast genome offers a unique resource for the analysis of eukaryotic cell function and enables genome-wide screens for genes involved in cellular processes. We have identified genes involved in cell surface assembly by screening transposon-mutagenized cells for altered sensitivity to calcofluor white, followed by supplementary screens to further characterize mutant phenotypes. The mutated genes were directly retrieved from genomic DNA and then matched uniquely to a gene in the yeast genome database. Eighty-two genes with apparent perturbation of the cell surface were identified, with mutations in 65 of them displaying at least one further cell surface phenotype in addition to their modified sensitivity to calcofluor. Fifty of these genes were previously known, 17 encoded proteins whose function could be anticipated through sequence homology or previously recognized phenotypes and 15 genes had no previously known phenotype.


Assuntos
Genes Fúngicos , Saccharomyces cerevisiae/genética , Membrana Celular/metabolismo , Elementos de DNA Transponíveis , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Fenótipo
15.
Int Arch Allergy Immunol ; 114(2): 153-60, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9338609

RESUMO

Sesamin, present in sesame seed oil (SSO), can inhibit delta-5-desaturase activity and cause accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid, and subsequently decrease production of dienoic eicosanoids. The effects of diets containing both SSO and Quil A, a saponin that emulsifies fats and potentiates the immune responses, were also studied. A mixture of oils having a fatty-acid composition similar to that of SSO served as a control diet. The levels of docosapentaenoic acid in mice fed Quil-A-supplemented diets and of DGLA in those fed SSO diets were markedly higher in the liver. These changes were associated with a significant reduction in the plasma prostaglandin-E(1+2) and thromboxane-B2 levels in response to an intraperitoneal injection of a lethal dose of lipopolysaccharide (LPS) endotoxin (LD50 20 mg/kg). The levels of interleukin (IL-)6 were elevated and those of IL-1beta were decreased in mice consuming Quil-A-supplemented diets. The IL-10 levels that were elevated in all mice after LPS exposure, remained higher (even at 9 h) only in those fed Quil-A-supplemented diets, but declined rapidly in others. During a 48-hour observation period following LPS injection, all control animals died, and survival was 40% in the SSO group, and 27 and 50%, respectively, in those fed Quil-A-supplemented control and SSO diets. These data suggest that SSO and Quil A when present in the diet exerted cumulative effects that resulted in a decrease in the levels of dienoic eicosanoids with a reduction in IL-1beta and a concomitant elevation in the levels of IL-10 that were associated with a marked increase in survival in mice.


Assuntos
Eicosanoides/biossíntese , Interleucinas/biossíntese , Lignanas , Saponinas/farmacologia , Óleo de Gergelim/farmacologia , Choque Séptico/dietoterapia , Animais , Suplementos Nutricionais , Dinoprostona/biossíntese , Dioxóis/farmacologia , Ácidos Graxos/análise , Feminino , Fígado/química , Membranas/química , Camundongos , Camundongos Endogâmicos BALB C , Saponinas de Quilaia , Choque Séptico/imunologia , Choque Séptico/mortalidade , Análise de Sobrevida , Tromboxano B2/biossíntese
16.
Genome ; 40(1): 151-64, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9061922

RESUMO

The DNA sequence and preliminary functional analysis of a 103-kbp section of the left arm of yeast chromosome I is presented. This region, from the left telomere to the LTE1 gene, can be divided into two distinct portions. One portion, the telomeric 29 kbp, has a very low gene density (only five potential genes and 21 kbp of noncoding sequence), does not encode any "functionally important" genes, and is rich in sequences repeated several times within the yeast genome. The other portion, with 37 genes and only 14.5 kbp of noncoding sequence, is gene rich and codes for at least 16 "functionally important" genes. The entire gene-rich portion is apparently duplicated on chromosome XV as an extensive region of partial gene synteney called a cluster homology region. A function can be assigned with varying degrees of precision to 23 of the 42 potential genes in this region; however, the precise function is know for only eight genes. Nineteen genes encode products presently novel to yeast, although five of these have homologs elsewhere in the yeast genome.


Assuntos
Cromossomos Fúngicos , Genes Fúngicos , Família Multigênica , Saccharomyces cerevisiae/genética , Sequência de Bases , DNA Fúngico , Dados de Sequência Molecular , Fases de Leitura Aberta , Homologia de Sequência do Ácido Nucleico
17.
Immunology ; 84(3): 446-52, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7751029

RESUMO

Prostaglandin E2 (PGE2) appears to regulate macrophage cytokine production through the stimulatory GTP-binding protein (Gs protein)-mediated cyclic AMP (cAMP)-dependent transmembrane signal transduction pathway. In this study, we used PGE2, cholera toxin (CT; a direct G alpha s protein stimulator) and 8-bromo-cAMP (a membrane permeable cAMP analogue) to stimulate this pathway, and investigated their influence on cytokine gene expression in lipopolysaccharide (LPS)-activated human macrophages. The mRNA expression for interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 were determined employing reverse transcription polymerase chain reaction (RT-PCR) using specific primers. We demonstrated that PGE2, CT and 8-bromo-cAMP inhibited the LPS-induced gene activation of TNF-alpha and IL-1 alpha, and had no effect on the gene activation of IL-1 beta and IL-8. Further, our data indicate that PGE2 suppressed the gene activation of IL-6 following LPS stimulation, but neither CT nor 8-bromo-cAMP had an effect. These data suggest that PGE2 alters LPS-stimulated gene activation of only some of the early macrophage cytokines, and does so either by a Gs transmembrane cAMP-dependent or an independent system.


Assuntos
Citocinas/biossíntese , Dinoprostona/farmacologia , Macrófagos/imunologia , Transdução de Sinais/efeitos dos fármacos , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Adulto , Células Cultivadas , Toxina da Cólera/farmacologia , Citocinas/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Lipopolissacarídeos/imunologia , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Masculino , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética
18.
Biochim Biophys Acta ; 1214(3): 333-9, 1994 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-7918617

RESUMO

The effects of a short-term (5 days) continuous intragastric tube feeding of diets containing n - 6 polyunsaturated fatty acids (PUFA) from safflower oil (SO) or n - 3 PUFA from menhaden oil (MO) on the production of proinflammatory mediators, and on the number of animals surviving after an intravenous injection of lipopolysaccharide (LPS) were investigated in rats. The phospholipid fatty acid composition of cell membranes from several organs and of plasma were also analyzed. No marked differences in the number of animals surviving or in the production of tumor necrosis factor-alpha were observed between the 2 groups of animals. However, 90 min after LPS exposure the plasma levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha decreased significantly (40% and 60%, respectively) for the group of rats fed MO diet compared to those fed SO diet (P < 0.05). Following continuous infusion of liquid MO diet, the amount of arachidonic acid (AA) detected was significantly lower in plasma (23%), spleen (43%), lungs (41%), and liver (38%), but was unchanged in the heart tissues. The percent of eicosapentaenoic acid (EPA) incorporated into phospholipids of plasma, spleen, lungs, liver, and heart were 7.6, 4.4, 2.1, 7.2, and 1.1%, respectively. These data indicate that after continuous MO feeding, a significant decrease in the production of proinflammatory eicosanoids was associated with a marked reduction in AA content. Further, these data suggest that nutritional intervention may have a therapeutic potential to ameliorate clinical symptoms due to excessive productions of eicosanoids during acute septic complications.


Assuntos
Gorduras Insaturadas na Dieta/administração & dosagem , Eicosanoides/biossíntese , Nutrição Enteral , Ácidos Graxos/análise , Choque Séptico/terapia , Animais , Gorduras Insaturadas na Dieta/farmacologia , Dinoprostona/biossíntese , Eicosanoides/química , Lipopolissacarídeos , Masculino , Fosfolipídeos/química , Ratos , Ratos Sprague-Dawley , Choque Séptico/metabolismo , Choque Séptico/mortalidade , Taxa de Sobrevida , Distribuição Tecidual , Fator de Necrose Tumoral alfa/biossíntese
19.
Life Sci ; 55(11): PL193-8, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8072381

RESUMO

Prostaglandins (PGs) play an important role in the regulation of the host's immune responses to infection and inflammation. However, the mechanisms through which the PGs regulate immune functions are not well known. In the present study, we investigated the T cell specific mitogen Concanavalin A (Con A) induced mouse splenocyte proliferation in a serum free condition in vitro in the presence of absence of different doses of PGE2, indomethacin, cholera toxin and forskolin. The Con A induced splenocyte proliferative responses were significantly inhibited following the addition of PGE2 and were markedly enhanced in the presence of indomethacin (PG synthase inhibitor). As with PGE2, both cholera toxin and forskolin, which increase intracellular cyclic AMP by activating stimulatory GTP binding protein (Gs protein) and adenylate cyclase respectively, inhibited splenocyte proliferation in a dose dependent manner. These data indicate that PGE2 down regulated mitogen induced splenocyte proliferation and that blocking the production of endogenous PGs potentiated T-cell mitogen response. Further, these findings suggest that PGE2 regulation of splenocyte proliferation is due to increasing intracellular cAMP through G protein transmembrane regulation of adenylate cyclase. This study also provided a defined experimental model to investigate mechanisms of the regulation of cellular function through the exogenous and endogenous mediators such as PGs and their intracellular signal transductions.


Assuntos
Toxina da Cólera/farmacologia , Colforsina/farmacologia , AMP Cíclico/metabolismo , Dinoprostona/farmacologia , Indometacina/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Adenilil Ciclases/metabolismo , Animais , Células Cultivadas , Concanavalina A , Meios de Cultura Livres de Soro , Relação Dose-Resposta a Droga , Feminino , Proteínas de Ligação ao GTP/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia
20.
Yeast ; 9(5): 543-9, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8322517

RESUMO

The DNA sequence of a region between the LTE1 and CYS3 genes on the left arm of chromosome I from Saccharomyces cerevisiae contains an open reading frame (ORF), YAL017, corresponding to the 5.0 kb FUN31 (Function Unknown Now) transcribed region. The predicted protein from this ORF contains 1358 amino acid residues with a molecular weight of 152,531, and an identifiable serine/threonine protein kinase catalytic domain. When compared with other yeast protein kinases, the Yal017p kinase most resembles the SNF1 serine/threonine protein kinase which is involved in regulating sucrose fermentation genes. The Yal017p kinase shows highest amino acid identities with two mammalian carcinoma-related serine/threonine protein kinases; PIM-1, which shows induced expression in T-cell lymphomas; and p78A1, whose expression is lost in human pancreatic carcinomas. Gene disruption of YAL017 indicates that it is non-essential for growth on glucose.


Assuntos
Genes Fúngicos , Proteínas Serina-Treonina Quinases/genética , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Animais , Cromossomos Fúngicos , DNA Fúngico/genética , Humanos , Camundongos , Dados de Sequência Molecular , Fases de Leitura Aberta , Saccharomyces cerevisiae/enzimologia , Homologia de Sequência de Aminoácidos
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