Biomedical subjects
Publications and source records attributed to L Wu.
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BACKGROUND: To define the imaging features of lymphoproliferative disorders that occur after liver transplantation. METHODS: A retrospective review of 605 liver transplantations between 1985 and 1998 showed 20 patients with posttransplantation lymphoproliferative disorders (PTLDs). All relevant clinical, imaging, and pathologic findings were reviewed. RESULTS: PTLDs occurred in 13 men and seven women (mean age = 43.3 years, age range = 18-68 years). The time to diagnosis of disease ranged from 1.5 to 51 months (mean = 14 months) posttransplantation. Cervical, thoracic, or abdominal lymphadenopathy was seen in 11 patients (55%). A complex portal mass in five patients (25%) was the second most common manifestation of PTLD, ranging in size from 5 to 12 cm. Other findings included gastrointestinal tract involvement in three patients (15%) seen as a duodenal mass and diffuse wall thickening in one patient and large bowel thickening in two patients with preexisting inflammatory bowel disease. CONCLUSION: There is a wide spectrum of findings in lymphoproliferative disorder after liver transplantation. The presence of lymphadenopathy, a portal mass, or bowel thickening indicates a need for further investigation to reach a pathologic diagnosis.
The early thymic precursor population of adult mice (low CD4 precursor) has the potential to produce T cells, B cells and dendritic cells if transferred into the appropriate inductive environment of an irradiated recipient. To assess its developmental potential in vitro, this population was isolated and cultured, alone and with various stromal cell lines. Cultured alone, these precursor cells all died rapidly. Co-culture with 3T3 fibroblasts gave good survival but no growth. Co-culture with thymic cortical epithelial cell lines induced significant proliferation after an initial 50% cell loss. However, the supernatant of these cortical epithelial cell lines caused only limited proliferation after very extensive cell death. Examination of the surface phenotype of the cultures on the cortical epithelial layer showed some changes which were compatible with very early steps of thymocyte development, but none of the features of more developed T cells were seen. A proportion of the proliferating cells developed some of the surface markers and morphology of dendritic cells. Immature myeloid cells also grew in these cultures; these appeared to derive from a small number of myeloid progenitors, possibly contaminants within the preparation, and their outgrowth required only soluble factors released by the cortical epithelial cells.
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The earliest T precursor population in the adult mouse thymus (CD4lo8-3-44+25-c-kit+) was previously shown to be lymphoid-restricted (T, B, NK) but to have a capacity to form dendritic cells (DC). This led to the concept of a lineage of lymphoid-derived DC. DC could be generated with high efficiency in culture from this low CD4 precursor, using a complex mix of cytokines, a mix that notably did not include GM-CSF, the cytokine normally used for development in culture of myeloid-derived DC. Using this new culture system we now show that the capacity to form DC extends to the pro-T precursor population (CD4-8-3-44+25+c-kit+) but is lost by the pre-T precursor stage (CD4-8-3-44-25+c-kit+), the point of T-cell antigen-receptor beta-gene rearrangement. The DC generated in the cultures resemble mature thymic DC by most markers, but differ in their lack of expression of BP-1 and CD8 alpha.
By analysing the nucleotide sequence of the SH genes of five mumps virus strains derived from the clinical specimens collected during the 1995/96 mumps epidemic in China a new genotype has been established. The circulating viruses showed divergence ranging from 0.8-4.5% at the nucleotide level and 3.5-12.3% at the amino acid level. In addition, a more rational approach has been taken in proposing genotype groupings to MuV strains.
Human alpha-1-antitrypsin (AAT), the most abundant protease inhibitor found in the blood, was expressed in rice embryonic tissue suspension cell culture. This was accomplished by cloning the codon-optimized AAT gene into a vector containing the rice RAmy3D promoter and its signal sequence. The synthetic gene incorporates codons synonymous with those found in highly expressed rice genes. Approximately 1000 stable transformed calli were produced by particle bombardment mediated transformation and were screened for high AAT expression using a porcine elastase inhibitory activity assay. The band shift assay also confirmed that rice-derived AAT is functional regarding its binding capability to the elastase substrate. Time course studies were conducted to determine the optimum, postinduction expression levels from cell culture. AAT expression equivalent to 20% of the total secreted proteins was achieved, and a purification scheme was developed that yielded active AAT with purity greater than 95%. The potential applications of purified plant-derived AAT for treatments of various AAT-deficient diseases are discussed.
Adenovirus E1A proteins stimulate transcription by RNA polymerases II and III from many promoters. The detailed mechanism of transcriptional activation (transactivation) by E1A proteins remains unclear, but genetic and biochemical results suggest that E1A products might act to stimulate the activity of cellular transcription factors. In this study, a detailed mutational analysis of the adenovirus E1B promoter was undertaken to define the DNA sequences required for proper basal transcription and E1A transactivation. Two key findings emerged: first the E1B promoter is an unusually simple RNA polymerase II promoter requiring only two sequence elements for proper regulation, the TATA box and a binding site for transcription factor Sp1; and second only mutations in the TATA box interfere with E1A-transactivation, suggesting that E1A mediates its effect on this promoter through the TATA-box transcription factor.
The observation that many chronic wounds are ischemic has spurred a series of studies evaluating the response of cells exposed to hypoxia. To date, these studies have shown largely beneficial effects from hypoxia, such as increased cellular replication and procollagen synthesis. These findings are counter-intuitive from a clinical standpoint because cellular growth and synthetic function are known to be retarded in chronic ischemic wounds. We have established an in vitro system in which human dermal fibroblasts grown chronically at 5 +/- 3 mm Hg will proliferate at a rate three times slower than those fibroblasts grown under standard culture conditions (namely an oxygen partial pressure of 150 mm Hg). No phenotypic changes are noted in chronically hypoxic cells, and the growth-retarding effects are reversible when the cells are returned to standard oxygen conditions. Competitive reverse transcription-polymerase chain reaction showed that acute exposure to hypoxia (up to 1 week) results in a 6.3-fold increase in the relative expression of transforming growth factor-beta1 messenger RNA, whereas chronic exposure to hypoxia leads to a 3.1-fold decrease in this message. Collagen production measured at both the mRNA and protein level is also decreased in the setting of chronic hypoxia. We propose that this system may be the most appropriate setting for studying the role of oxygen on dermal fibroblasts in ischemic, nonhealing wounds.
During early development of Dictyostelium discoideum, the enzyme cyclic nucleotide phosphodiesterase (PD) is produced at a low rate during the period its specific inhibitor (PDI) is being synthesized. In addition, PD gene expression is derepressed in the aggregation-deficient (Agg-), Pdi- mutant HC35. These observations suggest that the PDI might function to regulate PD gene expression, as well as modulate its activity. To explore this idea further, five new Agg-, Pdi- mutants were isolated and analyzed. All of the mutants produced high PD activity and overexpressed PD mRNA; four exhibited elevated levels of the 2400-nucleotide aggregation transcript and one overproduced the 1900-nucleotide vegetative transcript. In contrast, PD transcripts were not elevated in two Agg-, Pdi+ mutants. To determine if PDI production regulates PD expression, HC35 cells were transformed with plasmids carrying the PDI structural gene under the control of either the vegetative or aggregative PD promoter. Neither expression of PDI by the transformants nor addition of partially purified PDI to HC35 cells affected PD transcription. These results suggest that PD overexpression in the Pdi- mutants is not a direct consequence of the inability of these cells to produce inhibitor.
INTRODUCTION: We have performed TNF-alpha gene transfection in a mouse mammary cancer line and found significant antitumor effects. We hypothesize that the antitumor effects observed in this model are mediated by ICAM-1 and by the recruitment of CD4+ and CD8+ T cells. In vivo (Balb/c mice) tumor growth inhibition, treatment of established tumor and the effects of ICAM-1 and CD4+ and CD8+ T cells were evaluated. METHODS AND RESULTS: Gene transfection with highly efficient vectors resulted in secretion of large amounts of TNF-alpha (ELISA). In vivo antitumor effects were tested. The number of cells required to generate palpable tumor 7-10 days after subcutaneous injection was determined (1 x 10(6)). The same number of transfected cells were injected subcutaneously and compared to nontransfected controls. Tumors were measured blindly and size was analyzed on day 30 by the Wilcoxon rank sum test. Mean tumor size after injection of transfected cells is compared to that of controls. Control tumors reached the maximum allowable size by day 30 (4 cm(2)). On day 30 EMT6-TNF-alpha tumors were 0.48 cm(2) (p < 0.05). The effect of repeat injection (challenge was also tested. Animals were injected with transfected cells or wild-type control on day -6 and challenged with the same number of wild-type tumor cells on day 0. Significant immune protection against subsequent challenge was seen after first time injection with EMT6-TNF-alpha but not after first time EMT6 wild-type injection (1.62 vs. 4 cm(2)). Treatment of 6-day-old tumor was also evaluated. On day 30, mean tumor size in animals treated with EMT6-TNF-alpha was 0.9 cm(2) compared to 4 cm(2) for controls. In all experiments, CD8+ T cell depletion and CD4+ T cell depletion caused a reversal of TNF-alpha-induced inhibitory effects. In addition, in vivo antibody blocking of ICAM-1 in tumor growth experiments reversed antitumor effects (control 4 cm(2), TNF-alpha 0.2 cm(2) and ICAM-1 blocking 3.14 cm(2)). Using flow cytometry, MHC class I and II and ICAM-1 adhesion molecule expression of transfected tumor was tested. ICAM-I expression was significantly upregulated. MHC class II antigen expression was also increased. TNF-alpha-transfected human breast cancer was also evaluated. Three cell lines and fresh tumor were transfected to express TNF-alpha. In vitro analysis revealed ICAM-1 upregulation following transfection. Histologic analysis and immunohistochemical staining revealed TNF-alpha and ICAM-1 in transfected tumors and not in wild-type tumors. CONCLUSION: Highly significant in vivo tumor growth inhibition and immune protection after injection with TNF-alpha-transfected tumors appears to be mediated predominantly by CD8+ T cells and ICAM-1 upregulation. These findings suggest that TNF-alpha increases recruitment and adhesion of effector T cells.
OBJECTIVE: To compare the efficacy of two sputum collection techniques in patients with chronic obstructive pulmonary disease (COPD) in order to diagnose dysplasia or neoplasia. STUDY DESIGN: This was a crossover study design comparing induced sputum with sputum collected at home. One hundred seven patients with COPD were enrolled. Fifty-six were randomized to collect induced sputum first followed by sputum collection at home. Fifty-one randomly assigned patients collected the sputum in reverse order. RESULTS: The second sputum collection technique for both random assignments gave the greatest yield of adequate sputum. There was no significant difference in efficacy between the collection of the two sputum collection techniques in the presence of the learning (period) effect. CONCLUSION: Sputum collection is equally efficacious by the induced method and the home collection method. A learning effect was responsible for the increased yield of sputum abnormalities in the second collection session. Sputum collection at home may facilitate the amount of dysplasic and neoplastic bronchial epithelial changes in heavy smokers with COPD.
Interest in selenium pollution and remediation technology has escalated during the past two decades. Although not known to be essential for plants, selenium is an essential micronutrient for humans and animals, having important benefits for their nutrition. At high concentrations, however, selenium becomes toxic to animals and humans. A major selenium controversy in the 1980s emerged in California at the Kesterson National Wildlife Refuge; hence, scientists, environmental regulators, politicians, and the general public in the United States became aware of selenium's potential as an environmental contaminant. Consequently, extensive research has been conducted in the western United States, and a vast amount of financial resources have been allocated to develop management strategies and remediation technologies for reducing the impact of naturally occurring selenium on the biological environment. A plant-based technology, defined as 'phytoremediation', has received increasing recognition as a low-cost, environmentally friendly approach for managing the toxic effects of selenium. Plants have the ability to absorb and sequester selenium and to convert inorganic selenium to volatile forms of organic compounds that are released harmlessly into the atmosphere. The present review summarizes recent research findings and information about strategies on using phytoremediation systems to detoxify selenium-contaminated soils and waters in natural and agricultural ecosystems.
Compost stability and maturity are important parameters of compost quality. To date, nearly all compost characterization has been performed using samples freshly collected because sample storage can affect compost stability and maturity evaluation. However, sample preservation is sometimes necessary, especially for scientific research purposes. There is little information available on the effects of sample storage on compost stability and maturity. Samples of biosolids compost with different levels of stability and maturity were collected from four compost facilities in Florida (referred to as Register, Winslow, Sunset, and Meadow). Comparisons of CO2 evolution, seed germination rate, and water-soluble organic carbon (WSOC) were made between fresh samples with short storage at 4 degrees C for less than 1 wk and air-dried or frozen compost samples stored for 1 yr. The effects of storage (air-dry or frozen) on the measured parameters depended on compost stability and maturity and on the compost material source. Frozen storage reduced the peak CO2 evolution of Register samples by 12 to 29%, while accumulated CO2 evolution was reduced by 43 to 64% and 110 to 277% with air-dry and frozen storage, respectively. The storage effect on CO2 evolution with more stable compost was inconsistent. Storage did not affect compost phytotoxicity, except for samples from the Sunset facility. Air-drying reduced the WSOC by up to 35%, and freezing increased it by up to 34%, while both storage methods had no significant effect on samples of low WSOC. Despite all these variations, WSOC had a significant and consistent relation to CO2 evolution and seed germination rates with R2 of 0.78 and 0.57, respectively, regardless of storage methods.