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Biomedical subjects

B J Chen

Publications and source records attributed to B J Chen.

At least 19 recordsLinked to original sources

Selective elimination of alloreactivity from immunotherapeutic T cells by photodynamic cell purging and memory T-cell sorting.

Allogeneic stem cell transplantation (alloSCT), especially in the mismatched setting, carries a high risk of life-threatening GvHD because of activation of donor T cells by Ag present on host cells. Removal of mature donor T cells can prevent GvHD but leads to delayed immune reconstitution, and an increased incidence of opportunistic infections and disease relapse. These findings demonstrate the vital role of donor T cells in providing graft-versus-tumor (GvT) and anti-pathogen effects as well as facilitating immune reconstitution. It has been well documented that GvHD can be separated from GvT effects, making it possible potentially to eliminate GvHD while preserving the immunotherapeutic benefits of donor T cells. Over the past decade, major attempts have been made to reduce GvHD incidence without loss of GvT effect, especially in the haplo-identical setting. Novel techniques to deplete host-reactive donor T cells selectively have been explored. This review focuses on the use of the photodynamic cell purging (PDP) process and of sorting memory T cells for the selective elimination of alloreactivity. Minimizing the threat of GvHD while maximizing the beneficial GvT effect would broaden the scope and effectiveness of alloSCT.

Cell Separation↗

A survey of microbial contamination of food contact surfaces at broiler slaughter plants in Taiwan.

Microbial contamination levels at broiler slaughter plants were investigated at three major slaughter plants in Taiwan during the summer and winter. The microbial contamination levels in chicken carcasses and on food contact surfaces were examined using the swab method. The results indicated that the bacterial counts were affected by the slaughter processing plant, processes, and season (P < 0.05). The bacterial counts on food contact surfaces of the equipment before operation were not significantly lower than those after processing. Regardless of the bacterial type, bacterial counts of chicken carcasses generally decreased from the scalding step to the washing step before evisceration and then increased. The cleaning procedures for food contact surfaces should be evaluated, and special attention should be given to utensils used during processing, such as gloves, baskets, and hand tools.

Abattoirs↗

T-Cell recovery in adults and children following umbilical cord blood transplantation.

T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated within the thymus and identify new thymic emigrants and those that have not divided. We measured quantitative and qualitative immunologic reconstitution and sjTREC levels in adult and pediatric recipients of umbilical cord blood transplants (UCBTs). sjTRECs were detected at normal levels in all children, starting 12 months after transplantation. sjTRECs were not detected until 18 months after transplantation in adults, and then only at a 3-fold lower level than expected for age. We used complementarity-determining region 3 (CDR3) spectratyping to measure changes in T cell-receptor diversity occurring with restoration of thymic function. T-cell repertoires were skewed in adults and children at 12 to 18 months after transplantation but recovered to near-normal diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily through peripheral expansion of adoptively transferred donor T cells and results in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells after UCBT is associated with increasing numbers of phenotypicaly naive T cells, improved mitogen and recall antigen responses, and diversification of the T-cell repertoire. The delay in central T-cell recovery in adults relative to children may be due to differences in thymic function resulting from age-related atrophy, graft-versus-host disease, or the pharmacologic effects of prophylaxis and treatment of graft-versus-host disease.

Adolescent↗

Effects of aflatoxin and carotenoids on growth performance and immune response in mule ducklings.

The purpose of this study was to investigate if carotenoids could alleviate the adverse effects caused by aflatoxin with respect to growth performance and immune response. In two experiments, a total of 320 mule ducklings were assigned to 5 treatments, i.e. control, aflatoxin B(1) (AFB(1)) 200 ppb, AFB(1) +beta-carotene (BC) 200 ppm, AFB(1)+BC 400 ppm, and AFB(1)+astaxanthin (AS) 200 ppm. In experiment 1, the addition of beta-carotene or astaxanthin in the diet containing AFB(1) 200 ppb resulted in a significant decrease in average daily gain as compared with the control. AFB(1) 200 ppb alone and the addition of BC or AS on top of AFB(1) resulted in a significantly lower daily feed intake than for the control group. There were no significant differences in relative organ weights among treatment groups. Both treatments of BC 400 ppm and AS 200 ppm had significantly more macrophages harvested per duck than the control and AFB(1) 200 ppb treatments. However, there were no significant differences among treatments in percentages of phagocytotic macrophages and number of Candida albican phagocytized by phagocytotic macrophages. In experiment 2, blood biochemical parameters and antibody titers were evaluated. There were no significant differences among treatments in total bilirubin content and alkaline phosphatase activity in the serum or in antibody titers against fowl cholera. However, AFB(1) treatment had the highest activities of AST and ALT in the serum. The addition of BC 400 ppm on top of AFB(1) significantly reduced ALT activity as compared with the AFB(1) 200 ppb treatment. These results suggest that carotenoids could provide a slightly toxic alleviating effect on growth performance, enhance the chemotaxis ability of macrophages, and reduce ALT activity elevated by AFB(1).

Aflatoxin B1↗

Twenty-one-gauge needles provide more cellular samples than twenty-five-gauge needles in fine-needle aspiration biopsy of the thyroid but may not provide increased diagnostic accuracy.

The technique of fine-needle aspiration (FNA) biopsy of the thyroid is important to evaluate malignancy in thyroid nodules. Eighty-five percent of thyroid FNA procedures lead to sufficient cellular material for diagnosis. With more cells aspirated, the chance of sufficiency for diagnosis increases. Large-bore needles lead to more cellular material being aspirated but bloodier specimens that may interfere with cytologic interpretation. Small-bore needles may result in too few cells for diagnosis. We conducted a randomized prospective study contrasting 21-gauge and 25-gauge needles in the evaluation of 50 consecutively enrolled nodules at our institution. In our investigation, 21-gauge needles more frequently provided superior biopsy specimens (50%) than did 25-gauge needles (18%). In the remaining specimens (32%), the 21-gauge and 25-gauge needles provided similar cellular material. The rate of sufficient samples was the same. We conclude that use of 21-gauge needles results in more cellular specimens but may not result in increased diagnostic accuracy.

Biopsy, Needle↗

Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F.

Triptolide is a diterpenoid triepoxide purified from a Chinese herb Tripterygium Wilfordii Hook F (TWHF). TWHF has been used in traditional Chinese medicine for more than two thousand years. However, its potential value was recognized by the western medicine only after investigators observed the effectiveness of TWHF in the treatment of leprosy and rheumatoid arthritis. Triptolide has been identified as the major component responsible for the immunosuppressive and anti-inflammatory effects of TWHF. Triptolide inhibits both Ca(2+)-dependent and Ca(2+)-independent pathways and affects T cell activation through inhibition of interleukin-2 transcription at a site different from the target of cyclosporin A. Triptolide also has inhibitory effects on a variety of proinflammatory cytokines and mediators and on the expression of adhesion molecules by endothelial cells. Triptolide is effective for the treatment of a variety of autoimmune diseases and in prevention of allograft rejection and graft-versus-host disease in both animals and humans. Moreover, triptolide possesses antitumor and male anti-fertility effect. However, the toxicities of triptolide may be associated with renal, cardiac, hematopoietic and reproductive systems. Currently available data suggest that triptolide is a promising immunosuppressive and anti-inflammatory agent and should be explored further in autoimmune diseases and transplantation.

Animals↗

[Repair and reconstruction of massively damaged wounds].

OBJECTIVE: To report repair and reconstruction of massively damaged wound under unusual condition. METHODS: One hundred and forty-seven patients with deep tissue defects were admitted from January 1993 to December 2000, among them, 96 cases suffered from electrical injury, 18 cases with hot press injury, 18 cases with deep burns as a result of CO poisoning or epileptic seizure, 6 cases caused by chemical producing necrosis and wound infection, 3 cases with radiation injuries, 2 cases with chemical burn, 2 cases with explosive injury, 2 cases with frostbite. One hundred and seventy five wounds in 147 patients were repaired by transfer of local flap, forearm conversal island skin flap, pectoralis major myocutaneous flap, delto-pectoral skin flap, latissimus dorsi skin flap, gastroecnemius myocutaneous flap, anterior and posterior tibial artery island skin flap, and so on. The wound defect ranged from 1 cm x 1 cm to 20 cm x 28 cm, and the flaps were 1.5 cm x 2.0 cm to 22 cm x 30 cm. The necrotic tendon was replaced with acellular allogenic tendon simultaneously in 7 cases. RESULTS: One hundred and sixty-nine flaps were survival with first intention, while necrosis of the tip of flap occurred in 6 cases. The transplantation of acellular allogenic tendon in all cases were survival. The function and configuration in 28 cases were satisfactory after 4 months to 8 years follow-up. CONCLUSION: Various types of flaps are choosen according to the position, defect range and degree of wound, which is an ideal method to restore the function and to improve patients' living condition.

Adolescent↗

Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion.

BACKGROUND: PG490-88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F. METHODS: PG490-88 was administrated into recipient mice in a model (B10.D2-->BALB/c) of lethal graft-versus-host disease (GVHD) to study the effects of PG490-88 on GVHD and on the various steps involved in the pathological course of GVHD. RESULTS: Injection of PG490-88 i.p. at a dose of 0.535 mg/kg/day for the first 3 weeks after transplantation protected all the recipients from developing GVHD up to 100 days after transplantation. PG490-88 inhibited in vivo both CD4+Vbeta3+ and CD8+Vbeta3+ T cell (alloreactive T cells in this model) expansion in the spleen by 64.09 and 34.02%, respectively, at the time when Vbeta3+ cell expansion was in the logarithmic phase (day 3 after transplantation). Intracellular cytokine staining without further in vitro activation demonstrated 47.42% inhibition of IL-2 production among CD4+ spleen cells in PG490-88-treated mice as compared to GVHD control on day 3 after transplantation. In contrast, CD25 (alpha chain of interleukin-2 receptor) expression did not differ. CONCLUSIONS: PG490-88 is highly effective in prevention of murine GVHD. The immunosuppressive effect of PG490-88 is mediated by inhibition of alloreactive T cell expansion through interleukin-2 production.

Animals↗

Graft-versus-host disease prevention by rapamycin: cellular mechanisms.

Understanding the cellular mechanisms that lead to graft-versus-host disease (GVHD) may lead to alternative approaches in the prevention or therapy of this disease process. In this manuscript, we investigated the mechanisms of action of the immunosuppressive drug rapamycin for the prevention of GVHD. GVHD-free long-term survival was achieved in BALB/c (H2d, Mls-2a, Mls-3a) recipients of B10.D2/nSnJ (H-2d, Mls-2a, Mls-3a) bone marrow and spleen cells after a 30-day course of high-dose rapamycin (5 mg/kg per day). Low responses to recipient and third-party cells in a mixed lymphocyte reaction (MLR) were observed as well as decreased mature T-cell numbers in the spleen. This low response was not due to defective interleukin (IL)-2 production, because exogenous IL-2 did not improve the responses in the MLR. However, GVHD-free long-term survival was associated with a large number of infiltrating mononuclear cells in the target organs of GVHD. This observation suggested the possibility that these cells were responsible for suppressing the immune response. Regulatory cells, which could suppress both antirecipient and third-party responses in vitro, were demonstrated to be present in the spleens of these GVHD-free long-term survivors. These results suggest that in addition to impaired cellular immune function, the presence of non-specific regulatory cells (ie, suppression) may contribute to maintenance of GVHD-free long-term survival induced by short-course rapamycin.

Animals↗

Chromium-induced glucose uptake, superoxide anion production, and phagocytosis in cultured pulmonary alveolar macrophages of weanling pigs.

The dose-dependent effects of chromium chloride (CrCl3) and chromium picolinate (CrPic) were evaluated for their glucose uptake, superoxide anion (O2-) production, activity of glucose-6-phosphate dehydrogenase, and phagocytosis of incubated pulmonary alveolar macrophages in medium containing no or 5 x 10(-8)M insulin. Glucose uptake was found to increase in cells treated with 20 microg/L CrCl3. Incubation with 20 microg/L of CrPic enhanced glucose uptake and O2- production in an insulin-dependent manner. However, the inclusion of CrPic to 100 microg/L in the medium absent of insulin also increased O2- production. The activity of glucose-6-phosphate dehydrogenase was not affected by either the addition of Cr or insulin. The phagocytosis of Escherichia coli by macrophages was enhanced significantly (p < 0.05) in medium containing 10-100 microg/L CrCl3 or 20-100 microg/L CrPic in the presence of insulin. These results suggest that the addition of 10-20 microg/L CrCl3 enhances directly the cellular activity of macrophages, whereas the effect of CrPic requires the cooperative action of insulin in enhancing their glucose uptake and phagocytosis.

Animals↗

Managing an animal health emergency in Taipei China: foot and mouth disease.

Taipei China had been free from foot and mouth disease (FMD) over 68 years before the disease occurred in March 1997. The first suspected case was recorded on a pig farm in the Hsinchu Prefecture on 14 March 1997. Based on clinical signs, gross histopathological findings, and results of enzyme-linked immunosorbent assays and reverse-transcriptase polymerase chain reaction tests, diagnosis of FMD was confirmed by the Taiwan Animal Health Research Institute on 19 March 1997 and was reconfirmed by the FMD World Reference Laboratory in Pirbright (United Kingdom), on 25 March 1997. By the end of July 1997, 6,147 pig farms (about a quarter of the pig farms in Taipei China), were affected. The disease was well under control within two months by means of stamping-out and blanket vaccination. The Government purchased 21 million doses of inactivated oil-adjuvant FMD vaccine, which allowed for two injections per pig and one injection of other cloven-hoofed animals. Before the vaccine was used, the stamping-out policy was implemented, ensuring that all pigs in the affected farms were destroyed. After blanket vaccination, a partial stamping-out policy was adopted, i.e. only pigs showing clinical signs were destroyed.

Animals↗

Fresh vs aged benzylpenicillin on non-IgE responses in mice.

AIM: To study whether or not the freshly prepared benzylpenicillin could induce different non-IgE antibody response from aged benzylpenicillin. METHODS: Antibody response was determined by enzyme-linked immunosorbent assay (ELISA). Antigen molecules recognized by antibodies and antigenic cross reactions were tested by hapten inhibition assay. RESULTS: Isotypes of specific non-IgE antibodies induced by freshly prepared benzylpenicillin were mainly IgM, and then IgG and IgA. Some parts of specific antibodies recognized benzylpenicillin molecule and major parts combined with degraded or transforming products. Isotypes of antibodies responsible for cross reaction were mainly IgG between benzylpenicillin and ampicillin and IgM between benzylpenicillin and piperacillin. CONCLUSION: Freshly prepared and aged benzylpenicillin induced different non-IgE antibody response.

Ampicillin↗

Circulating clonal lymphocytes in myeloma constitute a minor subpopulation of B cells.

The mononuclear cells in the blood of myeloma patients have been reported to contain a high proportion of phenotypically abnormal myeloma B lymphocytes. These cells have been proposed to constitute the drug-resistant proliferative myeloma cell compartment. To determine the extent of B lymphocyte involvement, the proportion of clonotypic cells among the CD19-expressing cells from myeloma patients was estimated by quantitative polymerase chain reaction analysis of the third complementarity determining region (CDR3). The results indicate that the B lymphocytes constitute, on average, 6% of blood mononuclear cells, and that only a minor fraction of these are clonally related to the myeloma cells. While the small number of circulating clonal cells is not incompatible with their proposed role as a reservoir of proliferating myeloma progenitors, the majority of the B cells appear not to be clonally related to the myeloma cells.

Antigens, CD19↗

A noninvasive method in the differential diagnosis of vecuronium-induced and magnesium-induced protracted neuromuscular block in a severely preeclamptic patient.

The occurrence of neuromuscular blockade and the resulting potentiation of muscle relaxants during magnesium sulfate (MgSO4) administration is well known. However, a method to differentiate the neuromuscular block induced by magnesium from that induced by curariform nondepolarizing muscle relaxant in the clinical setting has never been reported. We report a case in which the duration of action of 1 mg of vecuronium lasted 4 hours in a patient with severe preeclampsia whose serum magnesium level was in the therapeutic range. We believe this is a remarkable potentiation on record in the literature. We also describe a new, noninvasive method to assess magnesium-induced neuromuscular block when curariform muscle relaxant was given simultaneously.

Adult↗

Suppression of Escherichia coli alkB mutants by Saccharomyces cerevisiae genes.

The alkB gene is one of a group of alkylation-inducible genes in Escherichia coli, and its product protects cells from SN2-type alkylating agents such as methyl methanesulfonate (MMS). However, the precise biochemical function of the AlkB protein remains unknown. Here, we describe the cloning, sequencing, and characterization of three Saccharomyces cerevisiae genes (YFW1, YFW12, and YFW16) that functionally complement E. coli alkB mutant cells. DNA sequence analysis showed that none of the three gene products have any amino acid sequence homology with the AlkB protein. The YFW1 and YFW12 proteins are highly serine and threonine rich, and YFW1 contains a stretch of 28 hydrophobic residues, indicating that it may be a membrane protein. The YFW16 gene turned out to be allelic with the S. cerevisiae STE11 gene. STE11 is a protein kinase known to be involved in pheromone signal transduction in S. cerevisiae; however, the kinase activity is not required for MMS resistance because mutant STE11 proteins lacking kinase activity could still complement E. coli alkB mutants. Despite the fact that YFW1, YFW12, and YFW16/STE11 each confer substantial MMS resistance upon E. coli alkB cells, S. cerevisiae null mutants for each gene were not MMS sensitive. Whether these three genes provide alkylation resistance in E. coli via an alkB-like mechanism remains to be determined, but protection appears to be specific for AlkB-deficient E. coli because none of the genes protect other alkylation-sensitive E. coli strains from killing by MMS.

Alkylation↗

The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity.

Escherichia coli can ameliorate the toxic effects of alkylating agents either by preventing DNA alkylation or by repairing DNA alkylation damage. The alkylation-sensitive phenotype of E. coli alkB mutants marks the alkB pathway as an extremely effective defense mechanism against the cytotoxic effects of the SN2, but not the SN1, alkylating agents. Although it is clear that AlkB helps cells to better handle alkylated DNA, no DNA alkylation repair function could be assigned to the purified AlkB protein, suggesting that AlkB either acts as part of a complex or acts to regulate the expression of other genes whose products are directly responsible for alkylation resistance. However, here we present evidence that the provision of alkylation resistance is an intrinsic function of the AlkB protein per se. We expressed the E. coli AlkB protein in two human cell lines and found that it confers the same characteristic alkylation-resistant phenotype in this foreign environment as it does in E. coli. AlkB expression rendered human cells extremely resistant to cell killing by the SN2 but not the SN1 alkylating agents but did not affect the ability of dimethyl sulfate (an SN2 agent) to alkylate the genome. We infer that SN2 agents produce a class of DNA damage that is not efficiently produced by SN1 agents and that AlkB somehow prevents this damage from killing the cell.

AlkB Homolog 1, Histone H2a Dioxygenase↗