Biomedical subjects

Jianping Dai

Publications and source records attributed to Jianping Dai.

9 recordsLinked to original sources

PubMed2006

Direct and indirect effects of alloantibodies link neointimal and medial remodeling in graft arteriosclerosis.

OBJECTIVE: Chronic vascular rejection, the main cause of allograft failure, is characterized by the destruction of smooth muscle cells (SMCs) in the media concomitantly with the proliferation of SMCs in the adjacent neointima. We hypothesized that alloantibodies might be responsible for these 2 opposite but coordinated events. METHODS AND RESULTS: We used the rat aortic interposition model of chronic vascular rejection. During the rejection process, a neointima composed of proliferating SMCs from the recipient developed, whereas the SMCs in the media, all of donor origin, underwent apoptosis. Alloantibody deposition was detected only in the media. Using in vitro cultures experiments, we observed that alloantibody binding to donor SMCs exerts (1) a rapid upregulation of the transcription of growth factors genes, followed by (2) the induction of apoptosis after 24 hours. The transient production of growth factors by donor SMCs in response to the binding of alloantibodies induced the proliferation of recipient SMCs in culture supernatant transfer experiments. Additional data suggest that among the repertoire of alloantibodies, those directed against major histocompatibility complex I might carry the remodeling effect. CONCLUSIONS: Our data suggest that during chronic vascular rejection, alloantibody binding to donor medial SMCs is a crucial event that links neointimal and medial remodeling.

Animals↗

PubMed2006

Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution.

Human abdominal aortic aneurysm (AAA) expansion has been linked to the presence of a mural thrombus. Here we explored the mechanism of the continual luminal renewal of this thrombus and its ability to release biological markers potentially detectable in plasma. We also explored the ability of platelet inhibition to pacify the thrombus and to limit aneurysm progression in an experimental model. Blood samples and mural thrombi were collected in 20 AAA patients. In parallel, segments of sodium dodecyl sulfate-decellularized guinea pig aorta were xenografted onto the abdominal aorta of 30 rats to induce aneurysms. Fifteen rats received abciximab treatment and fifteen received irrelevant immunoglobulins. Procoagulant activity and platelet activation markers (microparticles, sP-selectin, sGPV, sCD40L) were increased threefold to fivefold in eluates from the luminal thrombus layer compared to other layers. All these markers were increased twofold to fivefold in patients' plasma compared to matched controls (P < 0.005). In the rat model, abciximab reduced both thrombus area and aneurysmal enlargement (P < 0.05). Platelet aggregation is probably responsible for the renewal of the thrombus in AAA. The luminal thrombus released markers of platelet activation that could easily be detected in plasma. Platelet inhibition limited aortic aneurysm expansion in a rat model, providing new therapeutic perspectives in the prevention of AAA enlargement.

Abciximab↗

PubMed2005

Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response.

Recent advances indicate that, in various chronic inflammatory disorders, the activation of the immune system is triggered locally rather than in lymphoid organs. In this study, we have evaluated whether the humoral alloimmune response involved in chronic rejection is elicited within the graft. We used the rat aortic interposition model and microdissected the adventitia of the graft. Over time, the T cell infiltrate shifted toward a B helper phenotype. B lymphocyte clusters were detected and were the site of intense proliferation and apoptosis. Simultaneously, adventitial vascular endothelium acquired a high endothelial venule phenotype. Similar features were evidenced in the interstitium of chronically allografts (hearts and kidneys). Strikingly, ganocultured graft interstitial tissue was found to be the site of production of antibodies directed against donor MHC-I molecules. These findings, therefore, document the appearance of germinal centers in chronically rejected tissues. This lymphoid neogenesis implies that the graft is not only the target of the alloimmune response but also a site where this response actually develops, so as to optimize the communication between the targeted tissue and the immune effectors.

Animals↗

PubMed2005

Overexpression of transforming growth factor-beta1 stabilizes already-formed aortic aneurysms: a first approach to induction of functional healing by endovascular gene therapy.

BACKGROUND: The cell response to transforming growth factor-beta1 (TGF-beta1), a multipotent cytokine with healing potential, varies according to tissue context. We have evaluated the ability of TGF-beta1 overexpression by endovascular gene therapy to stabilize abdominal aortic aneurysms (AAAs) already injured by inflammation and proteolysis. METHODS AND RESULTS: Active TGF-beta1 overexpression was obtained in already-developed experimental AAAs in rats after endovascular delivery of an adenoviral construct encoding for a mutated form of active simian TGF-beta1 and in an explant model using human atherosclerotic AAA fragments incubated with recombinant active TGF-beta1. Transient exogenous TGF-beta1 overexpression by endovascular gene delivery was followed by induction of endogenous rat TGF-beta1. Overexpression of active TGF-beta1 in experimental AAAs was associated with diameter stabilization, preservation of medial elastin, decreased infiltration of monocyte-macrophages and T lymphocytes, and a decrease in matrix metalloproteinase-2 and -9, which was also observed in the explant model, in both thrombus and wall. In parallel with downregulation of the destructive process, active TGF-beta1 overexpression triggered endoluminal reconstruction, replacing the thrombus by a vascular smooth muscle cell-, collagen-, and elastin-rich intima. CONCLUSIONS: Local TGF-beta1 self-induction after transient exogenous overexpression reprograms dilated aortas altered by inflammation and proteolysis and restores their ability to withstand arterial pressure without further dilation. This first demonstration of stabilization of expanding AAAs by delivery of a single multipotent self-promoting gene supports the view that endovascular gene therapy should be considered for treatment of aneurysms.

Animals↗

PubMed2004

Robust unsupervised segmentation of infarct lesion from diffusion tensor MR images using multiscale statistical classification and partial volume voxel reclassification.

Manual region tracing method for segmentation of infarction lesions in images from diffusion tensor magnetic resonance imaging (DT-MRI) is usually used in clinical works, but it is time consuming. A new unsupervised method has been developed, which is a multistage procedure, involving image preprocessing, calculation of tensor field and measurement of diffusion anisotropy, segmentation of infarction volume based on adaptive multiscale statistical classification (MSSC), and partial volume voxel reclassification (PVVR). The method accounts for random noise, intensity overlapping, partial volume effect (PVE), and intensity shading artifacts, which always appear in DT-MR images. The proposed method was applied to 20 patients with clinically diagnosed brain infarction by DT-MRI scans. The accuracy and reproducibility in terms of identifying the infarction lesion have been confirmed by clinical experts. This automatic segmentation method is promising not only in detecting the location and the size of infarction lesion in stroke patient but also in quantitatively analyzing diffusion anisotropy of lesion to guide clinical diagnoses and therapy.

Algorithms↗

PubMed2003

Paracrine secretion of transforming growth factor-beta1 in aneurysm healing and stabilization with endovascular smooth muscle cell therapy.

BACKGROUND: Identification of molecular factors involved in artery wall stabilization after extracellular matrix injury elicited by inflammation and proteolysis has a major role in the development of new therapies for atherosclerosis. A study from our group demonstrated that endovascular seeding of vascular smooth muscle cells (VSMCs) promotes healing and stabilizes experimental aneurysms by downregulating matrix metalloproteinase and upregulating tissue inhibitor of metalloproteinase and collagen gene expression. We analyzed expression of transforming growth factor-beta (TGF-beta) and its receptors in experimental aneurysms treated with endovascular VSMC therapy. METHODS AND RESULTS: Aneurysms were generated in Fischer 344 rats by 14-day orthotopic implantation of a segment of guinea pig abdominal aorta (xenograft). During an endovascular repeat operation, syngeneic VSMCs were seeded in the aneurysm, always resulting in aneurysm diameter stabilization after 8 weeks, whereas diameter of control aneurysms infused with culture medium further increased. Seven days after repeat operation the intima or thrombus was separated from the aneurysmal wall in the two groups. Reverse transcriptase polymerase chain reaction with the domestic gene 18s as a standard demonstrated that aneurysm stabilization was associated with a statistically significant increase in TGF-beta(1), but not TGF-beta(2) or TGF-beta(3), messenger RNA levels in the intima. Enzyme-linked immunosorbent assay demonstrated increased TGF-beta(1) protein in the aneurysmal wall. mRNA levels of the two serine and threonine kinase TGF-beta receptors remained unchanged. CONCLUSIONS: Healing and stabilization of aneurysms with endovascular cell therapy is associated with a specific pattern of gene expression, resulting in paracrine secretion of TGF-beta(1). Our study provides insight into the molecular mechanisms of arterial aneurysm healing and stabilization.

Animals↗

PubMed2003

CT perfusion imaging and CT subtraction angiography in the diagnosis of ischemic cerebrovascular disease within 24 hours.

OBJECTIVE: To evaluate the value of the clinical use of CT perfusion imaging (CTPI) and CT subtraction angiography (CTSA) for diagnosing acute ischemic cerebrovascular disease (AICVD). METHODS: Twenty-four patients with AICVD onset within 24 hours were examined with regular CT, CTPI, and CTSA. Some cases received CTPI, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), digital subtraction angiography (DSA) or single photon emission computer tomography (SPECT) during follow-up examinations. RESULTS: Of the 24 cases, 11 had negative results from regular CT scans 3 - 6 hours after onset of stroke in 6 cases, 6 - 12 hours in 3 cases, and 12 - 24 hours in 2 cases. Ten of these cases were then confirmed by CTPI as having ischemic lesions, 2 with middle cerebral artery occlusion (MCAO), and 1 case with transient ischemic attack (TIA) with CTPI negative. Of the 24 cases, 13 had positive results from regular CT, 9 were diagnosed with ischemic lesions larger by using CTPI than regular CT, 1 case had MCAO and 1 had internal carotid artery occlusion (ICAO). There were 4 cases with ischemic lesions observed with regular CT having nearly the same range as that of lacunar infarctions using CTPI. Another 4 cases had more than 2 lesion areas. The peak time (PT), mean transit time (MTT) and relative flow (RF) of 24 cases were markedly different. The sides of ischemic lesions compared to each other and the core of the lesion compared to peripheral zones were also altered significantly (P < 0.01). CONCLUSIONS: Combined CTPI with CTSA can detect acute ischemic lesions at early and hyper-early stages and could distinguish between TIA, lacunar infarction and a larger area of infarction. Using semiquantitative blood perfusion analysis status, CTPI with CTSA could define position, area and range of the ischemic lesion and penumbra. These scans can also analyze the brain blood perfusion status. It is important to early diagnose the occlusion of the entire division of the internal carotid artery or middle cerebral artery and it is meaningful to assess prognosis and assignment of therapy.

Adult↗

PubMed2002

High prevalence of HIV-1 and hepatitis C virus coinfection among injection drug users in the southeastern region of Yunnan, China.

The southeastern region of Yunnan province is a key site for drug trafficking and HIV-1 infection spread from the west of Yunnan and Laos to southeastern China. To investigate the prevalence of HIV-1 infection and hepatitis C virus (HCV) coinfection among injection drug users (IDUs) in southeastern Yunnan, three cohorts of 285 addicts, including 242 IDUs and 43 oral drug users, living in the cities of Gejiu and Kaiyuan and the county of Yanshan were studied. HIV-1 and HCV infections were detected by enzyme-linked immunosorbent assay and/or polymerase chain reaction. Data on the age, sex, risk behavior, drug use history, employment, ethnic background, and marriage status were obtained by interview. The overall prevalence of HIV-1 infection was 71.9%. The rate of HCV coinfection among 138 HIV-1-infected IDUs was 99.3%. Most HIV-infected IDUs were 20 to 35 years old (86.7%) and were ethnic Han (75.9%), suggesting that the epidemic in Yunnan is no longer confined to non-Han ethnic minorities. HIV prevalence in female IDUs (81.2%) was significantly higher than in male IDUs (68.2%) ( p <.05). The prevalence of HIV infection reached 68.4% after 1 year of injection drug use. Needle/syringe sharing is the major high risk factor for the spread of HIV-1 and HCV infections. Large-scale educational campaigns are urgently needed to reduce the spread of HIV and HCV infection in these regions.

Adolescent↗

PubMed2002

Cerebral angiography and MR perfusion images in patients with ischemic cerebral vascular disease.

OBJECTIVE: To evaluate the value of perfusion MR imaging and angiographic evidence of collateral circulation in symptomatic patients with ischemic cerebrovascular diseases (ICVD). METHODS: Cerebral angiography and perfusion MR were performed in 16 patients with symptoms of ICVD. Qualitative perfusion maps were calculated for regional cerebral blood volume (rCBV) and mean transit time (MTT). RESULTS: A total of 27 lesions were seen on the perfusion MR maps (6 infarcts and 21 ischemic lesions) and most of them (26/27) showed a prolonged MTT. MTT is sensitive to the presence of ischemic lesions, but not sufficient in distinguishing infarct from ischemia. All of the infarcts showed a decreased rCBV, while most of the ischemic lesions showed a normal or increased rCBV. When collateral circulation was identified on angiography, most ischemic lesions were not infarcts and had a normal or increased rCBV. The absence of angiographically identifiable cerebral collaterals may not always result in an infarct; 50% had decreased rCBV. Despite the absence of angiographic collaterals, the other half had normal or increased rCBV. CONCLUSION: Cerebral angiographic evidence of collateral circulation is important in identifying a favorable outcome in patients with ICVD. However, a lesion with a normal or increased rCBV suggests a sufficient collateral circulation even without angiographic collaterals. Perfusion images may be a potentially useful adjunctive tool in the prediction of the outcome of ICVD, particularly where no apparent collateral macrocirculation is seen on CA.

Adult↗