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1.
Zhonghua Nei Ke Za Zhi ; 63(3): 284-290, 2024 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-38448192

RESUMO

Objective: To analyze the clinical application value of a novel magnetic navigation ultrasound (MNU) combined with digital subtraction angiography (DSA) dual-guided percutaneous transhepatic biliary drainage (PTCD) through the right hepatic duct for the treatment of malignant obstructive jaundice. Methods: Randomized controlled trial. The clinical data of 64 patients with malignant obstructive jaundice requiring PTCD through the right hepatic duct at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province People's Hospital) from December 2018 to December 2021 were retrospectively analyzed. The MNU group (n=32) underwent puncture guided by a novel domestic MNU combined with DSA, and the control group (n=32) underwent puncture guided by traditional DSA. The operation time, number of punctures, X-ray dose after biliary stenting as shown by DSA, patients' tolerance of the operation, success rate of the operation, pre- and post-operative total bilirubin, and incidence of postoperative complications were compared between the two groups. Results: The operation time of the MNU group was significantly shorter than that of the control group [(17.8±7.3) vs. (31.6±9.9) min, t=-6.35,P=0.001]; the number of punctures in the MNU group was significantly lower [(1.7±0.6) vs. (6.3±3.9) times, t=-6.59, P=0.001]; and the X-ray dose after biliary stenting as shown by DSA in the MNU group was lower than that in the control group [(132±88) vs. (746±187) mGy, t=-16.81,P<0.001]; Five patients in the control group were unable to tolerate the operation, and two stopped the operation, however all patients in the MNU group could tolerate the operation, and all completed the operation, with a success rate of 100% (32/32) in the MNU group compared to 93.8%(30/32) in the control group; the common complications of PTCD were biliary bleeding and infection, and the incidence of biliary bleeding (25.0%, 8/32) and infection (18.8%, 6/32) in the MNU group was significantly lower than that in the control group, 53.1% (17/32) and 28.1% (9/32), respectively. Conclusion: Magnetic navigation ultrasound combined with DSA dual-guided PTCD through the right biliary system for the treatment of malignant obstructive jaundice is safe and feasible.


Assuntos
Icterícia Obstrutiva , Humanos , Colangiografia , Drenagem , Ducto Hepático Comum , Icterícia Obstrutiva/cirurgia , Fígado , Fenômenos Magnéticos , Estudos Retrospectivos , Ultrassonografia de Intervenção
2.
Zhonghua Wai Ke Za Zhi ; 61(1): 7-12, 2023 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-36603877

RESUMO

With the development of modern liver surgical techniques and the progress of perioperative management,the survival rate after resection of hepatocellular carcinoma has been greatly improved,but the high recurrence and metastasis rate still limits the long-term survival after surgery. Preoperative neoadjuvant therapy has been confirmed to significantly reduce the postoperative recurrence rate and prolong survival in other types of cancer,but there has been a lack of effective systemic therapy for hepatocellular carcinoma for a long time,so the efficacy and regimen of neoadjuvant therapy for hepatocellular carcinoma are still controversial. PD-1/PD-L1 monoclonal antibody combined with anti-angiogenic targeted drugs has become a first-line regimen in systemic therapy for advanced hepatocellular carcinoma. This regimen has definite efficacy and high safety,bringing hope for neoadjuvant therapy of hepatocellular carcinoma. Recently,three clinical trials of neoadjuvant immunotherapy for hepatocellular carcinoma have been published internationally,which preliminarily suggest the efficacy and safety of neoadjuvant immunotherapy for hepatocellular carcinoma and lay a solid foundation for carrying out larger sample clinical studies in the future.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Terapia Neoadjuvante , Neoplasias Hepáticas/patologia , Imunoterapia
3.
Zhonghua Wai Ke Za Zhi ; 60(7): 688-694, 2022 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-35775262

RESUMO

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group(n=14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group(n=115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850,P=0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170,P=0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P=0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110,P=0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Hepáticas/terapia , Masculino , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 51(11): 1033-1037, 2017 Nov 06.
Artigo em Chinês | MEDLINE | ID: mdl-29136751

RESUMO

Objective: To analyze the premature death probability and cause-eliminated life expectancy of cardiovascular disease, cancer, chronic respiratory disease and diabetes in Chongqing residents in 2016 so as to provide recommendation for non-communicable diseases (NCDs) prevention and control in Chongqing. Methods: Death cases of Chongqing Municipality between January 1(st) and December 31(st), 2016 were reported through death case registry system of national center for disease prevention and control. Death cases were sorted by international classification of disease (ICD-10). Mortality rate, standardized mortality rate, constituent ratio, premature death probability, life expectancy, and cause-eliminated life expectancy of four major NCDs were analyzed. Results: A total of 218 004 death cases were reported in Chongqing, 2016, and the mortality rate was 731.73/100 000. Of them, a total of 179 637 death cases of the four major NCDs including cardiovascular disease, cancer, chronic respiratory disease and diabetes were reported, accounting for 82.40% of all death cases. The mortality rate and standardized mortality rate of four major NCDs was 602.95/100 000 and 455.82/100 000, respectively. The premature death probability of four major NCDs was 15.96%, and males (25.39%) had a higher premature death probability than females (10.78%). The premature death probability of cardiovascular disease, cancer, chronic respiratory disease, and diabetes were 6.01%, 8.32%, 2.05%, and 0.43%, respectively. Life expectancy would increase by 6.02, 3.19, 1.89, and 0.19 years, after eliminating cardiovascular disease, cancer, chronic respiratory disease and diabetes respectively. Conclusion: The premature death probability of major NCDs was high in Chongqing, and males had a higher premature death probability than females did. Intervention and health management of the population should be conducted according to different gender-based risk factors to reduce the premature death probability.


Assuntos
Expectativa de Vida , Mortalidade Prematura , Doenças não Transmissíveis/mortalidade , Adulto , Idoso , Doenças Cardiovasculares , Causas de Morte , Diabetes Mellitus , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias , Fatores de Risco
5.
Zhonghua Er Ke Za Zhi ; 54(7): 523-6, 2016 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-27412744

RESUMO

OBJECTIVE: To investigate the clinical-radiologic-pathologic features of bronchitis obliterans that complicated with bronchiolitis obliterans with organizing pneumonia (BOOP). METHOD: The clinical manifestations, characteristic imaging and pathology of a case with pediatric Mycoplasma pneumoniae pneumonia (MPP) complicated with bronchitis obliterans and BOOP were summarized and relative articles were reviewed. RESULT: A 10-year-old girl complained of recurrent paroxysmal cough and episodes of wheezing with exercise, productive of yellowish sputum, irregular fever for 1 month presented with lower breath sounds of left lower lobe and localized tubular breath sounds. Lung imaging studies showed atelectasis of the left lower lobe with proximal bronchiectasis. Follicular hyperplasia of bronchial mucosa, subsegmental bronchial obliterans and sputum bolt were detected via Fiberoptic bronchoscopy. Pathological sections of lung tissue revealed greyish yellow or red color, localized carnification, and yellowish intraluminal excretions. Microscopy displayed fiber connective tissue hyperplasia, foam cells and Masson bodies. Serologic examination detected the titer of MP-IgM antibody over 1∶160. Erythromycin, corticosteroids and broncho-alveolar lavage were applied to the patient, leading to improved condition for a certain period. However, the symptoms relapsed and surgical resection of left lung had to be carried out to achieve a convalescence eventually. No literature was found from the search results of " Bronchitis obliterans " and " cryptogenic organizing pneumonia" in the China National Knowledge Infrastructure (CNKI) and PubMed database during the period from January 1990 to January 2016. CONCLUSION: The patient who had Bronchitis obliterans complicated with BOOP suffered from persisting fever and respiratory symptoms, and showed lower breath sounds and localized tubular breath sounds. MP-IgM was positive. Lung image showed atelectasis with proximal bronchiectasis. Fiber connective tissue hyperplasia and Masson bodies were found in pathologic examinations. The patient was recovering after surgical resection of the affected side of the lung.


Assuntos
Bronquiolite Obliterante/complicações , Pneumonia em Organização Criptogênica/complicações , Brônquios/patologia , Bronquiectasia/complicações , Criança , China , Tosse , Feminino , Febre , Humanos , Pulmão , Pneumonia por Mycoplasma/complicações , Atelectasia Pulmonar/complicações , Sons Respiratórios , Escarro
6.
Climacteric ; 16(6): 700-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23394299

RESUMO

OBJECTIVE: To evaluate the effect of Wenshen Xiaozhng Tang (WXT) on ectopic endometrial growth and on angiogenesis in endometrial implants in a rat model. METHODS: Sprague-Dawley rats with endometriotic implants were randomly treated with low-dose WXT, high-dose WXT, or vehicle (negative control) for 28 days. Cell proliferation and vascular density in the lesions were assessed by immunohistochemistry. The levels of VEGF in peritoneal fluid were determined by ELISA. The mRNA expression of HIF-1α and Flk-1 in the endometriotic lesions was evaluated by real-time PCR. RESULTS: WXT treatment significantly decreased the lesion size and inhibited cell proliferation in the endometriotic lesions. Lowered vascular density and reduced mRNA expression of HIF-1α in the endometriotic lesions, associated with decreased concentration of VEGF in peritoneal fluid, were also observed in WXT-treated rats. CONCLUSIONS: These results suggest that WXT could be effective to suppress the growth of endometriosis, partially through its antiangiogenic activity.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Endometriose/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Animais , Líquido Ascítico/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Endometriose/metabolismo , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/prevenção & controle , Antígeno Nuclear de Célula em Proliferação/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética
7.
Am J Nephrol ; 18(4): 263-73, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9653828

RESUMO

Epoetin alfa is the cornerstone of anemia therapy in patients with end-stage renal disease. In addition to stimulating erythropoiesis, Epoetin alfa has been demonstrated to affect hemostasis. Such effects may be important because patients with chronic renal failure have a bleeding diathesis that is multifactorial in origin. Therefore, a computer literature search on the relationship between Epoetin alfa therapy for anemia in patients with end-stage renal disease and platelets, coagulation, coagulation inhibitors, and fibrinolysis was performed. All articles and abstracts reporting original data in the English language on Epoetin alfa and its effect on hemostasis were reviewed. The literature suggests that the effects of Epoetin alfa on the coagulation cascade are of minimal clinical importance. However, Epoetin alfa transiently increases the number of circulating platelets and improves platelet function, and these effects are associated with a return of the bleeding time towards normal.


Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Hematínicos/uso terapêutico , Hemostasia/efeitos dos fármacos , Falência Renal Crônica/sangue , Anemia/etiologia , Epoetina alfa , Fibrinólise/efeitos dos fármacos , Humanos , Falência Renal Crônica/complicações , Proteínas Recombinantes
8.
Am J Pathol ; 152(6): 1541-8, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9626058

RESUMO

The contribution of CD4 and CD8 cells to crescentic glomerulonephritis (GN) was studied in mice genetically deficient in CD4, CD8, and with combined CD4 and CD8 (CD4/CD8) deficiency. Wild-type (C57BL/6) mice developed GN with mild proliferative changes 7 days after an intravenous dose of sheep anti-mouse glomerular basement membrane globulin. Crescents were observed in 12.5 +/- 6.1% of glomeruli on day 14. On day 21, 51.5 +/- 7.3% of glomeruli were affected by crescents, and mice had marked azotemia and proteinuria. CD4 and combined CD4/CD8-deficient mice developed minimal evidence of GN. On day 21, their glomeruli showed only mild proliferative changes and crescents, azotemia, and proteinuria were absent. In contrast, CD8-deficient mice developed severe crescentic GN with three of five mice dying on day 20 with ascites and edema. The two mice surviving to day 21 had severe azotemia. Crescent development was accelerated (day 14, 51.6 +/- 2.4% of glomeruli; day 20 or 21, 62.0 +/- 4.0% of glomeruli). These studies demonstrate that CD4 cells are crucial for the development of crescentic GN in mice and that genetic absence of CD8 cells accelerates disease. They support the hypothesis that crescent formation is a manifestation of CD4-dependent (and CD8-independent) delayed type hypersensitivity in the glomerulus.


Assuntos
Doença Antimembrana Basal Glomerular/imunologia , Doença Antimembrana Basal Glomerular/patologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Animais , Nitrogênio da Ureia Sanguínea , Complemento C3/análise , Globulinas/análise , Globulinas/farmacologia , Imunoglobulinas/análise , Glomérulos Renais/química , Glomérulos Renais/patologia , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteinúria/imunologia , Linfócitos T/citologia
9.
Kidney Int ; 51(3): 926-31, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9067932

RESUMO

Despite the importance of tubulointerstitial fibrosis as a predictor of renal function in patients with primary glomerular disease, the identity of the cell(s) that is the source of interstitial collagen production remains unknown. The present study was performed to identify the site of alpha 1(III) production during the development of tubulointerstitial fibrosis. We studied a model of experimental tubulointerstitial nephritis associated with puromycin aminonucleoside (PAN) nephrosis. There was a twofold increase in renal cortical alpha 1 (III) mRNA expression coincident with the onset of tubulointerstitial myofibroblasts infiltration in rats with PAN nephrosis beginning on day 6, which increased to a fivefold difference by day 10. There were 60.8 +/- 40.3 myofibroblast/mm2 within the renal tubulointerstitium of rats with PAN nephrosis on day 6 that peaked at 240.2 +/- 11.1 myofibroblast/mm2 on day 14, which then declined to 43.7 +/- 9.8 myofibroblast/mm2 by day 21. By combining in situ hybridization with immunohistochemistry, alpha 1(III) mRNA expression was colocalized to cells that labeled for alpha-smooth muscle actin identifying them as myofibroblasts. Interestingly, the major site of alpha 1(III) mRNA expression shifted to tubuloepithelial cells with the waning of myofibroblast infiltration on day 21. To determine if PDGF-BB induced myofibroblasts to synthesize alpha 1(III) mRNA, we examined kidneys from rats that had been treated with PDGF-BB (5 mg/kg/day). alpha 1(III) mRNA expression also localized to cells that labeled for alpha-smooth muscle actin. These data demonstrate the cellular source of alpha 1(III) production within the renal tubulointerstitium following injury, and suggest that PDGF-BB may be mediating this production.


Assuntos
Colágeno/biossíntese , Colágeno/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Actinas/metabolismo , Animais , Autorradiografia , Becaplermina , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Hibridização In Situ , Nefrite Intersticial/etiologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Proto-Oncogênicas c-sis , Puromicina Aminonucleosídeo/toxicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew
10.
Kidney Int ; 50(6): 1922-7, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8943475

RESUMO

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine that has been identified in acute and chronic inflammatory conditions such as rheumatoid arthritis, sepsis, and renal allograft rejection. We investigated the glomerular expression of LIF at 30 minutes, and 3, 6, 9, 15 and 24 hours after administration of anti-GBM Ab (N = 3) by the RNase protection assay. Control rats received rabbit sera and were sacrificed at 30 minutes, and 6 and 24 hours. LIF mRNA relative to GAPDH mRNA was detected at low levels within the glomeruli of occasional control rats. However with the induction of anti-GBM Ab GN, there was a marked increase in LIF steady-state mRNA beginning at three hours which persisted through 24 hour. LIF mRNA was also detected in cultured mesangial cells stimulated with IL-1 beta, identifying this cell type as a potential glomerular source for this cytokine. To investigate the in vivo effect of LIF, Lewis rats were continuously infused with recombinant (r) human (h) LIF (approximately 0.5 ng/hr) or saline vehicle i.p. with ALZA osmotic pumps beginning at t = -24 hours (N = 8). All rats were injected with anti-GBM Ab intravenously at t = 0 (N = 16). LIF infusion decreased 24-hour urinary protein excretion by 85% (17 +/- 15 vs. 114 +/- 37 mg/day, P = 0.0001) and was associated with a 60% decrease in glomerular macrophage infiltration (0.8 +/- 0.2 vs. 2.0 +/- 0.6 ED-1 cells/glom, P = 0.0001). The administration of rhLIF did not affect the binding of the anti-GBM Ab to glomeruli. The beneficial effects of LIF were associated with a decrease in glomerular MCP-1 (56%), IL-1 (41%) and TNF (17%) steady state mRNA expression. The latter was associated with a 29% decrease in TNF-alpha protein expression within the glomerular lysate of nephritic rats administered LIF when compared with control rats. These data demonstrate a potential role for LIF in the therapy of anti-GBM Ab GN.


Assuntos
Glomerulonefrite/terapia , Inibidores do Crescimento/uso terapêutico , Interleucina-6 , Glomérulos Renais/imunologia , Linfocinas/uso terapêutico , Animais , Membrana Basal/imunologia , Células Cultivadas , Glomerulonefrite/etiologia , Inibidores do Crescimento/genética , Inibidores do Crescimento/fisiologia , Interleucina-1/genética , Fator Inibidor de Leucemia , Linfocinas/genética , Linfocinas/fisiologia , RNA Mensageiro/análise , Coelhos , Ratos , Proteínas Recombinantes/uso terapêutico , Fator de Necrose Tumoral alfa/genética
11.
Kidney Int ; 50(2): 665-71, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8840300

RESUMO

Monocyte chemoattractant protein 1 (MCP-1) is a C-C chemokine with potent monocyte chemotactic and activating properties that may contribute to glomerular macrophage infiltration in anti-GBM Ab GN. We have previously reported increased glomerular steady state expression of MCP-1 mRNA relative to GAPDH mRNA in the heterologous phase of experimental anti-GBM Ab GN. In this report, we expand upon these data by demonstrating that the increase in MCP-1 mRNA correlated with MCP-1 protein expression at 24 hours that was determined with an ELISA (2069 +/- 147 pg/mg glom lysate). This increase in MCP-1 expression was associated with glomerular monocyte/ macrophage infiltration which peaked at 24 hours (8.2 +/- 1.0 ED-1 cells/glom). The site of MCP-1 mRNA production was localized by combining immunohistochemistry with in situ hybridization. The majority of cells which expressed MCP-1 mRNA at three hours were intrinsic glomerular cells, while 55% of the cells that expressed MCP-1 mRNA at 15 hours were monocytes/macrophages. To determine if MCP-1 affected glomerular macrophage infiltration, rats with alpha-GBM Ab GN were administered a polyclonal neutralizing Ab to rat MCP-1. This resulted in a 38% decline in glomerular macrophage infiltration (3.3 +/- 0.3 vs. 1.8 +/- 0.2 ED-1 cells/glom, P = 0.0001) that was associated with a 45% reduction in urinary protein excretion (260 +/- 53 vs. 162 +/- 46 mg/d, P = 0.0001). These data demonstrate an important role for MCP-1 in the pathogenesis of glomerular macrophage infiltration in anti-GBM Ab GN.


Assuntos
Quimiocina CCL2/fisiologia , Glomerulonefrite/etiologia , Glomérulos Renais/patologia , Macrófagos/patologia , Macrófagos/fisiologia , Animais , Anticorpos/administração & dosagem , Membrana Basal/imunologia , Quimiocina CCL2/genética , Quimiotaxia/fisiologia , Expressão Gênica , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Imuno-Histoquímica , Hibridização In Situ , Glomérulos Renais/imunologia , Testes de Neutralização , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Coelhos , Ratos , Ratos Endogâmicos Lew
12.
Am J Physiol ; 269(5 Pt 1): L653-9, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7491985

RESUMO

Intratracheal injection of endotoxin [lipopolysaccharide (LPS)] in rats causes acute inflammation characterized by the emigration of neutrophils (PMNs) into the bronchoalveolar airspace. Antibody to PMN adhesion molecule CD11a inhibited LPS-initiated PMN accumulation in bronchoalveolar lavage (BAL) fluid by 32% (P < 0.001). Antibody to the endothelial CD11a counterreceptor intercellular adhesion molecule-1 (ICAM-1) inhibited LPS-initiated PMN accumulation in BAL fluid by 66% (P < 0.0001). Combined antibody blockade of ICAM-1 and the C-X-C chemokine cytokine-induced neutrophil chemoattractant (CINC) inhibited LPS-initiated PMN emigration by 80%, significantly more than antibody against either ICAM-1 or CINC alone. To study the relative contribution of alveolar macrophages and PMNs to intra-alveolar tumor necrosis factor (TNF), the LPS-induced TNF in BAL fluid was measured after depletion of circulating PMNs with a cytolytic antibody to CD18. Although the anti-CD18 antibody completely abrogated LPS-initiated PMN emigration into BAL fluid, TNF levels in BAL fluid were unaffected, suggesting that alveolar macrophages are the predominant cellular source of LPS-induced TNF production. In conclusion, 1) CD11a, ICAM-1, and CINC play major roles in the LPS-initiated emigration of PMNs into the bronchoalveolar space, and 2) the TNF that drives ICAM-1 and CINC expression is derived largely from alveolar macrophages rather than PMNs.


Assuntos
Quimiocinas CXC , Citocinas/farmacologia , Endotoxinas/farmacologia , Molécula 1 de Adesão Intercelular/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular , Antígeno-1 Associado à Função Linfocitária/fisiologia , Neutrófilos/fisiologia , Traqueia/efeitos dos fármacos , Animais , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células/efeitos dos fármacos , Movimento Celular , Fatores Quimiotáticos/metabolismo , Substâncias de Crescimento/metabolismo , Injeções , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Masculino , Neutrófilos/citologia , Ratos , Ratos Endogâmicos Lew
13.
Lab Invest ; 70(5): 631-8, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-7910873

RESUMO

BACKGROUND: Cytokines are intercellular polypeptide messengers that mediate immune and inflammatory responses. The temporal profile of interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein 1 (MCP-1) expression was examined in anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN). EXPERIMENTAL DESIGN: TIN was induced by immunization of Brown Norway rats with bovine cortical TBM, whereas control rats received ovalbumin. Whole kidney RNA was assessed with the RNase protection assay 3, 7, 8, 9, 10, 12, and 14 days after immunization. Cytokine mRNA expression was correlated with TNF-alpha bioactivity, renal intercellular adhesion molecule-1 expression, and CD18-positive leukocyte infiltration by immunohistochemistry. RESULTS: Increased IL-1 beta, TNF-alpha, and MCP-1 mRNA relative to glyceraldehyde-3-phosphate dehydrogenase appeared on day 7 when TIN involved 10 to 40% of the cortex, and peaked rapidly on day 8 when there was 60 to 80% cortical involvement (at which time 75 to 80% of the infiltrating cells were neutrophils). The increase in TNF-alpha mRNA correlated with increased bioactivity. The influx of mononuclear cells on day 8 was preceded by the expression of MCP-1 mRNA. The infiltrating leukocytes expressed the leukocyte beta 2-integrin (CD18) and were found in areas with increased intercellular adhesion molecule-1 expression. The mRNAs for IL-1 beta, TNF-alpha, and MCP-1 were undetectable by day 10 (at which time 95% of the infiltrating cells were mononuclear). An increase in IL-1 receptor antagonist mRNA paralleled those of IL-1 beta. The expression of IL-6 mRNA was similar to that for IL-1, except that it disappeared by day 9. CONCLUSIONS: There is a temporal association in the expression of IL-1 beta, TNF alpha, MCP-1, and IL-6 with the upregulation of intercellular adhesion molecule-1 and leukocyte infiltration within the tubulointerstitium in anti-TBM antibody-associated TIN. The narrow window of time through which these cytokines are expressed and the coincidence of their peak expression on day 8 suggest complex cytokine interactions in the pathogenesis of anti-TBM antibody TIN.


Assuntos
Moléculas de Adesão Celular/biossíntese , Citocinas/biossíntese , Expressão Gênica , Túbulos Renais/imunologia , Leucócitos/patologia , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , RNA Mensageiro/biossíntese , Animais , Anticorpos , Elementos Antissenso (Genética) , Sequência de Bases , Membrana Basal/imunologia , Bovinos , Primers do DNA , Regulação da Expressão Gênica , Gliceraldeído-3-Fosfato Desidrogenases/análise , Gliceraldeído-3-Fosfato Desidrogenases/biossíntese , Imunização , Molécula 1 de Adesão Intercelular , Interleucina-1/biossíntese , Córtex Renal/metabolismo , Córtex Renal/patologia , Leucócitos/metabolismo , Dados de Sequência Molecular , Nefrite Intersticial/imunologia , Reação em Cadeia da Polimerase , Sondas RNA , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos BN , Fator de Necrose Tumoral alfa/biossíntese
14.
J Clin Invest ; 93(1): 273-9, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7904269

RESUMO

The contribution of IL-1 to leukocyte infiltration in anti-glomerular basement membrane (GBM) antibody (Ab) glomerulonephritis (GN) was examined by the administration of a specific IL-1 receptor antagonist (IL-1ra). Lewis rats received anti-GBM Ab or normal rabbit serum and were treated with either 0.9% saline or 6 mg IL-1ra over a 24-h time period. Plasma IL-1ra concentration was 2,659 +/- 51 ng/ml 4 h after anti-GBM Ab and IL-1ra administration. PMN and monocyte/macrophage infiltration declined 39% (9.8 +/- 1.9 to 6.0 +/- 1.5 PMN/glomerulus, P < 0.001) and 29% (4.9 +/- 0.8 to 3.5 +/- 0.8 ED-1 cells/glomerulus, P = 0.002) with IL-1ra treatment at 4 h, respectively. Similarly, the number of glomerular cells staining for lymphocyte function-associated molecule-1 beta (CD18) declined 39% from 16.7 +/- 1.9 to 10.7 +/- 1.6 cells/glomerulus at 4 h (P = 0.0001). This was associated with a decrease in glomerular intracellular adhesion molecule-1 expression. The mean glomerular intracellular adhesion molecule-1 score in anti-GBM Ab GN rats treated with IL-1ra was less than that of rats administered anti-GBM Ab and 0.9% saline at 4 (2.0 +/- 0.2 vs 2.5 +/- 0.2, P < 0.05) and 24 (2.5 +/- 0.1 vs 3.1 +/- 0.2, P = 0.0001) h. These immunopathologic changes correlated with a 50% reduction in proteinuria from 147 +/- 34 to 75 +/- 25 mg/d (P < 0.002). Treatment with IL-1ra did not affect the steady state mRNA expression of either IL-1 beta or TNF alpha. An increase in the IL-1ra dose to 30 mg given within the initial 4 h provided no additional benefit. The decline in PMN and monocyte/macrophage infiltration of the glomerulus at 4 h was similar to that found in the initial study. Furthermore, the protective benefit of IL-1ra was abrogated by doubling the dose of the anti-GBM Ab GN, despite administering high dose IL-1ra (30 mg). In these studies, detectable IL-1ra was found in the serum of untreated anti-GBM Ab GN controls. These data suggest a positive yet limited role for IL-1ra in the therapeutic intervention of anti-GBM Ab GN.


Assuntos
Anticorpos , Glomerulonefrite/imunologia , Glomerulonefrite/terapia , Interleucina-1/fisiologia , Glomérulos Renais/imunologia , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/farmacologia , Animais , Membrana Basal/imunologia , Membrana Basal/patologia , Moléculas de Adesão Celular/análise , Feminino , Glomerulonefrite/patologia , Inflamação , Molécula 1 de Adesão Intercelular , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/biossíntese , Interleucina-1/imunologia , Glomérulos Renais/patologia , Leucócitos/imunologia , Leucócitos/patologia , RNA Mensageiro/biossíntese , Ratos , Ratos Endogâmicos Lew , Receptores de Interleucina-1/fisiologia , Sialoglicoproteínas/uso terapêutico , Fator de Necrose Tumoral alfa/biossíntese
15.
Biochem Biophys Res Commun ; 194(3): 1453-9, 1993 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-8352804

RESUMO

An unique form of rat platelet-derived growth factor A-chain (PDGF A-chain), with a novel 5' UT region, was cloned from a rat macrophage cDNA library and expressed. In the 5' UT, the homology of the 79 bp sequence adjacent to the ATG codon between rat and human was 92%; however, the homology of the remainder in the 5' UT was less than 30%. RNase mapping indicated this form was differentially expressed during development and immune glomerular injury, and that it probably arose from alternative splicing. We propose that the variant mRNAs reflect different levels of the control of PDGF A-chain expression.


Assuntos
Regulação da Expressão Gênica , Glomerulonefrite/genética , Fator de Crescimento Derivado de Plaquetas/genética , RNA Mensageiro/genética , Sequências Reguladoras de Ácido Nucleico/genética , Envelhecimento , Animais , Sequência de Bases , Escherichia coli/genética , Biblioteca Gênica , Glomerulonefrite/induzido quimicamente , Glomérulos Renais/metabolismo , Macrófagos , Dados de Sequência Molecular , Ratos , Homologia de Sequência do Ácido Nucleico , Distribuição Tecidual
16.
Biochem Biophys Res Commun ; 192(2): 452-8, 1993 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-8484757

RESUMO

Rat cytokine synthesis inhibitory factor (IL-10) was cloned. Like mouse and human IL-10 (mIL-10, hIL-10), rat IL-10 exhibits strong DNA and amino acid sequence homology to the open reading frame in the Epstein-Barr virus, BCRFI. The supernatant of COS-7 transfectants with rat IL-10 was found to inhibit the production of IFN-gamma by murine Th1 cells. A probe from the rat IL-10 was used in an RNase protection assay to demonstrate that IL-10 was expressed in LPS-stimulated rat spleen and FACS-purified OX-42-reactive peritoneal macrophages. The production of IL-10 by macrophages, as shown in the current study, suggests that IL-10 may have an autocrine function in inflammation.


Assuntos
Interleucina-10/genética , Macrófagos/metabolismo , Baço/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Clonagem Molecular , DNA , Fator Xa/metabolismo , Humanos , Interleucina-10/química , Interleucina-10/metabolismo , Lipopolissacarídeos , Dados de Sequência Molecular , Cavidade Peritoneal/citologia , Ratos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de Aminoácidos
17.
Invest Radiol ; 22(9): 728-32, 1987 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-3316110

RESUMO

Screening chronic hemodialysis patients (CHD) for acquired cystic disease of the kidneys (ACDK) and its complications (hemorrhage and neoplasm) has become accepted management. We evaluated patients on CHD as well as patients on chronic peritoneal dialysis (CPD) for ACDK. The kidneys of 80 chronic dialysis patients were examined by CT and real time sonography. Forty-four were hemodialysis and 36 were peritoneal dialysis patients. ACDK was found in more than 90% of both CHD and CPD patients who had been dialyzed longer than three years. Bilateral renal carcinoma was detected in one hemodialysis patient. Our results show that chronic peritoneal dialysis patients are also at risk for ACDK and its associated complications. A similar natural history for the development of ACDK in both forms of dialysis suggests that the same screening precautions should be instituted for chronic peritoneal dialysis patients.


Assuntos
Doenças Renais Císticas/patologia , Diálise Peritoneal , Diálise Renal , Tomografia Computadorizada por Raios X , Ultrassonografia , Carcinoma de Células Renais/patologia , Humanos , Rim/patologia , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/patologia , Diálise Peritoneal Ambulatorial Contínua , Doenças Renais Policísticas/patologia , Fatores de Risco
18.
Radiology ; 158(1): 67-8, 1986 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3940400

RESUMO

On rare occasions, excessive lipase production by functioning pancreatic acinar cell carcinoma results in subcutaneous and intraosseous fat necrosis. A patient with subcutaneous nodules and osteolytic lesions from metastatic fat necrosis associated with this malignancy is reported. Prompt recognition of the syndrome led to complete resection of the otherwise asymptomatic neoplasm of the exocrine pancreas.


Assuntos
Doenças Ósseas/etiologia , Carcinoma/complicações , Necrose Gordurosa/etiologia , Necrose/etiologia , Neoplasias Pancreáticas/complicações , Idoso , Doenças Ósseas/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Necrose Gordurosa/diagnóstico por imagem , Humanos , Masculino , Neoplasias Pancreáticas/diagnóstico por imagem , Cintilografia , Tomografia Computadorizada por Raios X
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