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1.
Clin Exp Allergy ; 38(8): 1282-9, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18510694

RESUMO

BACKGROUND: Changes in the composition of the gut microbiota have been implicated in the pathogenesis of allergic disorders, suggesting beneficial interactions between the intestinal immune system and specific bacterial strains. Lactobacilli are naturally present within the complex gastrointestinal microbiota of humans and they are currently present in many probiotic supplements. OBJECTIVE: We sought to investigate the role that Lactobacillus casei Shirota (LcS) may play in modulating seasonal allergic rhinitis (SAR). METHODS: The study format was double-blinded, placebo-controlled with 10 SAR sufferers in each group. We have documented and compared changes in immune status arising through the daily ingestion of a milk drink with or without live LcS, over a period of 5 months. Pre-, peak- and post-grass pollen season blood samples were collected for determination of plasma total IgE and grass pollen-specific IgG and IgE levels by an enzyme immunoassay. At the same time, cytokine levels were determined by flow cytometric bead array technology following culture of peripheral blood mononuclear cells for 6 days in the presence or absence of specific grass pollen antigens. RESULTS: Volunteers treated with LcS showed a significant reduction in levels of antigen-induced IL-5, IL-6 and IFN-gamma production compared with volunteers supplemented with placebo. Meanwhile, levels of specific IgG increased and IgE decreased in the probiotic group. CONCLUSION: Changes in antigen-induced production of cytokines were observed in patients treated with probiotics. These data show that probiotic supplementation modulates immune responses in allergic rhinitis and may have the potential to alleviate the severity of symptoms.


Assuntos
Lacticaseibacillus casei/imunologia , Probióticos/administração & dosagem , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/terapia , Administração Oral , Adolescente , Adulto , Alérgenos/imunologia , Citocinas/biossíntese , Método Duplo-Cego , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Pólen/imunologia
2.
Arterioscler Thromb Vasc Biol ; 22(7): 1187-93, 2002 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12117736

RESUMO

OBJECTIVE: We hypothesized that acute hyperglycemia (an independent cardiovascular risk factor) increases the expression of proatherogenic leukocyte adhesion molecule in type 2 diabetes and controls and that the expression of these adhesion molecules would be antioxidant sensitive. METHODS AND RESULTS: Twenty-three type 2 diabetes patients and 13 control patients underwent two oral glucose tolerance tests 14 days apart and took placebo or 800 IU daily of oral alpha tocopherol between tests. Monocyte and neutrophil expression of adhesion molecules Mac-1, LFA-1 and 3, ICAM-1, and VLA-4 were measured at 0, 120, and 240 minutes by using laser flow cytometry. Baseline adhesion molecule expression did not differ between groups, but there was a rapid, highly significant increase (P<0.0001) in the intensity of monocyte Mac-1 expression after a glucose load in both groups. Alpha-tocopherol supplementation reduced only Mac-1 expression in the diabetes group (P=0.03). CONCLUSIONS: Acute glycemic excursions of any degree cause highly significant, rapid increases in monocyte Mac-1 expression in type 2 diabetes patients and controls. Mac-1 mediates leukocyte vascular infiltration and is prothrombotic. These data suggest a mechanism for the link between glycemic excursions and increased vascular event rates.


Assuntos
Antioxidantes/uso terapêutico , Moléculas de Adesão Celular/biossíntese , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/sangue , Monócitos/metabolismo , Neutrófilos/metabolismo , Doença Aguda , Administração Oral , Adulto , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Antígenos CD58/biossíntese , Antígenos CD58/sangue , Moléculas de Adesão Celular/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/complicações , Integrina alfa4beta1 , Integrinas/biossíntese , Integrinas/sangue , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Antígeno-1 Associado à Função Linfocitária/biossíntese , Antígeno-1 Associado à Função Linfocitária/sangue , Antígeno de Macrófago 1/biossíntese , Antígeno de Macrófago 1/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Neutrófilos/patologia , Receptores de Retorno de Linfócitos/biossíntese , Receptores de Retorno de Linfócitos/sangue , Solubilidade , Fator de Necrose Tumoral alfa/metabolismo , alfa-Tocoferol/administração & dosagem , alfa-Tocoferol/sangue , alfa-Tocoferol/uso terapêutico
3.
Leukemia ; 8(11): 1864-70, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7967732

RESUMO

Normal and malignant B-lymphoid cells were studied for CD37 antigen expression with three-color immunofluorescence (IF) in combination with kappa/lambda light chain staining, and by quantitative immunofluorescence utilizing the QIFI test. Peripheral B cells brightly expressed CD37 antigen (median 80-114 x 10(3) molecules/cell). Moderate to high levels (> 20 x 10(3)/cell) of CD37 expression were detected in 364 in 366 cases of peripheral B-cell disorders including all cases of B-ALL, B-cell lymphomas and B-CLL as well as eight of ten cases of PLL. By contrast, slg- B-cell precursors and other cell types in normal bone marrow (BM) were CD37-/CD37dull (< 10 x 10(3) molecules/cell). The negativity for CD37 or only CD37dull expression was confirmed in 180 of 182 cases of precursor B-ALL and 196 cases of non-B malignancies. Among the CD37 cluster, the RFB7 antibody of IgM class showed the weakest binding to non-B cells. In 64 normal samples of blood and BM the CD37+ gated cells showed normal kappa/lambda ratios as expected, while in 100 cases of B malignancy striking changes such as kappa/lambda monoclonality (79%) and aberrant slg- or sigdull expression (21%) were seen among the gated CD37+ B cells. The CD37/kappa/lambda test identified as few as 0.5% kappa+ or lambda- monoclonal B cells admixed to normal BM: circulating B-lymphoma cells were seen in nine patients with morphologically normal blood count. The discrimination of the Kolmogorov-Smirnov (KS) test for kappa/lambda excess was also improved by CD37+ B gating. Thus CD37+ B-cell gating and kappa/lambda analysis is a simple and sensitive routine test, e.g. when combined with autogating on a Cytoron-Absolute cytometer, for identifying malignant B cells in minimally involved BM and blood.


Assuntos
Antígenos CD/análise , Antígenos de Neoplasias , Subpopulações de Linfócitos B/imunologia , Glicoproteínas/análise , Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Leucemia de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Linfoma de Células B/imunologia , Anticorpos Monoclonais , Células Clonais , Citometria de Fluxo , Humanos , Imunofenotipagem , Tetraspaninas
4.
Leukemia ; 9(7): 1191-8, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7543174

RESUMO

The expression of bcl-2 protein that is involved in preventing apoptosis in hemopoietic and other cells was evaluated by quantitative flow cytometry in various subpopulations in the normal fetal bone marrow (FBM) and in different types of acute myelogenous leukemias (AML). In the FBM the highest bcl-2 levels (mean antibody binding capacity 51 x 10(3) molecules/cell) were found in CD34+ intermediate sized blasts and myeloblasts, while a CD34+ subset of CD10+ lymphoblasts had low bcl-2 content (8-10 x 10(3) molecules/cell) and the CD34-, CD10+ lymphoblasts were, as expected from previous studies, bcl-2- (< 5 x 10(3) molecules/cell). Variable levels of bcl-2 (5.1-222 x 10(3)) were found in 43 tested cases of AML. The bcl-2 levels decrease with granulocytic and monocytic differentiation and, accordingly, cases of AML with M1 and M2 features showed significantly higher mean bcl-2 levels than the leukemias with promyelocytic (M3) or myelo-monocytic (M4/M5) features. Nevertheless, in seven cases of AML the bcl-2 levels were higher than seen in the normal FBM cells and none of these patients remain in remission after 2 years. Furthermore, in several AML cases intraclonal heterogeneity was observed. The undifferentiated smaller blasts with Class-IIdim display had higher bcl-2 content than the more differentiated larger blasts with more granular side scatter and Class-bright expression. In the same subsets of AML blasts the proliferative S-G2-M fractions showed a reciprocal correlation to bcl-2 content. Thus the higher bcl-2 levels may give a survival advantage and confer some degree of drug resistance to the least differentiated blast populations. The multi-parameter analysis described in this paper, including a combined bcl-2 and cytokinetic analysis of phenotypically defined subgroups of AML blasts, may detect early population shifts during relapse and also guide combination drug therapy.


Assuntos
Medula Óssea/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Antígenos CD/metabolismo , Antígenos CD34 , Medula Óssea/imunologia , Medula Óssea/patologia , Divisão Celular , Citometria de Fluxo , Antígenos HLA-DR/metabolismo , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Imunofenotipagem , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/patologia , Neprilisina/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2
5.
Transplantation ; 50(5): 823-9, 1990 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1700506

RESUMO

Human naive and memory T cells can be isolated from each other by their CD45RA and CD45RO expression, respectively. This enables the assessment of their differential sensitivities to immunosuppressive agents for the first time. We have investigated the ability of cyclosporine or CD7 and CD25 antibodies to selectively block alloantigen stimulated naive and memory T cells in vitro. CD7 antibodies blocked the proliferation of naive (P less than 0.025) but not memory T cells in a primary MLR. CD25 antibody inhibited both naive and memory subsets but a significantly greater effect was found on the memory T cells (P less than 0.005). The constitutive CD7 and CD25 antigen expression on resting naive or memory T cells was related to the inhibitory activities of these antibodies on both subsets. Accordingly, naive T cells expressed more CD7 antigen than memory cells while memory T cells displayed low levels of CD25 antigen that was absent from naive populations before activation. Cyclosporine, like CD25 antibody, inhibited both subsets in a primary MLR but had a greater effect on memory cells (P less than 0.02). Memory T cells, therefore, are more dependent than naive cells on IL-2 for proliferation. There was great individual variation in the ability of CsA to block the MLR. The simultaneous addition of CD25 or CD7 antibody together with CsA, however, enhanced the MLR inhibition as the effects of all three were additive. This suggested interference by these agents at different points during T cell activation. Thus, in CsA sensitive individuals, one-tenth of the optimal CsA concentration together with CD25 antibody maintained maximum immunosuppression in vitro. These results demonstrate the possibility of using CD7 and CD25 antibodies for selective inhibition of naive or memory T cells and also the possibility of augmenting the inhibition of and reducing the CsA concentration required for clinically effective immunosuppression.


Assuntos
Antígenos de Diferenciação de Linfócitos T/fisiologia , Ciclosporinas/farmacologia , Memória Imunológica/efeitos dos fármacos , Receptores de Interleucina-2/fisiologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Anticorpos Monoclonais/imunologia , Antígenos CD/fisiologia , Antígenos CD7 , Antígenos de Diferenciação/fisiologia , Antígenos de Histocompatibilidade/fisiologia , Humanos , Terapia de Imunossupressão , Isoantígenos/imunologia , Antígenos Comuns de Leucócito , Teste de Cultura Mista de Linfócitos
6.
Leuk Res ; 11(7): 649-54, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3112472

RESUMO

Normal and malignant T cells as well as T-cell hybridomas have frequently been reported to produce factors which stimulate the growth of committed hemopoietic progenitors. One previous report described a lymphokine produced by a T-cell clone which inhibited hemopoietic progenitor cell proliferation. We now describe the simultaneous production of two activities by a Thy-ALL cell line (JM), a sub-line of Jurkat. Two sets of culture conditions were used: the Fauser & Messner and Iscove's assays. We have been able to separate both inhibitory and stimulatory factors for the growth of multipotent and committed bone marrow progenitors (CFU-GEMM, BFU-E, CFU-E and CFU-GM). The stimulatory factor has an apparent mol. wt of less than 30,000 and the inhibitor an apparent mol. wt of 65-80,000. The growth promoting activity for BFU-E and CFU-GEMM could replace that of phytohemagglutinin stimulated leucocyte conditioned medium (PHA-LCM). We do not know if the production of both activities is due to the malignant phenotype or if there is a normal counterpart to JM that could produce both inhibitory and stimulatory factors.


Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Leucemia Linfoide/patologia , Linfocinas/metabolismo , Linfócitos T/metabolismo , Antígenos de Diferenciação de Linfócitos T , Antígenos de Neoplasias/análise , Antígenos de Superfície/análise , Medula Óssea/patologia , Linhagem Celular , Ensaio de Unidades Formadoras de Colônias , Células-Tronco Hematopoéticas/patologia , Humanos , Leucemia Linfoide/imunologia , Fenótipo , Linfócitos T/imunologia , Linfócitos T/patologia
7.
Clin Nephrol ; 25 Suppl 1: S186-8, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3708930

RESUMO

A model of chronic serum sickness (CSS) was established in Wistar rats. Rats were given 2 mg of bovine serum albumin (BSA) i.p. five days/week. A group of six male rats were bred which developed albuminuria after three weeks. Rat albumin was measured by radial immuno-diffusion. Albuminuria increased gradually over the first 80 days. On days 87 and 88 rats were given 25 mg/kg methylprednisolone (MP) i.p. Albuminuria increased from 1.1 mg/ml to 1.7 mg/ml. After proteinuria had returned to pre-treatment values, MP was given again with the same result. From day 115 rats were given 25 mg/kg of CYA i.p. for three consecutive days. Albuminuria fell from 0.85 mg/ml to 0.28 mg/ml, and for the first time rats developed microscopic haematuria. After five days proteinuria returned to former levels but then rose to higher levels. On day 146 rats were given CYA and albuminuria fell from 1.7 to 0.45 mg/ml. On day 150 the renal histology was examined by light microscopy and the glomeruli showed no significant abnormalities.


Assuntos
Ciclosporinas/farmacologia , Proteinúria/urina , Doença do Soro/urina , Animais , Feminino , Rim/patologia , Masculino , Proteinúria/patologia , Ratos , Ratos Endogâmicos , Doença do Soro/patologia
8.
Aust Fam Physician ; 21(8): 1170-1, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1530498
10.
Int J Lab Hematol ; 29(5): 352-60, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17824916

RESUMO

As part of an iron absorption study, we needed to accurately count reticulocytes in the peripheral blood of healthy human volunteers before measuring their enrichment with stable iron isotopes given in an oral dose. Recent studies have suggested the usefulness of reticulocyte counting by flow cytometry, through a combination of differential light scatter and measurement of the stoichiometric binding of thiazole orange (TO) to RNA within the maturing erythrocyte. Using this method we set out to improve the precision of our quantitative analysis by counting more cells, as reticulocytes normally comprise <2% of the red cell population. To ensure exclusion of other cell types, we identified WBCs and platelets with CD16+CD45- allophycocyanin and CD61- phycoerythrin, respectively. After removal of CD16(+) CD45(+) TO(+) WBCs and CD61(+) TO(-) platelets from analysis, the remaining cells were a combination of CD61(-) TO(-) erythrocytes, CD61(-) TO(+) reticulocytes and CD61(+) TO(+) reticulated platelets. Reticulocyte counts were lower after exclusion of CD61(+) TO(+) cells from analysis. They were similarly lower when erythrocyte precursors were positively identified through their glycophorin A expression and TO uptake. We conclude that it is necessary to exclude reticulated platelets from flow cytometric reticulocyte analysis.


Assuntos
Plaquetas/citologia , Citometria de Fluxo/métodos , Contagem de Reticulócitos/métodos , Plaquetas/fisiologia , Separação Celular/métodos , Humanos , Processamento de Imagem Assistida por Computador , Contagem de Reticulócitos/instrumentação
11.
Semin Nurse Manag ; 4(4): 200-4, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9052278

RESUMO

A senior health care executive describes the strength of the Continuous Improvement philosophy in assisting senior and middle managers in transforming a children's hospital. Emphasizing the power of positive leadership in developing common goals and shared visions, and the relationship of midlevel managers to that process, examples are cited from a patient care delivery redesign project and in child advocacy.


Assuntos
Objetivos , Reestruturação Hospitalar/organização & administração , Hospitais Pediátricos/organização & administração , Liderança , Gestão da Qualidade Total/organização & administração , Criança , Defesa da Criança e do Adolescente , Humanos , Objetivos Organizacionais
12.
Artigo em Inglês | MEDLINE | ID: mdl-6657686

RESUMO

Rabbits given acute serum sickness (ASS) and treated with Cyclosporin A (CyA) developed glomerular capillary thrombosis and cortical infarction. These lesions were associated with severe endothelial injury and platelet-fibrin-leucocyte thrombi. They were not seen in untreated rabbits with ASS, nor in normal rabbits given CyA alone in equivalent doses. A similar renal lesion has been reported in patients receiving CyA following bone marrow transplantation.


Assuntos
Ciclosporinas/toxicidade , Infarto/induzido quimicamente , Córtex Renal/irrigação sanguínea , Doença do Soro/tratamento farmacológico , Animais , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Coelhos
13.
Br J Exp Pathol ; 63(6): 606-14, 1982 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7150510

RESUMO

We investigated the effect of high doses (50 mg/kg/day) of i.v. methylprednisolone ("pulses") on a model of acute serum sickness in rabbits, using bovine serum albumen as antigen and endotoxin as an adjuvant. The pulses were given on 2 consecutive days at one of the following times during antigen elimination: Days 1 and 2, Days 5 and 6, and Days 8 and 9. Methylprednisolone did not alter antibody production, or the size of circulating immune complexes. Pulses given at any period inhibited the fibrinoid necrosis associated with arteritis, but did not otherwise lessen the histopathological changes. Pulses given on Days 1 and 2 or at the end of immune elimination on Days 8 and 9 increased proteinuria and haematuria, and tended to increase histopathological changes, whereas pulses given at the onset of immune elimination on Days 5 and 6 in contrast reduced haematuria, but had a variable effect on proteinuria and organ damage. In this model high-dose steroids produced no consistent amelioration of the disease, apart from reduced fibrinoid necrosis, and at some times there was a tendency for the disease to be exacerbated.


Assuntos
Metilprednisolona/administração & dosagem , Doença do Soro/tratamento farmacológico , Animais , Formação de Anticorpos/efeitos dos fármacos , Complexo Antígeno-Anticorpo/metabolismo , Complemento C3/metabolismo , Relação Dose-Resposta a Droga , Feminino , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Injeções Intravenosas , Rim/patologia , Pulmão/patologia , Miocárdio/patologia , Coelhos , Soroalbumina Bovina/imunologia , Doença do Soro/patologia
14.
Br J Exp Pathol ; 65(6): 731-43, 1984 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-6149761

RESUMO

Rabbits given acute serum sickness (ASS) and treated with cyclosporin A (CyA) developed a severe, systemic vascular injury, which was not similar to that normally seen in ASS. Thirty-three NZW rabbits received a single intravenous injection of 250 mg/kg bovine serum albumen (BSA) with or without endotoxin (5 micrograms/kg), on day 0. Groups of rabbits were given intramuscular CyA as follows: 15 mg/kg/day from day -2 to +8, or 25 mg/kg/day from day -2 to +3 or day 0 to 5. Muscular arteries of the heart and splanchnic organs developed an arterial injury in which there was extensive fibrinoid necrosis of the vessel wall but little or none of the mononuclear cell reaction that is normally associated with the arteritis of ASS. A microvascular injury also occurred which led to interstitial haemorrhage in the gastric mucosa and multi-focal necrosis in the heart and liver. These lesions were seen with equal frequency in all groups of rabbits with serum sickness who received CyA, irrespective of whether they also received endotoxin. We suggest that CyA altered the host inflammatory response to the injury initiated by the BSA-anti-BSA immune complexes and this led to enhanced vascular injury. The inhibition by CyA of the perivascular cellular reaction suggests that this reaction may be mediated by T lymphocytes. This model should provide further insight into the pathogenesis of arteritis, as well as the mechanisms of cyclosporin toxicity.


Assuntos
Ciclosporinas/toxicidade , Poliarterite Nodosa/induzido quimicamente , Doença do Soro/tratamento farmacológico , Animais , Vasos Coronários/patologia , Feminino , Mucosa Gástrica/patologia , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/patologia , Artéria Hepática/patologia , Miocardite/induzido quimicamente , Miocardite/patologia , Poliarterite Nodosa/patologia , Coelhos , Doença do Soro/patologia
15.
Br J Exp Pathol ; 65(1): 133-44, 1984 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-6696830

RESUMO

Rabbits given acute serum sickness (ASS) and treated with cyclosporin A (CyA) developed glomerular capillary thrombosis and cortical infarction, lesions not seen in unmodified ASS. Thirty-three NZW rabbits received a single intravenous injection of 250 mg/kg bovine serum albumen (BSA) with or without endotoxin (5 micrograms/kg) on day 0. Groups of rabbits were given intramuscular CyA as follows: 15 mg/kg from day -2 to +8, or 25 mg/kg/day from day -20 to +3 or day 0 to 5. Signs of this renal injury were haematuria, transient proteinuria, glycosuria and oliguria and they occurred during the rapid phase of antigen elimination when immune complexes were being formed. Seventeen of the 33 rabbits developed glomerular capillary thrombi and 11 of 17 also had glomerular and tubular infarction. Electron microscopic examination showed that these lesions were associated with severe endothelial injury and platelet-fibrin-leucocyte thrombi. These changes were more severe in the groups given 25 mg/kg. The lesions were not seen in untreated rabbits and ASS, nor in normal rabbits given equivalent doses of CyA alone. A strikingly similar renal lesion has been seen in patients receiving CyA following bone marrow transplantation, and also in the haemolytic uraemic syndrome. The model we describe may be valuable for the study of the mechanisms of endothelial injury and thrombosis in the kidney.


Assuntos
Ciclosporinas/efeitos adversos , Nefropatias/induzido quimicamente , Doença do Soro/tratamento farmacológico , Animais , Feminino , Hematúria/tratamento farmacológico , Infarto/induzido quimicamente , Infarto/patologia , Córtex Renal/irrigação sanguínea , Nefropatias/patologia , Glomérulos Renais/ultraestrutura , Microscopia Eletrônica , Proteinúria/tratamento farmacológico , Coelhos , Trombose/induzido quimicamente , Trombose/patologia
16.
Carcinogenesis ; 25(10): 1945-52, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15155531

RESUMO

Epidemiological studies suggest that the use of NSAIDs and/or a high intake of fruit and vegetables reduce the risk of oesophageal adenocarcinoma. Since COX-2 is up-regulated in Barrett's oesophageal carcinogenesis, the protective effect of NSAIDs and natural food components might reflect COX-2 inhibition. We explored the effects of quercetin, a natural flavonoid with a potent COX-2 inhibitory activity, and two commercially available selective COX-2 inhibitors (NS-398 and nimesulide) on cell proliferation, apoptosis, PGE2 production and COX-2 mRNA expression in a human oesophageal adenocarcinoma cell line (OE33). Changes in the relative numbers of adherent and floating cells were quantified and apoptotic cells were identified using ethidium bromide and acridine orange staining under fluorescence microscopy. Flow cytometric analysis of adherent and floating cells was used to quantify apoptosis and to examine the effects of the agents on the cell cycle. After 48 h exposure at concentrations of > or =1 microM both COX-2 inhibitors and quercetin suppressed cell proliferation (P < 0.01) and increased the fraction of floating apoptotic cells. At higher concentrations (50 microM) and longer exposure (48 h) the effects of quercetin were significantly greater than those of the selective COX-2 inhibitors (P < 0.01). Cell cycle analyses showed that quercetin blocked cells in S phase, while the selective COX-2 inhibitors blocked cells in G1/S interphase. COX-2 mRNA expression was suppressed by quercetin and the synthetic COX-2 inhibitors in a time- and dose-dependent manner. Quercetin and the synthetic COX-2 inhibitors (10 microM) suppressed PGE2 production by approximately 70% after 24 h exposure (P < 0.001). We conclude that OE33 is a useful model for the study of COX-2 expression and associated phenomena in human adenocarcinoma cells. Synthetic COX-2 inhibitors and the food-borne flavonoid quercetin suppress proliferation, induce apoptosis and cell cycle block in human oesophageal adenocarcinoma cells in vitro, and future studies should assess their effects in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Neoplasias Esofágicas/patologia , Isoenzimas/antagonistas & inibidores , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Neoplasias Esofágicas/enzimologia , Humanos , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/metabolismo , Células Tumorais Cultivadas
17.
Eur J Immunol ; 21(10): 2517-22, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1680701

RESUMO

Alloantigens, unlike recall antigens, activate both CD45RA+ (naive) and CD45R0+ (memory) CD4+ cells to the same extent. These T cell subsets may therefore interact with each other in response to alloantigens on transplanted grafts. We have investigated if the ability of activated CD4+CD45RA+ and CD4+CD45R0+ T cells to produce and respond to interleukin 2 (IL2) and IL4 may be involved in this interaction. After activation, both subsets up-regulate their IL2 receptor (IL2R) and IL4R expression, yet IL4 substantially enhanced the proliferation of the CD4+CD45RA+ but not of the CD4+CD45R0+ T cell subset, while IL2 increased the proliferation of CD4+CD45R0+ but not of the CD4+CD45RA+ T cells. Significantly, the CD4+CD45RA+ T cells synthesized two- to threefold more mRNA for IL2 than the CD4+CD45R0+ subset, while the CD4+CD45R0+ T cells synthesized mRNA for IL4 and interferon-gamma exclusively. The addition of IL2 to alloactivated CD4+CD45R0+ T cells further up-regulated their production of all three lymphokine mRNA; in contrast, IL4 induced an increase in mRNA for IL2 in only the alloactivated CD4+CD45RA+ subset. The reciprocity in the ability of both these CD4+ T cells to synthesize and respond to IL2 and IL4 may provide a rationale for the regulation of lymphokine interactions in vivo. Furthermore, the synergy between these subsets in response to alloantigens, which was directly quantitated by co-culturing CD4+CD45RA+ and CD4+CD45R0+ cells together prior to activation, may potentiate the alloreactivity against transplanted grafts in vivo.


Assuntos
Antígenos CD/imunologia , Linfócitos T CD4-Positivos/imunologia , Antígenos de Histocompatibilidade/imunologia , Ativação Linfocitária , Subpopulações de Linfócitos T/imunologia , Humanos , Memória Imunológica , Técnicas In Vitro , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-2/biossíntese , Interleucina-2/genética , Interleucina-2/farmacologia , Interleucina-4/biossíntese , Interleucina-4/genética , Interleucina-4/farmacologia , Antígenos Comuns de Leucócito , RNA Mensageiro/genética , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-4 , Receptores Mitogênicos/metabolismo
18.
Clin Exp Immunol ; 119(1): 4-10, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10606958

RESUMO

In asthma, treatment with inhaled corticosteroids reduces chronic peribronchial inflammation and restores the balance within macrophage subpopulations. This study investigates whether corticosteroids can regulate monocyte differentiation in vitro and thereby influence the balance of functionally distinct macrophages. Graded doses of fluticasone propionate (FP) were added to cultures of normal peripheral blood monocytes in the presence or absence of IL-4. Cells were harvested after 7 days' culture. Double immunofluorescence studies were performed on cytospins of differentiated macrophages using the MoAbs RFD1 and RFD7 to distinguish inductive and suppressive macrophages by their respective phenotypes. Macrophage function was determined by quantifying allostimulation in a mixed leucocyte reaction and by measuring tumour necrosis factor-alpha (TNF-alpha) production. FP reduced the number of mature cells with a D1+ antigen-presenting phenotype and up-regulated the development of cells with the D1/D7+ and D7+ phenotypes. Functionally, this was associated with reduced stimulation of T cell proliferation in a mixed leucocyte reaction (MLR). Fluticasone also reversed the increase in both D1+ expression and TNF-alpha production induced by IL-4. The effect of FP persisted for 24 h after removal of FP from the culture medium. These results suggest that FP treatment of asthmatics may have a direct beneficial effect by normalizing the macrophage subset imbalance that contributes to the chronic peribronchial inflammation present in this condition.


Assuntos
Androstadienos/farmacologia , Antiasmáticos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Corticosteroides/administração & dosagem , Corticosteroides/farmacocinética , Corticosteroides/farmacologia , Androstadienos/administração & dosagem , Androstadienos/farmacocinética , Antiasmáticos/administração & dosagem , Antiasmáticos/farmacocinética , Asma/tratamento farmacológico , Asma/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Fluticasona , Humanos , Técnicas In Vitro , Ativação Linfocitária/efeitos dos fármacos , Teste de Cultura Mista de Linfócitos , Macrófagos/classificação , Fenótipo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/biossíntese , Fator de Necrose Tumoral alfa/biossíntese
19.
Clin Exp Immunol ; 52(3): 586-94, 1983 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-6347471

RESUMO

The effect of the immunosuppressive agent cyclosporin A (Cy A) on the renal injury in acute serum sickness was examined in rabbits. Serum sickness was induced in 23 untreated NZW rabbits by a single intravenous injection of bovine serum albumin (BSA) 250 mg/kg with E. coli endotoxin (5 micrograms/kg): BSA was eliminated after 8.6 +/- 0.16 days (mean +/- s.e. (mean]; proteinuria occurred in 19 (84%) and glomerular proliferation in 20 (87%) rabbits. When Cy A (15 or 25 mg/kg) was given daily by intramuscular injection, starting either 2 days before or at the time of induction of acute serum sickness, proteinuria was profoundly reduced and glomerular proliferation was inhibited. Even when rabbits were first treated with Cy A (25 mg/kg) 5 days after the induction of disease proteinuria and glomerular proliferation were similarly inhibited. When the treated animals were compared with controls there were no differences in the following: time to elimination of BSA, amount or size of circulating immune complexes, fall in serum C3 at immune elimination, or deposition of immune reactants in the glomeruli. These results show that Cy A inhibits the renal injury of acute serum sickness and indicate that T cells may play a role in mediating the nephritis in this condition.


Assuntos
Ciclosporinas/uso terapêutico , Glomerulonefrite/prevenção & controle , Doença do Soro/complicações , Doença Aguda , Animais , Formação de Anticorpos , Complexo Antígeno-Anticorpo/análise , Endotoxinas/imunologia , Escherichia coli , Feminino , Glomerulonefrite/imunologia , Proteinúria/prevenção & controle , Coelhos , Soroalbumina Bovina/imunologia , Soroalbumina Bovina/metabolismo , Doença do Soro/imunologia
20.
Cytometry ; 18(4): 209-17, 1994 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-7895527

RESUMO

We have compared CD10 antigen expression in normal fetal bone marrow with that of B-linage acute lymphoblastic leukemia (ALL). Both quantitative indirect immunofluoresence (QIFI) and direct immunofluorescence (IF) tests with Quantum beads were used to convert median fluorescence intensity (MFI) values into numbers of antigen molecules expressed per cell (AgE). Lymphoid precursors in the fetal marrow and liver expressed 3-12.5 x 10(3) CD10 molecules/cell with an upper limit of 5 x 10(4)/cell (MaxAgE). The median CD10 AgE in the different cases of acute B-lineage ALL were variable and ranged from undetectable to very high values (> 1.8 x 10(5). In 24 of the 72 cases (33%) tested with QIFI the median CD10 AgE was above the highest values seen in normal samples (> 5 x 10(4)/cell). An additional 23.6% of cases had higher median values than the normal median CD10 AgE. Next, CD10 antigen was quantitated in 78 cases during the routine multiparameter analysis of B-lineage leukemia using CD10/class II/CD34 3-color IF test or CD10/TdT 2-color IF test. The aberrant overexpression was confirmed in 43.6% of ALL cases. The CD10bright display suggested ALL diagnosis even when few cells were available for study, e.g., in early relapse and in ALL masquerading as aplastic anemia. The levels of CD10 expression were maintained in relapse. In addition, different CD10 levels were associated with the various chromosomal alterations: high CD10 levels (> 3 x 10(4)/cell) with hyperdiploidy, low CD10 levels (1.8-4 x 10(3)/cell) with the t(1;19) and undetectable levels (< 1.2 x 10(3)/cell) with the t(4;11) translocations.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Biomarcadores Tumorais/sangue , Citometria de Fluxo/métodos , Neprilisina/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Aberrações Cromossômicas/genética , Aberrações Cromossômicas/imunologia , Proteínas Fetais/análise , Humanos , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia
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