Biomedical subjects

Wei Fang

Publications and source records attributed to Wei Fang.

13 recordsLinked to original sources

PubMed2026

Biomimetic mesoporous silica nanosphere ameliorate experimental autoimmune uveitis by delivering sCD83.

Autoimmune uveitis (AU) is an autoimmune disease that may lead to blindness, but there are currently no precise targeted therapies for its prevention and treatment. Dendritic cell (DC) is key cell involved in the pathogenesis of AU, and specific regulation of their state can help improve AU. In this work, mesoporous silica nanospheres were loaded with the immunomodulator soluble CD83 (sCD83) and subsequently camouflaged with dendritic cell (DC) membranes to fabricate the nanocarrier DCM@MSN/sCD83 for treating experimental autoimmune uveitis (EAU). Research results show that DCM@MSN/sCD83 effectively alleviated the symptoms of uveitis in EAU, reduced the proportion of CD4+CD25-T cell/CD4+CD25+T cell and the percentage of DC in the eyes and cervical lymph nodes. It also decreased the expression of STING in Müller cell. Furthermore, the efficacy of DCM@MSN/sCD83 was found to be primarily targeting DC, and promoted the expression of IL-10 and TGF-β1 in DC by activating the phosphorylated HIF/STAT3 pathway, to induce the production of CD4+CD25+ T. This effect is superior to nanomedicine loaded with dexamethasone. Moreover，DCM enabled the nanocarriers to efficiently cross the blood-eye barrier and reach cervical lymph nodes, thereby regulating peripheral immunity. This research indicate that cell membrane-modified nanoparticles targeting homologous cells can effectively improve treatment efficiency and duration, which is potential therapy strategy for uveitis.

Animals↗

PubMed2005

Acute panmyelosis with myelofibrosis: an entity distinct from acute megakaryoblastic leukemia.

The WHO criteria for diagnosing acute panmyelosis with myelofibrosis are somewhat distinct from those for acute megakaryoblastic leukemia. However, clinical and hematopathologic findings partially overlap. This has raised questions as to whether these are indeed separate, definable entities. To determine the potential importance of bone marrow biopsy supplemented by immunohistochemistry in distinguishing between these two conditions, we studied 17 bone marrow biopsies of well-characterized cases of acute panmyelosis with myelofibrosis (six cases) and acute megakaryoblastic leukemia (11 cases). We compared blast frequency, reticulin content, CD34 expression, and the degree of megakaryocytic differentiation of the blast cells in these two conditions. Our results demonstrate important differences. Acute panmyelosis with myelofibrosis is characterized by a multilineage myeloid proliferation with a less numerous population of blasts than acute megakaryoblastic leukemia (P<0.01). In the former condition, blasts are always positive with CD34, while in acute megakaryoblastic leukemia they express CD34 in 60% of the cases. The blasts in acute panmyelosis with myelofibrosis only rarely express megakaryocytic antigens. By contrast, acute megakaryoblastic leukemia has a significantly higher proportion of blasts expressing megakaryocytic antigens (P<0.01 with CD42b). Our results confirm that histology supplemented by immunohistochemistry permits the distinction of these conditions in routinely processed bone marrow biopsies.

Acute Disease↗

PubMed2004

Chaotic microlasers based on dynamical localization.

We report the direct observation of lasing action from a dynamically localized mode in a microdisk resonator with rough boundary. In contrast to microlasers based on stable ray trajectories, the performance of our device is robust with respect to the boundary roughness and corresponding ray chaos, taking advantage of Anderson localization in angular momentum. The resonator design, although demonstrated here in GaAs-InAs microdisk laser, should be applicable to any lasers and sensors based on semiconductor or polymer materials.

Journal Article↗

PubMed2004

Fatal acute lymphoblastic leukemia in mice transgenic for B cell-restricted bcl-xL and c-myc.

Expression of the c-myc gene is frequently dysregulated in malignant tumors and translocations of c-myc into the Ig H chain locus are associated with Burkitt's-type lymphoma. There is indirect evidence that bcl-x, an anti-apoptotic member of the bcl-2 gene family, may also contribute to a variety of B lymphoid tumors. In this study, we show that mice transgenic for both B cell-restricted c-myc and bcl-x(L) developed aggressive, acute leukemias expressing early B lineage and stem cell surface markers. Of interest, the tumor cells proliferated and differentiated down the B cell developmental pathway following in vitro treatment with IL-7. Analysis of sorted leukemic cells from spleen indicated constitutive expression of sterile micro and kappa transcripts in combination with evidence for D-J(H) DNA rearrangements. Several B cell-specific genes were either not expressed or were expressed at low levels in primary tumor cells and were induced following culture with IL-7. IL-7 also increased V-Jkappa and V-DJ(H) rearrangements. These data demonstrate oncogenic synergy between c-myc and bcl-x(L) in a new mouse model for acute lymphoblastic leukemia. Tumors in these animals target an early stage in B cell development characterized by the expression of both B lineage and stem cell genes.

Animals↗

PubMed2004

Long-term prognostic value of exercise 99mTc-MIBI SPET myocardial perfusion imaging in patients after percutaneous coronary intervention.

The purpose of this study was to evaluate the long-term prognostic value of exercise technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission tomography (SPET) imaging in patients after percutaneous coronary intervention (PCI). Three hundred and eighteen consecutive post-PCI patients who underwent exercise and rest (99m)Tc-MIBI SPET myocardial perfusion imaging (MPI) were followed up for 38+/-27 months. Patients with early revascularisation (<3 months after MPI) were excluded. A semiquantitative visual analysis employing a 20-segment and four-point scoring system was used to define the summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS). Death and non-fatal myocardial infarction (MI) were considered as hard events, and late revascularisation procedures (>/=3 months after MPI) as soft events. Fifty-one patients (16.0%) suffered from cardiac events during follow-up, including 1 (0.3%) death, 13 (4.1%) non-fatal MIs, 9 (2.8%) coronary artery bypass grafting procedures and 28 (8.8%) PCIs. According to the SPET results, patients were classified into three groups: patients with normal MPI (SSS=0, n=153), patients with irreversible defects (SDS<3 and SRS>1, n=100) and patients with reversible defects (SDS>/=3, n=65). The annual hard cardiac event rate in patients with reversible defects was 3.9%, which was significantly higher than that in patients with normal MPI (0.2%, chi(2)=7.71; P<0.01). The annual soft cardiac event rate in patients with reversible defects was 10.7%, which was significantly higher than that in patients with irreversible defects (2.5% chi(2)=17.69; P<0.001), and also significantly higher than that in patients with normal MPI (1.5%, chi(2)=33.89; P<0.001). In patients with normal and reversible defects, there was no significant difference in soft and hard cardiac event rates according to whether patients were symptomatic or asymptomatic ( P>0.05). However, the annual soft event rate in patients with irreversible defects and symptoms was 5.0%, which was higher than that of 0.6% in asymptomatic patients (chi(2)=6.11, P<0.05). Multivariate Cox analysis showed that SSS was the best independent predictor for hard cardiac events (chi(2)=12.70; P<0.001) and SDS was the strongest independent predictor for soft cardiac events (chi(2)=11.72; P<0.001). Post-PCI patients who have normal exercise (99m)Tc-MIBI SPET MPI have a good long-term prognosis, while those with reversible defects are at a higher risk for future cardiac events, without correlation to the chest pain symptoms. However, symptomatic patients with irreversible defects have a higher risk for repeat revascularisation, but not for hard events, compared with asymptomatic patients. Exercise (99m)Tc-MIBI SPET MPI has important clinical value for risk stratification and management decision-making in post-PCI patients.

Angioplasty, Balloon, Coronary↗

PubMed2004

Morphological changes of the peritoneum in peritoneal dialysis patients.

BACKGROUND: Long-term peritoneal dialysis (PD) requires that the peritoneal membrane remain effective for dialysis. Research directed toward human peritoneal morphology and structure is limited. The present study was performed to investigate morphological changes of the human peritoneal membrane during PD and to elucidate the possible mechanisms of its functional deterioration. METHODS: A total of 32 peritoneal biopsies were performed in normal subjects (n = 10), uremic nondialysis patients (n = 12) at the time of catheter insertion, and PD patients (n = 10) at the time of catheter removal or reinsertion or at the time of renal transplantation. Peritoneal morphology was examined by light microscopy, scanning electron microscopy, and transmission electron microscopy. RESULTS: The peritoneal membrane in normal subjects consisted of a monolayer of mesothelial cells on a basement membrane and a layer of connective tissue containing cells, blood vessels, and lymphatic vessels. Mesothelial cells were polygonal, often elongated, and had numerous microvilli on their luminal surface. There were lots of oval or roundish pinocytotic vesicles in the cytoplasm of the mesothelial cells. The peritoneal morphology of uremic nondialysis patients was similar to that of normal subjects. However, significant abnormalities of the peritoneal membrane were observed in PD patients, and the changes were found to be progressive. Microvilli were the first site of damage which involved microvilli shortening, a gradual reduction in their number, and, eventually, the total disappearance of microvilli. Mesothelial cells then detached from the basement membrane, disappearing completely in some cases. In the end, the peritoneal membrane consisted only of submesothelial connective tissue without any cells. CONCLUSIONS: PD can modify peritoneal morphology and structure. The morphological change is progressive and may be one of the important causes of peritoneal failure. Peritoneal biopsies can provide lots of valuable information about the effects of PD. Studying the relationship between peritoneal structure and its function proved very useful for understanding the physiopathology of the peritoneum during PD.

Adult↗

PubMed2003

Determination of simvastatin-derived HMG-CoA reductase inhibitors in biomatrices using an automated enzyme inhibition assay with radioactivity detection.

A robust, automated enzyme inhibition assay method was developed and validated for the determination of HMG-CoA reductase inhibitory activities in plasma and urine samples following simvastatin (SV) administration. The assay was performed on Tecan Genesis 150 and 200 systems equipped with 8-probe and 96-well plates. Plasma samples containing HMG-CoA reductase inhibitors were treated with acetonitrile for protein precipitation before being incubated with HMG-CoA reductase, [14C]-HMG-CoA, and NADPH for a fixed length of time at a fixed temperature. The product, [14C]-mevalonic acid, was lactonized and separated from excess substrate via a small ion exchange resin column, and radioactivity was counted on a scintillation counter. HMG-CoA reductase inhibitors were measured before and after base hydrolysis. The two values obtained for each sample are referred to as 'active' and 'total' HMG-CoA reductase inhibitor concentrations. Simvastatin acid (SVA), the beta-hydroxy acid of SV, was used as a standard to generate a calibration curve of HMG-CoA reductase activity versus SVA concentration (ng/ml). Three calibration ranges, 0.4-20, 2-50, and 50, 100 ng/ml, in human and animal plasma and urine were validated. The assay precision was less than 8.5%, CV in plasma and less than 10.4% in urine. The assay accuracy was 93.6-103.0 and 98.1-103.9% for the 0.4 20 and 2-50 ng/ml calibration ranges, respectively, in human plasma, and was 97.3-105.1, 94.4- 105.2, and 90.2-95.7%, for calibration range 5-100 ng/ml in rat plasma, dog plasma and human urine, respectively.

Animals↗

PubMed2003

Assay methodology for the quantitation of unbound ertapenem, a new carbapenem antibiotic, in human plasma.

Ertapenem is a new once-a-day antibiotic with excellent coverage of common community gram negative and gram positive aerobes and anaerobes. It demonstrates nonlinear protein binding in human plasma (about 94% bound). An assay for unbound drug was developed to study the pharmacokinetics of unbound ertapenem in plasma. Unbound drug is separated from plasma samples (1.0 ml) by ultrafiltration using a Centrifree((R)) centrifugal filter device. Ertapenem (vulnerable to hydrolysis of the beta-lactam moiety) is stabilized in the filtrate by adding an equal volume of 0.1 M MES buffer, pH 6.5 and then is analyzed by reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) absorbance detection (300 nm). Non-specific binding to the Centrifree((R)) device is <3%. A suitable internal standard is not available. The assay is specific and linear over the concentration range of 0.25 to 100 microgram/ml in plasma filtrate. The lower limit of quantitation (LLOQ) is 0.25 microgram/ml. Intra-day precision is C.V.<10% and accuracy ranges from 97 to 101% of nominal concentration. Inter-day precision and accuracy were determined using quality control samples (QCs) prepared in plasma ultrafiltrate at 0.5, 12 and 80 microgram/ml and stored at -70 degrees C with stabilizer. Inter-day assay accuracy and precision ranged from 100 to 111% of nominal concentration and 1.8 to 5.3% C.V. (n=40), respectively. The assay has been used to analyze plasma samples from subjects receiving 500 and 2000 mg i.v. doses of ertapenem (30 min infusion).

Anti-Bacterial Agents↗

PubMed2003

Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas.

BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis. MATERIAL: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay. RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4 malignant specimens exhibited RIZ1 promoter hypermethylation. CONCLUSION: Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene may cause parathyroid tumorigenesis via a mechanism in which genetic alteration of the MEN1 gene is redundant.

Adolescent↗

PubMed2003

[Evaluation of thrombolytic therapy by pulmonary radionuclide perfusion imaging in patients with acute pulmonary thromboembolism].

OBJECTIVE: To assess the change of pulmonary perfusion after thrombolytic therapy in patients with acute pulmonary embolism. METHODS: Eighty patients with acute pulmonary embolism received pulmonary radionuclide perfusion imaging before and after thrombolytic therapy. Percentage of perfusion defect scores (PPDs) was calculated by semiquantitative analysis of pulmonary perfusion imaging before thrombolytic therapy (PPDsD(0)), 1 - 5 days (PPDsD(5)), 6 - 30 days (PPDsD(30)) and 3 months after thrombolytic therapy (PPDsM(3)). RESULTS: The mean PPDsD(0) of the 80 patients was (57.3 +/- 16.4)%. In 64 of the 80 patients, mean PPDsD(0) and PPDsD(5) were (55.5 +/- 16.8)% and (40.0 +/- 18.6)% respectively (P < 0.001). In 30 of these 64 patients, mean PPDsD(0), PPDsD(5) and PPDsD(30) were (57.5 +/- 16.1)%, (39.3 +/- 16.8)% and (29.5 +/- 17.3)% respectively. Differences between these 3 mean PPDs values were highly significant (all P < 0.001). In 11 of the 80 patients, mean PPDsD(30) and PPDsM(3) were (40.9 +/- 18.1)% and (29.1 +/- 27.1)% respectively (P < 0.05). In two groups of patients with the courses of disease in 7 days and in 8 - 14 days respectively, significant differences were found between PPDsD(0) and PPDsD(5) (P < 0.001, P < 0.001 respectively), and between PPDsD(0) and PPDsD(30) (P < 0.001, P < 0.005 respectively). The difference was also significant, although to a lesser degree (P < 0.05) between these values in a group of patients with the course of disease beyond 14 days. CONCLUSION: This study suggests that radionuclide pulmonary perfusion imaging is a reliable method for evaluating the changes of pulmonary perfusion before and after thrombolytic therapy in patients with acute pulmonary embolism.

Acute Disease↗

PubMed2003

Expression of aquaporin-1 in the human peritoneum and the effect of peritoneal dialysis on its expression.

OBJECTIVE: To investigate the expression of aquaporin-1 (AQP1) in the human peritoneum and to evaluate the effect of peritoneal dialysis (PD) on its expression. METHODS: Peritoneal biopsies were obtained from normal subjects (n = 10), uremic nondialysis patients (n = 12) at catheter insertion and PD patients (n = 10) at the time of catheter removal, reinsertion or renal transplantation. Western blot, immuno-histochemical staining and reverse transcript-polymerase chain reaction (RT-PCR) techniques were used to investigate AQP1 expression. RESULTS: All peritoneal samples expressed AQP1 at both mRNA and protein levels. Western blot revealed a major band at 28 kD as well as more diffuse bands between 35 and 50 kD. The 28 kD band represents the nonglycosylated form of the protein while the 35 - 50 kD bands correspond to glycosylated AQP1. Immunohistochemical staining found the positive deposits were distributed in the mesothelial cells, endothelial cells of capillaries, venules and small veins, whereas no signal was detected in the arterioles. Semi-quantitative analysis showed that AQP1 expression was remarkably stable in all samples, whatever their origin (P > 0.05). CONCLUSIONS: Our findings suggested that AQP1 is the molecular counterpart of an ultra small pore during PD. Secondly, the peritoneal mesothelial cell might also be involved in peritoneal transcellular water transport. As regards whether or not the structural or distributional alterations of AQP1 in the peritoneum may be more obviously expressed during PD, further study is needed.

Adult↗

PubMed2002

Robotic inhibition assay for determination of HMG-CoA reductase inhibitors in human plasma.

The cholesterol-lowering drug simvastatin (SIMV, Zocor reduced heart attacks by 42% in patients who had high cholesterol levels and suffered from heart disease. Upon oral administration, SIMV is quickly hydrolyzed to its beta-hydroxyacid and other acid metabolites, which are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. A Tecan-based enzyme inhibition assay has been developed to improve the existing Zymark-based assay for the determination of both active and total concentrations of HMG-CoA reductase inhibitors in human plasma. A Tecan Genesis 200 robotic workstation equipped with eight probes and customized hardware was utilized to achieve higher sample throughput and improve assay reproducibility and mechanical stability. The developed enzyme inhibition assay was validated over two concentration ranges of 0.4-20 ng equivalent/mL, and 2-50 ng equivalent/mL. Intra- and interday precision data (coefficient of variation (CV)) for both concentration ranges were less than 9%, with an accuracy of 93-107%. The interday precision for the determination of quality control (QC) samples was less than 2% and 8%, respectively. The respective interday QC accuracy values were 93-103% and 97-104%. Good linearity across the two concentration ranges was observed, with acceptable reproducibility. This improved enzyme inhibition assay has been utilized to analyze human plasma samples from several clinical studies.

Humans↗

PubMed2002

[Evaluation of the relationship between deep venous thrombosis and pulmonary embolism with radionuclide techniques].

OBJECTIVE: The purpose of this study was to evaluate the relation between deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE) by radionuclide imaging. METHODS: One hundred forty patients with PTE from September 1997 to March 2001 at this institution was confirmed by clinical manifestation, pulmonary perfusion (PPI)/ventilation scan (PPV) and deep venous radionuclide venography (RNV), which were performed in all patients. There were 79 males and 61 females, with an average age of 39 +/- 18 years. Twenty-six cases underwent pulmonary angiography; 11 underwent X Ray venography of lower extremities (XRV); 18 underwent impedence plethymography (IPG); and 36 underwent lower limb echocardiography (UCG). RESULTS: Of the 140 patients with PTE, 120 (85.7%) had lower limb venous pathological changes. Among them, 94 patients had risk factors for DVT. The agreement rates of RNV with XRV, UCG and IPG were 90.9%, 72.2% and 80.0%, respectively. CONCLUSIONS: The results indicated that DVT was highly prevalent in patients with acute pulmonary embolism. Thrombosis was a primary pathogenic factor for PTE, and thrombi were mostly from proximal veins. (99m)TC-MAA radionuclide imaging was a useful method for noninvasive detection of DVT and PTE.

Adult↗