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Biomedical subjects

M J Wu

Publications and source records attributed to M J Wu.

At least 19 recordsLinked to original sources
PubMed2006

Acute pancreatitis following antilymphocyte globulin therapy in a renal transplant recipient.

Acute pancreatitis is a rare complication following OKT3 therapy, which to our knowledge has never been reported in patients treated with antilymphocyte globulin (ALG). We herein report a case of a kidney transplantation patient who developed acute pancreatitis 2 days after treatment with ALG for grade IIb acute rejection. The symptoms subsided after discontinuing this drug. Resumption of ALG therapy triggered another episode of acute pancreatitis. Therefore, the clinical course strongly suggests that ALG was the etiological factor of acute pancreatitis in this particular patient.

Acute Disease↗
PubMed2004

Sirolimus in chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is the most common cause of late renal transplant loss. Calcineurin inhibitor (CNI) nephrotoxicity is known to contribute to CAN. A sirolimus-based regimen way allow for early CNI reduction or elimination. The aim of the present study was to determine the efficacy and safety of a sirolimus-based regimen for CAN. From December 2001 to August 2003, kidney transplant (KTx) recipients with CAN were enrolled for treatment with sirolimus. Among 32 studied patients, 24 (75%) underwent graft biopsy before the initiation of sirolimus. Baseline maintenance immunosuppression consisted of cyclosporine/tacrolimus and prednisone with or without mycophenolate mofetil. The follow-up duration on sirolimus therapy was 8.5 +/- 5.9 months (range: 1 to 22 months). The average dosage of sirolimus was 1.8 +/- 0.5 mg/d at the end of follow-up. The mean trough level of sirolimus was 5.1 +/- 2.1 ng/mL. Sirolimus was effective in 16 (50%) patients while 3 (9.4%) patients improved (serum creatinine [Cr] decrease > 10%) and 13 (40.6%) maintained stable (change of serum Cr within 10%). Sirolimus was effective in 5 (35.7%) patients whose serum Cr was over 3.0 mg/dL but failed to rescue all four patients whose serum Cr was over 4.0 mg/dL. Eleven (68.8%) of 16 responders showed a reduction (29.8% +/- 13.8%) in CNI dosage. The most common adverse events were hyperlipidemia (37.5%), anemia (25%), and diarrhea (21.8%). Twelve patients discontinued sirolimus due to graft failure (4), severe infection (3), stroke related mortality (1), anemia (2), diarrhea (1), and edema (1). In conclusion, sirolimus is effective in 50% of KTx recipients with CAN, especially when the serum Cr is less than 3.0 mg/dL. However, the increased incidence of infection, diarrhea, and hyperlipidemia are of major concern.

Adult↗
PubMed2004

Tuberculosis in patients with end-stage renal disease.

OBJECTIVE: To elucidate the clinical manifestations and risk factors of the mortality rate in uraemic patients with tuberculosis (TB) infection. DESIGN: We retrospectively analysed 62 patients with uraemia and active tuberculosis who were admitted to our hospital from 1990 through 2000. The patients were followed up for 2 years after discharge or until death. RESULTS: There were 43 men and 19 women, with a mean age of 63 +/- 13 years. Extra-pulmonary TB was noted in 51.6%. The peritoneum and pleura were the two most common organs involved. Fever of unknown origin was the most common manifestation (77.4%). The corrected serum Ca2+ level of the patients was >10.5 mg/dl in 46.8%. C-reactive protein >6 mg/dl and leukocytosis (white blood cell count >10,000/mm3) at presentation were noted in more than half of the patients. A reversed serum albumin/globulin ratio and leukocytosis were found to be associated with mortality rate. CONCLUSION: More than half of the TB infections in patients with end-stage renal disease presented with extra-pulmonary involvement. Fever of unknown origin, reversed serum albumin/globulin ratio, and unexplained hypercalcaemia in maintenance dialysis patients suggested the possibility of tuberculosis.

Age Distribution↗
PubMed2003

Cell migration: a novel aspect of pancreatic stellate cell biology.

BACKGROUND: Pancreatic stellate cells (PSCs), implicated as key mediators of pancreatic fibrogenesis, are found in increased numbers in areas of pancreatic injury. This increase in PSC number may be due to increased local proliferation and/or migration of these cells from adjacent areas. The ability of PSCs to proliferate has been well established but their potential for migration has not been examined. AIMS: Therefore, the aims of this study were to determine whether cultured rat PSCs have the capacity to migrate and, if so, to characterise this migratory capacity with respect to the influence of basement membrane components and the effect of platelet derived growth factor (PDGF, a known stimulant for migration of other cell types). METHODS: Migration of freshly isolated (quiescent) and culture activated (passaged) rat PSCs was assessed across uncoated or Matrigel (a basement membrane-like substance) coated porous membranes (pore size 8 micro m) in the presence or absence of PDGF (10 and 20 ng/ml) in the culture medium. A checkerboard assay was performed to assess whether the effect of PDGF on PSC migration was chemotactic or chemokinetic. RESULTS: Cell migration was observed with both freshly isolated and passaged PSCs. However, compared with passaged (culture activated) cells, migration of freshly isolated cells was delayed, occurring only at or after 48 hours of incubation when the cells displayed an activated phenotype. PSC migration through Matrigel coated membranes was delayed but not prevented by basement membrane components. PSC migration was increased by PDGF and this effect was predominantly chemotactic (that is, in the direction of a positive concentration gradient). CONCLUSIONS: (i) PSCs have the capacity to migrate. (ii) Activation of PSCs appears to be a prerequisite for migration. (iii) PDGF stimulates PSC migration and this effect is predominantly chemotactic. IMPLICATION: Chemotactic factors released during pancreatic injury may stimulate the migration of PSCs through surrounding basement membrane towards affected areas of the gland.

Animals↗
PubMed2002

Non-point source pesticide removal by a mountainous wetland.

Non-point source (NPS) pollution is believed to be one of the major causes of impairment of water bodies. Among NPS pollution, agricultural NPS pollution is considered to be the largest single category resulting in water quality deterioration. Pesticides are some the most ubiquitous of these agricultural NPS pollutants. In this study, a mountainous wetland was selected to investigate the effects of the natural wetland system on the NPS pesticide (atrazine) removal to maintain the surface water quality. The selected wetland receives water from two unnamed creeks, which drain primarily upgradient agricultural lands. Wetland investigation and monitoring were conducted from November 1999 to March 2001. Major storm events and baseline water quality samples were analyzed. Field results indicate that the wetland was able to remove NPS atrazine flushed from the upgradient agricultural lands after the occurrence of storm events. Laboratory aerobic and anaerobic bioreactor experiments were conducted to evaluate the biodegradation of atrazine under the intrinsic conditions of the wetland system. Microbial enumeration was conducted for a quick screen of bacterial activity in the studied wetland. Results from the study suggest that the methanogenesis process was possibly the dominant biodegradation pattern, and atrazine can be degraded under reductive dechlorinating conditions when sufficient intrinsic organic matter was provided. Results from this study can provide us with further knowledge on pesticide removal mechanisms in natural wetlands and evaluate the role of wetlands in controlling pesticide pollutants from stormwater runoff.

Agriculture↗
PubMed2001

Synthesis and antitumor activity of novel C-7 paclitaxel ethers: discovery of BMS-184476.

The preparation of C-7 paclitaxel ethers is described. Various substituted ethers were prepared via activation of the corresponding methylthiomethyl ether followed by alcohol addition. Variation of the C-7 ether group as well the 3' side chain position led to the discovery of a novel taxane, BMS-184476 (4), with preclinical antitumor activity superior to paclitaxel.

Antineoplastic Agents↗
PubMed2001

A regulatory region rearranged BK virus is associated with tubulointerstitial nephritis in a rejected renal allograft.

A renal allograft transplant patient with high serum creatinine presented clinical symptoms of rejection. Sections of renal biopsy tissue showed mononuclear leukocyte infiltration in the tubulointerstitium and nuclear enlargement with inclusions in the tubular epithelium. The morphological characteristics resembled polyomavirus-induced interstitial nephritis. Electron microscopy of the nuclear inclusions showed paracrystalline arrays of naked viral particles with a diameter of 45 nm. Molecular studies revealed that a new variant of BK virus (BKV) with rearrangement at the regulatory region was involved in the nephritis. The BKV regulatory region contained a tandem repeat from the P-block to the Q-block causing duplication of several important transcriptional elements or transcriptional factor binding motifs. This is the first report to show a naturally occurring BKV variant with regulatory region rearrangement associated with tubulointerstitial nephritis.

Adult↗
PubMed2001

Evaluation of TCDD biodegradability under different redox conditions.

Polychlorinated dibenzo-p-dioxins have been generated as unwanted by-products in many industrial processes. Although their widespread distribution in different environmental compartments has been recognized, little is known about their fate in the ultimate environment sinks. The highly stable dioxin isomer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been called the most toxic compound known to man. In this laboratory microcosm study, TCDD bioavailability was evaluated under five reduction/oxidation (redox) conditions including aerobic biodegradation, aerobic cometabolism, methanogenesis, iron reduction, and reductive dechlorination. Activated sludge and aquifer sediments from a TCDD and a pentachlorophenol (PCP) contaminated site were used as the inocula. Acetate, sludge cake, and cane molasses were used as the primary substrates (carbon sources) in cometabolism and reductive dechlorination microcosms. After a 90-day incubation period, microcosms constructed under reductive dechlorination conditions were the only treatment showing promising remediation results. The highest TCDD degradation rate [up to 86% of TCDD removal (with an initial concentration of 96 microg/kg of soil)] was observed in the microcosms with anaerobic activated sludge as the microbial inocula and sludge cakes as the primary substrates. Except for reductive dechlorination microcosms, no significant TCDD removal was observed in the microcosms prepared under other conditions. Thus, application of an effective primary substrate to enhance the reductive dechlorination process is a feasible method for TCDD bioremediation. Bioremediation expense can be significantly reduced by the supplement of some less expensive alternative substrates (e.g., sludge cakes, cane molasses). Results would be useful in designing a scale-up in situ or on-site bioremediation system such as bioslurry reactor for field application.

Bacteria, Aerobic↗
PubMed2001

A series of enediynes as novel inhibitors of topoisomerase I.

A series of acyclic enediynes, 2-((6-substituted)-3-hexen-1,5-diynyl)benzonitriles (8--11), display potent inhibition against topoisomerase I without the formation of active biradical intermediates and show inhibitory activity against topoisomerase I at 10 microM, which is five times that of camptothecin from the results of agarose gel electrophoresis.

Camptothecin↗
PubMed2001

Lamivudine is effective for the treatment of reactivation of hepatitis B virus and fulminant hepatic failure in renal transplant recipients.

Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. The aim of this study is to elucidate the effectiveness of lamivudine for the treatment of HBV reactivation with or without fulminant hepatic failure in renal transplant recipients. Forty-two renal transplant recipients (30 men, 12 women) were enrolled onto this study. Eight patients presented with HBV reactivation without fulminant hepatic failure and were administered lamivudine (group I), 5 patients presented with HBV and hepatic failure and were administered lamivudine (group II), 5 patients presented with HBV and hepatic failure but were not administered lamivudine (group III), and 24 patients were asymptomatic HBV carriers who were not administered lamivudine (group IV). Lamivudine was administered at a dose of 100 or 150 mg once daily. A greater prevalence of recent use of a combination of antilymphocyte immunoglobulin (ALG) and methylprednisolone (MP) occurred in patients with hepatic failure (groups II and III) than those without hepatic failure (30% versus 6.3%; P = 0.043). However, there was no significant difference in the incidence of MP use alone (20% versus 25%; P = 0.746). Mortality rates for groups I, II, and III were significantly different (12.5%, 40%, 100%; P = 0.008). One patient in group I died of sepsis without evidence of HBV DNA, even in the terminal event. In group II, 3 of 5 patients (60%) were rescued by lamivudine therapy. In group III, without lamivudine treatment, there was a 100% mortality rate despite intensive plasmapheresis. HBV DNA was not detectable after lamivudine treatment in 7 of 8 patients in group I and 3 of 5 patients in group II. Creatinine levels did not change significantly during lamivudine treatment. Hepatitis B surface antigen and hepatitis B e antigen seroconversion rates after lamivudine treatment were 7.7% and 37.5%, respectively. We conclude that ALG is a potent trigger of HBV-related fulminant hepatic failure in renal transplant recipients, whereas lamivudine is an effective and lifesaving treatment. Prompt use of lamivudine is recommended in renal transplant recipients with evidence of HBV reactivation to prevent catastrophic fulminant hepatic failure.

Adolescent↗
PubMed2001

Control of non-point source pollution by a natural wetland.

Wetland creation and restoration is a reliable and efficient technology for the remediation of contaminated water. Knowledge from the natural wetland systems would be necessary to enhance the operational efficiency of constructed wetlands. In this study, a mountainous wetland located in McDowell County, North Carolina, USA was selected to demonstrate the effects of the natural filtration and restoration system on the maintenance of surface water quality. The hydraulic retention time (HRT) for the wetland was 10.5 days based on the results from a dye release study. Water quality monitoring of the wetland was conducted from May to August 1997. One major storm event and baseline water quality samples were collected and analyzed. Analytical results indicate that this wetland removed a significant amount of non-point source (NPS) pollutants [more than 80% N removal, 91% of total suspended solid removal, 59% of total phosphorus removal, and 66% of chemical oxygen demand (COD) removal] caused by the studied storm event. Sediment accretion monitoring results indicate that the accretion rate in the wetland was only 4 mm/year. Therefore, the wetland would require 100 years to fill at the measured sediment accretion rate. The high organic content of sediments (16%) indicates that the wetland is building the characteristic organic layer on the bottom of the wetland. Results from this study would be very useful in the maintenance of natural wetlands and design of constructed wetlands for water treatment.

Conservation of Natural Resources↗
PubMed2001

Evaluation of atrazine removal processes in a wetland.

Agricultural non-point source (NPS) pollution is considered to be the largest single category resulting in water quality deterioration. Pesticide is one of the main detrimental agricultural NPS constituents causing the impairment of water bodies. In this study, a mountainous wetland located in McDowell County, North Carolina, was selected to demonstrate the effects of the natural wetland system on the removal of NPS pesticide (atrazine) pollution to maintain the surface water quality. The selected wetland receives water from two unnamed creeks, which drain primarily agricultural lands. The hydraulic retention time (HRT) for the wetland was approximately 10.5 days based on the results from a dye release study. Water quality monitoring of the wetland was conducted from March to October 1998. One major storm and baseline water quality samples were analyzed. Analytical results indicate that the wetland completely removed NPS atrazine flushed from the upgradient agricultural lands. Laboratory microcosm experiments were conducted to evaluate the feasibility of using the wetland sediments as the microbial sources to enhance the atrazine biodegradation. Microcosm results suggest that atrazine can be degraded under anaerobic or reductive dechlorinating conditions when sucrose was provided as the primary substrate. Atrazine can also serve as the nitrogen source for the growth of microorganisms under anaerobic conditions. Results from this study can provide us with further knowledge on evaluating the role of wetlands in controlling pesticide pollutants from stormwater runoff.

Agriculture↗
PubMed2000

Enhanced TCDD degradation by Fenton's reagent preoxidation.

The dioxin isomer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been called the most toxic compound known to man. Because of its poor bioavailability and low biodegradibility, bioremediation technology cannot effectively degrade TCDD when used alone. In this study, chemical pretreatment (partial oxidation) in combination with biodegradation technique was developed to efficiently remediate TCDD-contaminated soils. An oxidizing reagent [Fenton's Reagent (FR)] was applied in a slurry reactor to transform TCDD with a concentration of 96 microg per kg of soil to compounds more amenable to biodegradation. Up to 99% TCDD was transformed after the chemical pretreatment process. The slurry reactor was then converted to a bioreactor for the following biodegradation experiment. The detected TCDD oxidation byproducts including chlorophenols (CPs) and chlorobenzenes (CBs) were transformed in this bioreactor under aerobic conditions. Two other biodegradation experiments were performed in parallel to investigate the biodegradabiliy of TCDD under aerobic and anaerobic conditions without chemical pretreatment. Approximately 53% TCDD was transformed under anaerobic conditions possibly due to the reductive dechlorination process using organic materials contained in the activated sludge as the primary substrates. No TCDD degradation was observed under aerobic conditions. Results show that FR can oxidize TCDD to less-chlorinated and less-toxic byproducts, promoting their bioavailability to microbial communities. The bench-scale results indicate that the two-stage (partial oxidation followed by biodegradation) system has the potential to be developed to remediate TCDD-contaminated soils on-site.

Biodegradation, Environmental↗
PubMed2000

GTP binding and signaling by Gh/transglutaminase II involves distinct residues in a unique GTP-binding pocket.

G(h) is a dual function protein. It has receptor signaling activity that requires GTP binding and Ca(2+)-activated transglutaminase (TGase) activity that is inhibited by GTP binding. G(h) shows no homology with other GTP-binding proteins, and its GTP-binding site has not been defined. Based on sequence analysis of [alpha-(32)P]GTP-photolabeled and proteolytically released internal peptide fragments, we report localization of GTP binding to a 15-residue segment ((159)YVLTQQGFIYQGSVK(173)) of the G(h) core domain. This was confirmed by site-directed mutagenesis; a G(h)/fXIIIA chimera (in which residues 162-179 of G(h) were substituted with the equivalent but nonhomologous region of the non-GTP-binding TGase factor XIIIA) and a G(h) point mutant, S171E, retained TGase activity but failed to bind and hydrolyze GTP and did not support alpha(1B)-adrenergic receptor signaling. Slight impairment of GTP binding (1.5-fold) and hydrolysis (10-fold) in the absence of altered TGase activity did not affect signaling by the mutant K173N. However, greater impairment of GTP binding (6-fold) and hydrolysis (50-fold) abolished signaling by the mutant K173L. Mutant S171C exhibited enhanced GTP binding and signaling. Thus, residues Ser(171) and Lys(173) are critical for both GTP binding and signaling but not TGase activity. Mutagenesis of residues N-terminal to Gly(170) impaired both GTP binding and TGase activity. From computer modeling of G(h), it is evident that the GTP-binding region identified here is distinct from, but interacts with, the TGase active site. Together with structural considerations of G(h) versus other GTP-binding proteins, these findings indicate that G(h) has a unique GTP-binding pocket and provide for the first time a mechanism for GTP-mediated regulation of the TGase activity of G(h).

Amino Acid Sequence↗
PubMed2000

Exposure to solvents in a synthetic leather manufacturing plant.

The objective of this study was to evaluate the exposure of synthetic leather workers to dimethylformamide (DMF), epichlorohydrin (ECH) and toluene, in a manufacturing plant. The correlation between biological and environmental monitoring for DMF was also investigated. Environmental monitoring of the three solvents included personal and area sampling based on time of day (morning and afternoon). Urine samples were taken at the end of the shift and urinary N-methylformamide (NMF) was then used to biologically monitor DMF levels. Results for solvent concentrations based on air sampling were considerably higher in area than in personal sampling. Of 41 area samples, 15 (36.6%) and five (12.2%) exceeded permissible exposure levels for DMF and ECH, respectively, compared with 22 (28.6%) and three (3.9%) based on 77 personal samples. Overall, urinary NMF concentrations were lower than the Biological Exposure Index (BEI) suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). A significant correlation (r = 0.32; P < 0.05) was found between environmental and biological monitoring. Even though urinary NMF concentration was within permissible levels for Taiwan, the authors recommend that immediate measures be taken to decrease DMF and ECH concentrations in synthetic leather manufacturing plants.

Adult↗