Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fatcon...Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fatcontaining vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the invasive technique, various other non-invasive techniques have been developed, such as ultrasound, computed tomography (CT), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) based methods. Among these techniques, ultrasound and CT provide only qualitative information about hepatic steatosis, whereas MRS-or MRI-based methods are able to determine even small amounts of fat accurately. These non-invasive magnetic resonance techniques have already proven their great potential, especially in longitudinal and cross-sectional studies regarding various metabolic conditions and medical treatment regimens. In this review, the most common, non-invasive MRS/MRI techniques for assessment of intrahepatic lipid content are described with their inherent advantages and limitations.展开更多
AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model.METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC...AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model.METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene.RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH ceils stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial origin(MH BCD), respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions (P＜0.01) under both high dose as well as low dose systemic 5-FC application,whereas MH tumors without transgene expression (MH naive) showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness (SuperCD>>YCD > > BCD > > > negative control) was defi ned as a result of a directin vivo comparison of all three suicide genes.CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model,thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.展开更多
In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is ...In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.展开更多
To assess the contribution to mutagenesis byhuman DNA repair defects,UV-irradiated shuttlevector plasmid,pZ189,was passed throughfibroblasts derived from xeroderma pigmentosum(XP)patients in DNA repair complementation...To assess the contribution to mutagenesis byhuman DNA repair defects,UV-irradiated shuttlevector plasmid,pZ189,was passed throughfibroblasts derived from xeroderma pigmentosum(XP)patients in DNA repair complementation groups A,Cand F.In comparison to results with DNA repairproficient human cells,UV-irradiated pZ189展开更多
The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging(MRI). Prior to apicoectomy, 11 patients with...The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging(MRI). Prior to apicoectomy, 11 patients with radiographically confirmed periapical lesions underwent dental MRI, including fat-saturated T2-weighted(T2 wFS) images, non-contrast-enhanced T1-weighted images with and without fat saturation(T1 w/T1 wFS), and contrast-enhanced fat-saturated T1-weighted(T1 wFS+C) images. Two independent observers performed structured image analysis of MRI datasets twice. A total of 15 diagnostic MRI criteria were evaluated, and histopathological results(6 granulomas and 5 cysts) were compared with MRI characteristics. Statistical analysis was performed using intraclass correlation coefficient(ICC), Cohen's kappa(κ), Mann–Whitney U-test and Fisher's exact test. Lesion identification and consecutive structured image analysis was possible on T2 wFS and T1 wFS+C MRI images. A high reproducibility was shown for MRI measurements of the maximum lesion diameter(intraobserver ICC = 0.996/0.998; interobserver ICC = 0.997), for the "peripheral rim" thickness(intraobserver ICC = 0.988/0.984; interobserver ICC = 0.970), and for all non-quantitative MRI criteria(intraobserver-κ = 0.990/0.995; interobserver-κ = 0.988). In accordance with histopathological results, six MRI criteria allowed for a clear differentiation between cysts and granulomas:(1) outer margin of lesion,(2) texture of "peripheral rim" in T1 wFS+C,(3)texture of "lesion center" in T2 wFS,(4) surrounding tissue involvement in T2 wFS,(5) surrounding tissue involvement in T1 wFS+C and(6) maximum "peripheral rim" thickness(all: P < 0.05). In conclusion, this pilot study indicates that radiation-free dental MRI enables a reliable differentiation between periapical cysts and granulomas in vivo. Thus, MRI may substantially improve treatment strategies and help to avoid unnecessary surgery in apical periodontitis.展开更多
文摘Hepatic steatosis as the most prevalent liver disorder can either be related to alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). In both conditions, hepatocytes excessively accumulate fatcontaining vacuoles within their cytoplasm, which is the key histological feature. In contrast to ALD, NAFLD is commonly associated with metabolic syndrome, obesity and insulin resistance. To determine increased liver fat content, liver biopsy is currently considered the gold standard. Besides the invasive technique, various other non-invasive techniques have been developed, such as ultrasound, computed tomography (CT), magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) based methods. Among these techniques, ultrasound and CT provide only qualitative information about hepatic steatosis, whereas MRS-or MRI-based methods are able to determine even small amounts of fat accurately. These non-invasive magnetic resonance techniques have already proven their great potential, especially in longitudinal and cross-sectional studies regarding various metabolic conditions and medical treatment regimens. In this review, the most common, non-invasive MRS/MRI techniques for assessment of intrahepatic lipid content are described with their inherent advantages and limitations.
基金Supported by grants from German Research Foundation (LA649-20-2)Federal Ministry of Education, Science, Research and Technology (Fo. 01KS9602, Fo. 01KV9532)Interdisciplinary Clinical Research Center (IZKF) Tubingen, and the fortune-program of the Medical Faculty of Eberhard-Karls-University Tubingen (F. 1281127)W.A.W. supported by a scholarship from Pinguin Foundation (Henkel KGaA)
文摘AIM: To investigate the effects of catalytically superior gene-directed enzyme prodrug therapy systems on a rat hepatoma model.METHODS: To increase hepatoma cell chemosensitivity for the prodrug 5-fluorocytosine (5-FC), we generated a chimeric bifunctional SuperCD suicide gene, a fusion of the yeast cytosine deaminase (YCD) and the yeast uracil phosphoribosyltransferase (YUPRT) gene.RESULTS: In vitro stably transduced Morris rat hepatoma cells (MH) expressing the bifunctional SuperCD suicide gene (MH SuperCD) showed a clearly marked enhancement in cell killing when incubated with 5-FC as compared with MH ceils stably expressing YCD solely (MH YCD) or the cytosine deaminase gene of bacterial origin(MH BCD), respectively. In vivo, MH SuperCD tumors implanted both subcutaneously as well as orthotopically into the livers of syngeneic ACI rats demonstrated significant tumor regressions (P＜0.01) under both high dose as well as low dose systemic 5-FC application,whereas MH tumors without transgene expression (MH naive) showed rapid progression. For the first time, an order of in vivo suicide gene effectiveness (SuperCD>>YCD > > BCD > > > negative control) was defi ned as a result of a directin vivo comparison of all three suicide genes.CONCLUSION: Bifunctional SuperCD suicide gene expression is highly effective in a rat hepatoma model,thereby significantly improving both the therapeutic index and the efficacy of hepatocellular carcinoma killing by fluorocytosine.
基金Supported by German Research Foundation(DFG)focusing on“Interplay between mononuclear and osteogenic cells during fracture healing in type 2 diabetics”,No.EH 471/2(to Ehnert S)German Research Foundation within the context of the Collaborative Research Center(CRC)1149“Danger Response,Disturbance Factors and Regenerative Potential after Acute Trauma”,No.251293561,C01(to Ignatius A and Fischer V)+1 种基金DFG in context of the CRC 1149,No.251293561,A01 and No.251293561 Z02(to Huber-Lang M)and DFG in the context of the CRC 1149,No.251293561,C07(to Kalbitz M).
文摘In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.
文摘To assess the contribution to mutagenesis byhuman DNA repair defects,UV-irradiated shuttlevector plasmid,pZ189,was passed throughfibroblasts derived from xeroderma pigmentosum(XP)patients in DNA repair complementation groups A,Cand F.In comparison to results with DNA repairproficient human cells,UV-irradiated pZ189
基金supported by a grant from the Dietmar Hopp Foundation (grant number: 23011228 grant holders: A.J. and S.H.)receive funding from a postdoctoral fellowship of the Medical Faculty of the University of Heidelberg
文摘The purpose of this pilot study was to evaluate whether periapical granulomas can be differentiated from periapical cysts in vivo by using dental magnetic resonance imaging(MRI). Prior to apicoectomy, 11 patients with radiographically confirmed periapical lesions underwent dental MRI, including fat-saturated T2-weighted(T2 wFS) images, non-contrast-enhanced T1-weighted images with and without fat saturation(T1 w/T1 wFS), and contrast-enhanced fat-saturated T1-weighted(T1 wFS+C) images. Two independent observers performed structured image analysis of MRI datasets twice. A total of 15 diagnostic MRI criteria were evaluated, and histopathological results(6 granulomas and 5 cysts) were compared with MRI characteristics. Statistical analysis was performed using intraclass correlation coefficient(ICC), Cohen's kappa(κ), Mann–Whitney U-test and Fisher's exact test. Lesion identification and consecutive structured image analysis was possible on T2 wFS and T1 wFS+C MRI images. A high reproducibility was shown for MRI measurements of the maximum lesion diameter(intraobserver ICC = 0.996/0.998; interobserver ICC = 0.997), for the "peripheral rim" thickness(intraobserver ICC = 0.988/0.984; interobserver ICC = 0.970), and for all non-quantitative MRI criteria(intraobserver-κ = 0.990/0.995; interobserver-κ = 0.988). In accordance with histopathological results, six MRI criteria allowed for a clear differentiation between cysts and granulomas:(1) outer margin of lesion,(2) texture of "peripheral rim" in T1 wFS+C,(3)texture of "lesion center" in T2 wFS,(4) surrounding tissue involvement in T2 wFS,(5) surrounding tissue involvement in T1 wFS+C and(6) maximum "peripheral rim" thickness(all: P < 0.05). In conclusion, this pilot study indicates that radiation-free dental MRI enables a reliable differentiation between periapical cysts and granulomas in vivo. Thus, MRI may substantially improve treatment strategies and help to avoid unnecessary surgery in apical periodontitis.
