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Biomedical subjects

L Chen

Publications and source records attributed to L Chen.

At least 19 recordsLinked to original sources

Epidemiological characteristics of diabetes mellitus and impaired glucose regulation in a Chinese adult population: the Shanghai Diabetes Studies, a cross-sectional 3-year follow-up study in Shanghai urban communities.

AIMS/HYPOTHESIS: To estimate the prevalence and incidence of diabetes mellitus and impaired glucose regulation (IGR) in a Chinese population aged 20-94 years. SUBJECTS AND METHODS: A group of 5,628 randomly selected adults, aged 20-94 years, living in the Huayang and Caoyang communities in Shanghai, China, were investigated between 1998 and 2001. During 2002-04, 2,666 subjects were followed up. All the participants underwent anthropometric measurements, blood biochemical analyses and a 75-g OGTT. RESULTS: Based on the 2000 census data of China, the age-standardised prevalences were 6.87% for diabetes and 8.53% for IGR at baseline. More than two in five cases with diabetes were undiagnosed. The age-adjusted prevalence of diabetes and IGR increased with age. The age-adjusted prevalences of hypertension, dyslipidaemia and overweight in males were significantly higher (p < 0.001) than in females. The 3-year cumulative incidence rates of diabetes and IGR were 4.96 and 11.10%, respectively. The relative risk of developing diabetes was significantly higher in subjects with IGR than in subjects with NGT (p < 0.001). CONCLUSIONS/INTERPRETATION: The prevalence and incidence rates for diabetes or IGR have increased dramatically over the last decades, especially in younger age groups. A large proportion of cases are undiagnosed. We strongly recommend that population-based diabetes screening programmes should be implemented and generalised for younger people.

Adult↗

Kinetics and mechanisms of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 reactions with OH radicals.

The kinetics and mechanism of oxidation of CF3CHFOCH3 was studied using an 11.5-dm3 environmental reaction chamber. OH radicals were produced by UV photolysis of an O3-H2O-He mixture at an initial pressure of 200 Torr in the chamber. The rate constant of the reaction of CF3CHFOCH3 with OH radicals (k1) was determined to be (1.77 +/- 0.69) x 10(-12) exp[(-720 +/- 110)/T] cm3 molecule(-1)(s-1) by means of a relative rate method at 253-328 K. The mechanism of the reaction was investigated by FT-IR spectroscopy at 298 K. CF3CHFOC(O)H, FC(O)OCH3, and COF2 were determined to be the major products. The branching ratio (k1a/k1b) for the reactions CF3CHFOCH3 + OH --> CF3CHFOCH2* + H2O (k1a) and CF3CHFOCH3 + OH --> CF3CF*OCH3 + H2O (k1b) was estimated to be 4.2:1 at 298 K from the yields of CF3CHFOC(O)H, FC(O)OCH3, and COF2. The rate constants of the reactions of CF3CHFOC(O)H (k2) and FC(O)OCH3 (k3) with OH radicals were determined to be (9.14 +/- 2.78) x 10(-13) exp[(-1190 +/- 90)/T] and (2.10 +/- 0.65) x 10(-13) exp[(-630 +/- 90)/T] cm3 molecule(-1)(s-1), respectively, by means of a relative rate method at 253-328 K. The rate constants at 298 K were as follows: k1 = (1.56 +/- 0.06) x 10-13, k2 = (1.67 +/- 0.05) x 10-14, and k3 = (2.53 +/- 0.07) x 10-14 cm3 molecule(-1)(s-1). The tropospheric lifetimes of CF3CHFOCH3, CF3CHFOC(O)H, and FC(O)OCH3 with respect to reaction with OH radicals were estimated to be 0.29, 3.2, and 1.8 years, respectively.

Journal Article↗

Functional reconstruction of maxilla with pedicled buccal fat pad flap, prefabricated titanium mesh and autologous bone grafts.

The aim of this study was to evaluate the use of pedicled buccal fat pad flap (PBFPF), prefabricated titanium mesh and autologous bone graft in maxillary reconstruction. Seventeen patients with a unilateral class I-III maxillary defect were involved. Preoperatively, a solid model was manufactured based on virtual maxillectomy and reconstruction of the abnormal maxilla. Intraoperatively, PBFPF was applied to repair the soft-tissue defect, serving as nasal lining and the receiving bed for bone grafts. Titanium mesh was prefabricated on the solid model and then, together with bone grafts from iliac crest, fixed to residual bones to reconstruct the hard-tissue defect. Postoperative aesthetic appearance and function were followed up. No exposure of titanium mesh, leakage or oronasal regurgitation occurred. Of the patients with a class I or II defect 91% (10/11) and of those with a class III defect 50% (3/6) gained a good appearance. Fifteen patients were articulate. Eleven patients received dental rehabilitation and had a normal diet. PBFPF with prefabricated titanium mesh and autologous bone grafts is a reliable option for reconstruction of unilateral maxillary defects of class I and II, but this method alone should be used cautiously in defects of class III and beyond.

Adipose Tissue↗

Photosynthetic and biochemical activities in flag leaves of a newly developed superhigh-yield hybrid rice (Oryza sativa) and its parents during the reproductive stage.

Responses of net photosynthetic rates to intercellular CO(2) concentration (P (n)/C (i) curves) and photochemical characteristics were investigated in flag leaves of newly developed superhigh-yield hybrid rice (Oryza sativa L.) LiangYouPeiJiu (LYPJ) and its maternal PeiAi64S (PA64S) and paternal WuMang9311 (WM9311) lines grown in the field during the reproductive stage. The results showed that photosynthetic functions, such as the electron transport activities of photosystems and photophosphorylation, assessed in vivo from P (n)/C (i) curves under field conditions declined more or earlier than those obtained in vitro. The degradation of polypeptides of thylakoid membranes was slower than those for P (Ca=360) (light-saturated net photosynthetic rate measured at 360 mumol mol(-1)) and CE (carboxylation efficiency, obtained from the initial slope of the P (n)/C (i) curve). The initial inhibition of the PSII electron transport and oxygen-evolving activity induced by senescence occurred before the degradation of the oxygen-evolving complex. In comparison, LYPJ had intermediate photosynthetic functions in the early stage of leaf development, but greater photochemical activities in the mid and late stages. WM9311 showed a similar pattern of changes but lower values, and PA64S had higher values in the early stage but showed a faster rate of senescence than LYPJ. These findings implied that the hybrid LYPJ demonstrated intermediate photosynthetic activities between its parents in the early stage of leaf development, whereas it had higher photosynthetic activities than its parents in the mid and late stages, which may be responsible for its high yield.

Carbon Dioxide↗

Equation-free dynamic renormalization in a glassy compaction model.

Combining dynamic renormalization with equation-free computational tools, we study the apparently asymptotically self-similar evolution of void distribution dynamics in the diffusion-deposition problem proposed by Stinchcombe and Depken [Phys. Rev. Lett. 88, 125701 (2002)]. We illustrate fixed point and dynamic approaches, forward as well as backward in time; these can be used to accelerate simulators of glassy dynamic phenomena.

Journal Article↗

Neurotensin selectively facilitates glutamatergic transmission in globus pallidus.

The tridecapeptide neurotensin has been demonstrated to modulate neurotransmission in a number of brain regions. There is evidence that neurotensin receptors exist in globus pallidus presynaptically and postsynaptically. Whole-cell patch-clamp recordings were used to investigate the modulatory effects of neurotensin on glutamate and GABA transmission in this basal ganglia nucleus in rats. Neurotensin at 1 microM significantly increased the frequency of glutamate receptor-mediated miniature excitatory postsynaptic currents. In contrast, neurotensin had no effect on GABA(A) receptor-mediated miniature inhibitory postsynaptic currents. The presynaptic facilitation of neurotensin on glutamatergic transmission could be mimicked by the C-terminal fragment, neurotensin (8-13), but not by the N-terminal fragment, neurotensin (1-8). The selective neurotensin type-1 receptor antagonist, SR48692 {2-[(1-(7-chloro-4-quinolinyl)-5-2(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino]-tricyclo(3.3.1.1.(3.7))-decan-2-carboxylic acid}, blocked this facilitatory effect of neurotensin, and which itself had no effect on miniature excitatory postsynaptic currents. The specific phospholipase C inhibitor, U73122 {1-[6-[[17beta-3-methoyyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione}, significantly inhibit neurotensin-induced facilitation on glutamate release. Taken together with the reported postsynaptic depolarization of neurotensin in globus pallidus, it is suggested that neurotensin excites the globus pallidus neurons by multiple mechanisms which may provide a rationale for further investigations into its involvement in motor disorders originating from the basal ganglia.

Anesthetics, Local↗

Expression of rice yellow mottle virus coat protein enhances virus infection in transgenic plants.

The disease caused by rice yellow mottle virus (RYMV) is a major, economically important constraint to rice production in Africa. RYMV is mechanically transmitted by a variety of agents, including insect vectors. The production of resistant rice varieties would be an important advance in the control of the disease and increase rice production in Africa. We produced transgenic plants of the Oryza sativa japonica variety, TP309, to express a RYMV coat protein gene (CP) and mutants of the CP under the control of a ubiquitin promoter. Transgenic plants expressing genes that encode wild-type CP (wt.CP), deleted CP (DeltaNLS.CP), mRNA of the CP, or antisense CP sequences of the CP gene were characterised. Eighty per cent (80%) of independent transgenic lines analysed contained CP gene sequences. Transgenic plants were challenged with RYMV and produced two types of reactions. Most of the plants expressing antisense sequences of the CP and untranslatable CP mRNA exhibited a delay in virus accumulation of up to a week, and the level of virus accumulation was reduced compared with non-transgenic TP309 plants. Transgenic plants expressing RYMV wild-type CP (wt.CP) and deleted CP (DeltaNLS.CP) accumulated the highest levels of virus particles. These results suggest that antisense CP and untranslatable CP mRNA induced moderate resistance, whereas transgenic CP enhanced virus infection.

Capsid Proteins↗

Complete nucleotide sequences of three dsRNA segments from Raphanus sativus-root cv. Yidianhong [corrected] with leaf yellow edge symptoms.

The two minor dsRNA bands, previously detected in symptomatic leaves of Raphanus sativus-root cv. Yidianhong [corrected] were subjected to further analysis. cDNA cloning and sequencing revealed that the smaller of the two dsRNA bands is actually a doublet consisting of two co-migrating dsRNA segments and the resulting three segments were designated as RasR 3, RasR 4, and RasR 5. RasR 3 was 1717 bp in length and potentially encoded a protein of about 55.3 kDa, containing all of the six conserved motifs shared by the RNA dependent RNA polymerases of members of the family Partitiviridae. RasR 4 and RasR 5, which co-migrated in the 5% polyacrylamide gel, were 1521 and 1485 bp in length and each encoded a putative protein of unknown function. Their molecular masses, as calculated from the deduced amino acid, were 38.2 and 38.8 kDa, respectively. The 5' UTRs of all three segments shared regions of high sequence similarities, but were distinct from those of the RasR 1 and RasR 2. Taken together, these results along with those described in the previous report, suggest that more than one partitivirus was co-infecting radish leaves.

5' Untranslated Regions↗

A practical Monte Carlo MU verification tool for IMRT quality assurance.

Quality assurance (QA) for intensity-modulated radiation therapy (IMRT) treatment planning and beam delivery, using ionization chamber measurements and film dosimetry in a phantom, is time consuming. The Monte Carlo method is the most accurate method for radiotherapy dose calculation. However, a major drawback of Monte Carlo dose calculation as currently implemented is its slow speed. The goal of this work is to bring the efficiency of Monte Carlo into a practical range by developing a fast Monte Carlo monitor unit (MU) verification tool for IMRT. A special estimator for dose at a point called the point detector has been used in this research. The point detector uses the next event estimation (NEE) method to calculate the photon energy fluence at a point of interest and then converts it to collision kerma by the mass energy absorption coefficient assuming the presence of transient charged particle equilibrium. The MU verification tool has been validated by comparing the calculation results with measurements. It can be used for both patient dose verification and phantom QA calculation. The dynamic leaf-sequence log file is used to rebuild the actual MLC leaf sequence in order to predict the dose actually received by the patient. Dose calculations for 20 patient plans have been performed using the point detector method. Results were compared with direct Monte Carlo simulations using EGS4/MCSIM, which is a well-benchmarked Monte Carlo code. The results between the point detector and MCSIM agreed to within 2%. A factor of 20 speedup can be achieved with the point detector method compared with direct Monte Carlo simulations.

Body Burden↗

Cadmium is acutely toxic for murine hepatocytes: effects on intracellular free Ca(2+) homeostasis.

We studied cadmium toxicity in murine hepatocytes in vitro. Cadmium effects on intracellular free Ca(2+) concentration ([Ca(2+)](i)) were assayed, using a laser scanning confocal microscope with a fluorescent probe, Fluo-3/AM. The results showed that administration of cadmium chloride (CdCl(2), 5, 10, 25 microM) resulted in a dose-dependent decrease of hepatocyte viability and an elevated aspartate aminotransferase (AST) activity in the culture medium (p<0.05 for 25 microM CdCl(2) vs. control). Significant increases of lactate dehydrogenase (LDH) activities in 10 and 25 microM CdC1(2)-exposed groups were observed (p<0.05 and p<0.01, respectively). A greatly decreased albumin content and a more malondialdehyde (MDA) formation also occurred after CdC1(2) treatment. The Ca(2+) concentrations in the culture medium of CdCl(2)-exposed hepatocytes were significantly decreased, while [Ca(2+)](i) appeared to be significantly elevated (p<0.05 or p<0.01 vs. control). We found that in Ca(2+)-containing hydroxyethyl piperazine ethanesulfonic acid-buffered salt solution (HBSS) only, CdCl(2) elicited [Ca(2+)](i) increases, which comprised an initially slow ascent and a strong elevated phase. However, in Ca(2+)-containing HBSS with addition of 2-aminoethoxydiphenyl borane (2-APB), CdCl(2) caused a mild [Ca(2+)](i) elevation in the absence of an initial rise phase. Removal of extracellular Ca(2+) showed that CdCl(2) induced an initially slow [Ca(2+)](i) rise alone without being followed by a markedly elevated phase, but in a Ca(2+)-free HBSS with addition of 2-APB, CdCl(2) failed to elicit the [Ca(2+)](i) elevation. These results suggest that abnormal Ca(2+) homeostasis due to cadmium may be an important mechanism of the development of the toxic effect in murine hepatocytes. [Ca(2+)](i) elevation in acutely cadmium-exposed hepatocytes is closely related to the extracellular Ca(2+) entry and an excessive release of Ca(2+) from intracellular stores.

Albumins↗

Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers.

To compare the survival of women with uterine papillary serous carcinoma (UPSC) and clear cell carcinoma (CC) to those with grade 3 endometrioid uterine carcinoma (G3EC). Demographic, pathologic, treatment, and survival information were obtained from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Data were analysed using Kaplan-Meier and Cox proportional hazards regression methods. Of 4180 women, 1473 had UPSC, 391 had CC, and 2316 had G3EC cancers. Uterine papillary serous carcinoma and CC patients were older (median age: 70 years and 68 vs 66 years, respectively; P<0.0001) and more likely to be black compared to G3EC (15 and 12% vs 7%; P<0.0001). A higher proportion of UPSC and CC patients had stage III-IV disease compared to G3EC patients (52 and 36% vs 29%; P<0.0001). Uterine papillary serous carcinoma, CC and G3EC patients represent 10, 3, and 15% of endometrial cancers but account for 39, 8, and 27% of cancer deaths, respectively. The 5-year disease-specific survivals for women with UPSC, CC and G3EC were 55, 68, and 77%, respectively (P<0.0001). The survival differences between UPSC, CC and G3EC persist after controlling for stage I-II (74, 82, and 86%; P<0.0001) and stage III-IV disease (33, 40, and 54; P<0.0001). On multivariate analysis, more favourable histology (G3EC), younger age, and earlier stage were independent predictors of improved survival. Women with UPSC and CC of the uterus have a significantly poorer prognosis compared to those with G3EC. These findings should be considered in the counselling, treating and designing of future trials for these high-risk patients.

Adenocarcinoma, Clear Cell↗

Enhancement of the critical current density of YBa2Cu3Ox superconductors under hydrostatic pressure.

The dependence of the critical current density Jc on hydrostatic pressure to 0.6 GPa is determined for a single 25 degrees [001]-tilt grain boundary in a bicrystalline ring of nearly optimally doped melt-textured YBa2Cu3Ox. Jc is found to increase rapidly under pressure at +20%/GPa. A new diagnostic method is introduced (pressure-induced Jc relaxation) which reveals a sizable concentration of vacant oxygen sites in the grain boundary region. Completely filling such sites with oxygen anions should lead to significant enhancements in Jc.

Journal Article↗

Investigation of MR image distortion for radiotherapy treatment planning of prostate cancer.

MR imaging based treatment planning for radiotherapy of prostate cancer is limited due to MR imaging system related geometrical distortions, especially for patients with large body sizes. On our 0.23 T open scanner equipped with the gradient distortion correction (GDC) software, the residual image distortions after the GDC were <5 mm within the central 36 cm x 36 cm area for a standard 48 cm field of view (FOV). In order to use MR imaging alone for treatment planning the effect of residual MR distortions on external patient contour determination, especially for the peripheral regions outside the 36 cm x 36 cm area, must be investigated and corrected. In this work, we performed phantom measurements to quantify MR system related residual geometric distortions after the GDC and the effective FOV. Our results show that for patients with larger lateral dimensions (>36 cm), the differences in patient external contours between distortion-free CT images and GDC-corrected MR images were 1-2 cm because of the combination of greater gradient distortion and loss of field homogeneity away from the isocentre and the uncertainties in patient setup during CT and MRI scans. The measured distortion maps were used to perform point-by-point corrections for patients with large dimensions inside the effective FOV. Using the point-by-point method, the geometrical distortion after the GDC were reduced to <3 mm for external contour determination and the effective FOV was expanded from 36 cm to 42 cm.

Humans↗

Evi1 is a survival factor which conveys resistance to both TGFbeta- and taxol-mediated cell death via PI3K/AKT.

In hematopoietic cells the transforming potential of the ecotropic viral integration site 1 (Evi1) oncogene is thought to be dependent upon the ability to inhibit TGFbeta signaling. Although Evi1 has recently been implicated in certain epithelial cancers, the effects of Evi1 on transformation and TGFbeta signaling in epithelial cells are not completely understood. Herein, we have determined the effects of Evi1 on TGFbeta signaling in intestinal epithelial cells. Stable expression of Evi1 in non-transformed intestinal epithelial cells inhibited induction of some Smad3-dependent TGFbeta target genes, such as PAI1. However, TGFbeta-mediated induction of cellular adhesion signaling components such as integrin1 and paxillin was not inhibited by Evi1; nor did Evi1 inhibit TGFbeta-mediated epithelial to mesenchymal transition. Likewise, Evi1 did not inhibit TGFbeta-mediated downregulation of cyclin D1 or block TGFbeta-mediated growth inhibition. However, Evi1 did inhibit TGFbeta-mediated apoptosis by a process that involves phosphoinositide-3-kinase (PI3K) and its downstream effector AKT. The ability of Evi1 to suppress apoptosis is not restricted to TGFbeta-mediated cell death, since Evi1 also protects intestinal epithelial cells from taxol-mediated apoptosis. Evi1 is overexpressed in some human colon cancer cell lines, and overexpression is associated with amplification of the Evi1 gene. Knockdown of Evi1 by siRNA inhibited AKT phosphorylation in HT-29 human colon cancer cells and increased their sensitivity to taxol-mediated apoptosis. These data indicate that Evi1 functions as a survival gene in intestinal epithelial cells and colon cancer cells, activating PI3K/AKT and conveying resistance to both physiological and therapeutic apoptotic stimuli.

Animals↗

Non-invasive coronary flow reserve is correlated with microvascular integrity and myocardial viability after primary angioplasty in acute myocardial infarction.

OBJECTIVE: To test whether preserved coronary flow reserve (CFR) two days after reperfused acute myocardial infarction (AMI) is associated with less microvascular dysfunction (" no-reflow" phenomenon) and is predictive of myocardial viability. DESIGN: 24 patients with anterior AMI underwent CFR assessment in the left anterior descending coronary artery (LAD) with transthoracic echocardiography and myocardial contrast echocardiography (MCE) 48 h after primary angioplasty in the LAD (mean 4 (SD 2) and 3 (1) days, respectively). Low-dose dobutamine echocardiography was performed 6 (3) days after AMI and follow-up echocardiography at three months. RESULTS: No-reflow extent was greater in patients with impaired CFR (< 2.5) than in those with preserved CFR (> 2.5) (55 (35)% v 11 (25)%, p < 0.001). MCE reflow was more common in patients with preserved CFR (8/12) than in those with reduced CFR (1/12, p < 0.05). Wall motion score index in the LAD territory (A-WMSI) was similar at the first echocardiography (2.14 (0.39) v 2.32 (0.47), NS), although it was better in patients with preserved CFR at dobutamine (1.38 (0.45) v 1.97 (0.67), p < 0.05) and follow-up echocardiography (1.36 (0.40) v 1.97 (0.64), p < 0.05). An inverse correlation was found between CFR and A-WMSI at dobutamine and follow-up echocardiography (r = -0.49, p = 0.016 and r = -0.55, p = 0.005) and between MCE and A-WMSI at dobutamine and follow-up echocardiography (r = -0.75, p < 0.001 and r = -0.75, p < 0.001). By multivariate analysis MCE reflow remained the only predictor of recovery at both dobutamine and follow-up echocardiography (odds ratio 1.06, 95% CI 1 to 1.1, p = 0.009). CONCLUSION: CFR is inversely correlated with the extent of microvascular dysfunction at MCE two days after reperfused AMI. CFR and MCE reflow early after AMI are correlated with myocardial viability at follow up.

Angioplasty, Balloon, Coronary↗

Measurement of the pubic portion of the levator ani muscle in women with unilateral defects in 3-D models from MR images.

OBJECTIVE: Develop a method to quantify the cross-sectional area of the pubic portion of the levator ani muscle, validate the method in women with unilateral muscle defects, and report preliminary findings in those women. METHOD: Multi-planar proton density magnetic resonance images of 12 women with a unilateral defect in the pubic portion of their levator ani were selected from a larger study of levator ani muscle anatomy in women with and without genital prolapse. Three-dimensional bilateral models of the levator ani were reconstructed (using 3-D Slicer, version 2.1b1) and divided into iliococcygeal and pubic portions. Muscle cross-sectional areas were calculated at four equally spaced locations perpendicular to a line drawn from the pubic origin to the visceral insertion using the I-DEAS computer modeling software. RESULTS: The cross-sectional area of the muscle on the side with the defect was smaller than the normal side at all the four locations. The average bilateral difference was up to 81% at location 1 (nearest pubic origin). Almost all of the volume difference (13.7%, P=0.0004) was attributable to a reduction in the pubic portion (24.6%, P<0.0001), not the iliococcygeal portion (P=0.64), of the muscle. CONCLUSIONS: A method was developed to quantify cross-sectional area of the pubic portion of the levator ani perpendicular to the intact muscle direction. Significant bilateral cross-sectional area differences were found between intact and defective muscles in women with a unilateral defect.

Case-Control Studies↗

Selective depletion of activated T cells by recombinant immunotoxin containing anti-CTLA-4 single-chain fragment of variable antibody and N-terminal fragment of perforin.

We constructed a novel immunotoxin, hS83P34, by fusing the fragment containing the N-terminal 34 amino acids of human perforin to the C-terminal of humanized anti-CTLA-4 single chain fragment of variable antibody. In vitro cytotoxicity assays demonstrated that CTLA-4-positive activated human T cells and 6T-CEM were sensitive to hS83P34, while CTLA-4-negative resting T cells and endothelial cell ECV-304 were resistant to hS83P34. The IC50s of hS83P34 for activated T cells and 6T-CEM were about 0.2 micromol/L and 1.0 micromol/L, there was no obvious cytotoxicity of ECV-304 as detected at 8 micromol/L of hS83P34. In tumor graft rejection models, after treatment with 1.2 mg/kg immunotoxin every day for 12 days, the transplanted tumor cells were rescued by immunotoxin. The tumor weights of grafts of the rejection control group, nonrejection control group, and test group were 0.006 +/- 0.014 g, 0.261 +/- 0.048 g, and 0.135 +/- 0.056 g, respectively. In the early 3 days posttransplantation, there were a lot of CD4- and CD8-positive T cells infiltrating into the tumor grafts of the rejection control group, while only a few T cells were detected in the tumor grafts of the test group. According to these results, we concluded that immunotoxin hS83P34 selectively depleted activated T cells in vitro as well as in vivo in an acute rejection model.

Antigens, CD↗

Modified vaccinia virus Ankara protein F1L is a novel BH3-domain-binding protein and acts together with the early viral protein E3L to block virus-associated apoptosis.

Infection with viruses often protects the infected cell against external stimuli to apoptosis. Here we explore the balance of apoptosis induction and inhibition for infection with the modified vaccinia virus Ankara (MVA), using two MVA mutants with experimentally introduced deletions. Deletion of the E3L-gene from MVA transformed the virus from an inhibitor to an inducer of apoptosis. Noxa-deficient mouse embryonic fibroblasts (MEF) were resistant to MVA-DeltaE3L-induced apoptosis. When the gene encoding F1L was deleted from MVA, apoptosis resulted that required Bak or Bax. MVA-DeltaF1L-induced apoptosis was blocked by Bcl-2. When expressed in HeLa cells, F1L blocked apoptosis induced by forced expression of the BH3-only proteins, Bim, Puma and Noxa. Finally, biosensor analysis confirmed direct binding of F1L to BH3 domains. These data describe a molecular framework of how a cell responds to MVA infection by undergoing apoptosis, and how the virus blocks apoptosis by interfering with critical steps of its signal transduction.

Amino Acid Sequence↗