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Accurately Detecting The Features Of Urinary Tuberculosis And Exploring The Pathogenesis Of Different Incidence Of Renal Tuberculosis Between Cortex And Medulla By The Regulation Of IRAK-M Expression

Posted on:2016-04-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:1364330461958372Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Purpose:To accurately detect the features of urinary tuberculosis(TB)using the integration of imaging modalities and overview of timeline features.To explore the pathogenesis of different incidence of renal tuberculosis between cortex and medulla by the regulation of interleukin-1 receptor-associated kinase M(IRAK-M)expression.To explore the mechanism of immune tolerance induced by Cats-regulated Treg cells in renal tuberculosis.Materials and Methods:192 consecutive patients(98 men and 94 women)with urinary TB underwent contrast agent-enhanced KUB/IVP,CT or both.Two radiologists retrospectively and independently interpreted each image.Comparison of the presence of each finding was performed with statistical significance considered at a P value less than 0.05.By using cell culture,inhibit or knockout test in mice or in vitro,consuming effect analysis,chemotactic effect analysis,real-time PCR,western blot,enzyme linked immunosorbent assay,spectral CT scanning method,pathology analysis and so on,we explained that the immunosuppression could be mediated by IRAK-M in high concentration of PGE2.By using cell culture,inhibit or knockout test in mice or in vitro,consuming effect analysis,chemotactic effect analysis,real-time PCR,western blot,enzyme linked immunosorbent assay,flow cytometry analysis,JPM mark,pathology analysis,statistic analysis and so on,we explained tha the mechanism of immune tolerance induced by Cats-regulated Treg cells.Results:The most common finding was hydronephrosis in 79.1%of patients.The occurrence of destructive lesions increased,and that of repair lesions decreased during the recent four years.Additionally,81.4%of destructive renal lesions were identified in the medulla.The locations of the number of lesions in the dorsal medulla and the lower pole of the renal medulla were greater than those in the ventral,and in the middle and upper poles(P<0.05).With the stimulation from BCG and the high concentration of PGE2,the role of IRAK-M in the regulation of inflammatory pathways and the function of the monocyte-macrophage were observed with 1.8 times higher than normal control group in vitro.In vivo the inhibition of inflammatory pathways was mediated by IRAK-M which caused the different incidence of renal TB between cortex and medulla was observed in IRAK-M-knockout(IRAK-M-/-)mice.The related ontent of inflammation factors was 41%of the control group.The Tregs differentiation,survival,and immunosuppression in cultured cells was higher with 1.5 time than these without whether CatS deficiency or inhibition.These functions of CatS in mice by adoptively transferring in vitro prepared CatS-deficient or CatS inhibitor-treated Tregs,followed by examining the host immune tolerance and donor Tregs lifespan and immunosuppression activity.We found that the functions of Treg cells is higher with 50%.Through human peripheral blood mononuclear cells the functions of Treg cells could be improved with 40%in CatS inhibition.Conclusion:Some typical imaging features are shown in urinary TB.Lesions of renal TB are most likely to be observed in the dorsal medulla and lower pole of the renal medulla with kidney swelling.With the high concentration of PGE2,the role of IRAK-M is importment in the pathogenesis of different incidence of renal tuberculosis between cortex and medulla.CatS controls Tregs activities in regulating renal tuberculosis immune tolerance.The role of CatS and Tregs are importment in the pathogenesis of different incidence of renal tuberculosis between cortex and medulla.
Keywords/Search Tags:Urinary Tuberculosis, CT, Renal Tuberculosis, Interleukin-1 Receptor-associated Kinase M, Prostaglandin E2, Monocyte/macrophage, Cathepsin S, Regulatory T-cell, Toll-like Receptor, Immunosuppression
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