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H W Wu

Publications and source records attributed to H W Wu.

At least 19 recordsLinked to original sources

Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection.

We conducted a prospective cohort study in Leyte, the Philippines, among 611 Schistosoma japonicum-infected participants 7-30 years old, all of whom were treated with praziquantel at baseline. To detect hepatic fibrosis, abdominal ultrasound was performed at baseline and 12 months after treatment. Stool for assessment of S. japonicum infection was collected at baseline and at 3, 6, 9, and 12 months after treatment. Cytokines (interleukin [IL]-4, IL-5, IL-10, IL-13, tumor necrosis factor- alpha , and interferon- gamma ) produced by peripheral-blood mononuclear cells in response to soluble worm antigen preparation (SWAP), soluble egg antigen (SEA), and control medium were measured once 4 weeks after treatment. IL-4 to SWAP and IL-10 to both SWAP and SEA were associated with the presence of baseline fibrosis after adjustment for potential confounding variables (P<.03, for all). In participants with fibrosis at baseline, IL-4 to SWAP and IL-5 and IL-13 to both SWAP and SEA were associated with persistent fibrosis at 12 months after treatment (P<.05, for all). Males showed consistently stronger T helper 2 (Th2) cytokine responses to both SWAP and SEA than did females (P<.02, for all). These results suggest an independent role for Th2-biased cytokine responses to S. japonicum antigens in persistent hepatic fibrosis and indicate that Th2 cytokines may contribute to the male-biased prevalence of fibrosis.

Adolescent↗

Sustained activation of Src-family tyrosine kinases by ischemia: a potential mechanism mediating extracellular signal-regulated kinase cascades in hippocampal dentate gyrus.

In the present report, we investigated the association between the sustained activation of Src family tyrosine kinases (primarily Src kinase) with the biphasic phosphorylation of extracellular signal-regulated kinase (ERK) induced by ischemia in the rat hippocampal CA3/dentate gyrus subfield. Post-ischemia reperfusion resulted in the phosphorylation of ERK in a Ras-dependent manner; down-regulation of NMDA receptors or Src family protein kinases by ketamine or 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2) potently antagonized the activation of ERK, indicating that NMDA receptors and Src family tyrosine kinases are essential for the up-regulation of ERK activity following ischemic stimuli. Additionally, an ischemia-induced association between RKIP and Raf-1 resulted in the inhibition of the ERK signaling cascade through an inhibition of Src-mediated Raf-1 phosphorylation at Tyr340/341 residues. This ischemia-induced inhibition of ERK was not associated with other downstream pathways involving Raf-1 phosphorylation at Ser 259 elicited by protein kinase B (Akt). Dissociation of Raf-1 from RKIP by 24 h reperfusion or (4S)-3-[(E)-but-2-enoyl]-4-benzyl-2-oxazolidinone (locostatin) influenced the second phase of ERK activation elicited by the Src-Raf cassette. We propose that, following ischemia, the Src family tyrosine kinases are critical for modulation of the Ras/Raf/MEK/ERK cascade, in which RKIP is involved in biphasic phosphorylation of ERK via a blockade of Src-Raf cascades.

Animals↗

IFN-gamma is associated with risk of Schistosoma japonicum infection in China.

Before the start of the schistosomiasis transmission season, 129 villagers resident on a Schistosoma japonicum-endemic island in Poyang Lake, Jiangxi Province, 64 of whom were stool-positive for S. japonicum eggs by the Kato method and 65 negative, were treated with praziquantel. Forty-five days later the 93 subjects who presented for follow-up were all stool-negative. Blood samples were collected from all 93 individuals. S. japonicum soluble worm antigen (SWAP) and soluble egg antigen (SEA) stimulated IL-4, IL-5 and IFN-gamma production in whole-blood cultures were measured by ELISA. All the subjects were interviewed nine times during the subsequent transmission season to estimate the intensity of their contact with potentially infective snail habitats, and the subjects were all re-screened for S. japonicum by the Kato method at the end of the transmission season. Fourteen subjects were found to be infected at that time. There was some indication that the risk of infection might be associated with gender (with females being at higher risk) and with the intensity of water contact, and there was evidence that levels of SEA-induced IFN-gamma production were associated with reduced risk of infection.

Adolescent↗

Down-regulation of specific antigen-driven cytokine production in a population with endemic Schistosoma japonicum infection.

Schistosome antigen-driven cytokine responses and antischistosome antibody levels of residents of a Schistosoma japonicum endemic island in Poyang Lake, Jiangxi Province were studied before and 45 days after treatment with praziquantel. IL-4, IL-5, IL-10 and INF-gamma were all detected in the supernatants of whole-blood cultures after stimulation with schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP). The percentages of subjects producing detectable amounts of each cytokine assayed were higher in the group who were negative by stool examination at the start of the study than in those who were initially stool positive. After praziquantel treatment the percentages of subjects producing both type I and type II cytokines increased. This suggests that the production of both types of cytokine was down-regulated in the presence of live, egg-laying S. japonicum adult worms but that this was reversible by treatment. In contrast, the antibody studies showed higher levels of SWAP and SEA-specific antibodies (IgE, total IgG, IgG4, IgM) in subjects who were originally stool-positive than in those who were stool-negative. After treatment specific IgE responses were elevated, but total IgG and IgG4 anti-SEA and IgM anti-SWAP antibody levels all fell significantly.

Adolescent↗

[Histomorphometric analysis in ovariectomized rat with osteoporosis].

OBJECTIVE: To establish the pattern of bone loss of Sprague-Dawley rats after ovariectomy, to investigate and assess the pattern of bone remodeling in ovariectomized rats and the therapeutic action of nilestriol and levenorgestrel. METHODS: Histomorphometric analysis for bone tissues was performed with the instrument of computerized image analysis. RESULTS: The trabecular bone volume, mean trabecular thickness, and trabecular bone perimeter were all significantly decreased (P < 0.01) in ovariectomized rats in the 14th week postsurgery compared to the sham operated group. But the osteoblastic index, osteoclastic index, resorptive surface of trabecular, and trabecular surface covered by osteoblast were significantly increased (P < 0.01). There was no significant difference between the treatment group and the sham operated group. CONCLUSIONS: The pattern of bone loss of rats after ovariectomy has been established successfully. The study provides evidence that the cause of bone loss in the ovariectomized rats is attributable to the increase of bone turnover and negative imbalance in bone remodeling process. The treatment of nilestriol and levenorgestrel may decrease the bone turnover and correct the imbalance to cure the osteoporosis.

Animals↗

Human NKT cells mediate antitumor cytotoxicity directly by recognizing target cell CD1d with bound ligand or indirectly by producing IL-2 to activate NK cells.

alpha-Galactosylceramide (alphaGalCer) stimulates NKT cells and has antitumor activity in mice. Murine NKT cells may directly kill tumor cells and induce NK cell cytotoxicity, but the mechanisms are not well defined. Newly developed human CD1d/alphaGalCer tetrameric complexes were used to obtain highly purified human alphaGalCer-reactive NKT cell lines (>99%), and the mechanisms of NKT cell cytotoxicity and activation of NK cells were investigated. Human NKT cells were cytotoxic against CD1d(-) neuroblastoma cells only when they were rendered CD1d(+) by transfection and pulsed with alphaGalCer. Four other CD1d(-) tumor cell lines of diverse origin were resistant to NKT cells, whereas Jurkat and U937 leukemia cell lines, which are constitutively CD1d(+), were killed. Killing of the latter was greatly augmented in the presence of alphaGalCer. Upon human CD1d/alphaGalCer recognition, NKT cells induced potent cytotoxicity of NK cells against CD1d(-) neuroblastoma cell lines that were not killed directly by NKT cells. NK cell activation depended upon NKT cell production of IL-2, and was enhanced by secretion of IFN-gamma. These data demonstrate that cytotoxicity of human NKT cells can be CD1d and ligand dependent, and that TCR-stimulated NKT cells produce IL-2 that is required to induce NK cell cytotoxicity. Thus, NKT cells can mediate potent antitumor activity both directly by targeting CD1d and indirectly by activating NK cells.

Adjuvants, Immunologic↗

[Comprehensive assessment of the ovariectomized rat model of postmenopausal osteoporosis].

Dual-energy X-ray absorptiometry(DEXA), scanning electron microscopy, and bone biomechanical test were used to assess comprehensively bone quantity and quality of ovariectomized rats. In OVX rats, not only bone mineral density (BMD) of lumbar vertebrae in vivo and vitro, but also BMD of femora (except for R3 region) and proximal metaphysis(R1 region) in vitro decreased obviously (P < 0.01), whose bone loss rates of L5 and L6 were the highest and achieved 13%; the trabeculae of OVX rats were few, fine, and discontinued and there were lacunae on the surface; in OVX rats, both compressive strength of vertebral bodies and the mechanical properties of femora decreased; the falling degree of the former was greater; the maximal compressive power of lumbar vertebrae decreased with 33.32%. We conclude that after 4-month post-ovariectomy, the bone quantity and quality of six-month-old rats decreased, especially in the area of abundant cancellous bone such as vertebral bodies, distal femora; the assessment of the efficiency of new drugs to prevent and treat postmenopausal osteoporosis using rat models should include these drugs' effects to the bone mass, the bone structure, and the bone strength.

Absorptiometry, Photon↗

Surface ozone trends in Hong Kong in 1985-1995.

Ozone trends in Hong Kong were assessed from the ozone data recorded at three urban stations and one station in the new development area. Three parameters were selected as the robust trend indicators in the study: monthly mean, monthly averaged daily 1-h maximum, and number of annual hours > 120 microg m(-3). As the ozone data displayed obvious seasonal variation, using deseasonalized monthly average parameters to estimate the ozone trends could smooth out the influence of seasonal fluctuations. The detection of an increase of more than 10% per year in ozone concentration at one station was particularly alarming. Effects of meteorological factors, control programmes of ozone precursors, and long-range transport on the ambient ozone level were examined in the study.

Air Pollutants↗

[Analysis of the mitochondria-related protein of Schistosoma japonicum and its antigen epitopes].

OBJECTIVE: To sequence the cloned gene Sj338 and to identify the encoded protein and its antigen epitopes. METHODS: The Sj338 gene fragment obtained from adult S. japonicum cDNA library amplified by PCR method was subcloned into pGEM-T vector for sequencing. The sequence of nucleotides and the characteristics of the encoded protein were analyzed by DNASIS Program and Goldkey DNA and Protein Analytical Program, and then the homology of the amino acid sequence was searched on the BLAST net. RESULTS: The cloned rSj338 gene was demonstrated to be 487 bp containing one 459 bp ORF, encoding a protein consisted of 153 amino acids with a molecular weight of 17.6 kDa. The amino acid sequence of the recombinant protein rSj338 shared 46% identity with that of the corresponding part of human mitochondrial import receptor and 44% identity with that of the Rattus sp. mitochondrial precursor receptor. The possible antigen epitopes were predicted within the peptide fragments of 26-32 aa, 37-46 aa and 147-151 aa. CONCLUSION: The protein encoded by rSj338 gene fragment might be the mitochondria-related protein of Schistosoma japonicum.

Amino Acid Sequence↗

[Bone mineral density characteristics at the femoral neck and Ward's triangle for Chinese women].

The incidence of hip fracture is not as high in Chinese women compared to women from Western countries, though they usually have low bone mineral density(BMD) and get osteopenia easily. In this study, reference data(white women) supplied by the manufacturer of Hologic was compared with data obtained from healthy women in Changsha, Hunan, P.R.C. One thousand four hundred and eighty-eight Chinese women aged 15 to 95 years were randomly recruited. Measurements of BMD were taken at the hip by the dual energy x-ray absorptiometry(QDR 4,500A, Hologic Inc., USA). The BMD was somewhat lower than reference curves at all ages and all sites. But at the femoral neck and Ward's triangle, Chinese women reached their peak BMD 5 to 10 years later than the reference group, and had a lower BMD rate of decrease for about 35 years after peak BMD was reached. Whether the differences(i.e., longer time to peak BMD and a lower BMD decrease rate at the neck and Ward's triangle after the peak BMD reached) will result in a protection from hip fractures for Chinese women needs to be studied in the future.

Absorptiometry, Photon↗

Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis.

We have identified human and mouse peroxiredoxin V (Prx-V) by virtue of the sequence homologies to yeast peroxisomal antioxidant enzyme PMP20. Prx-V represents the fifth of the six currently known subfamilies of mammalian peroxiredoxins. It is a novel organellar enzyme that has orthologs in bacteria. Biochemically, Prx-V is a thioredoxin peroxidase. One important aspect of p53 function in mammalian cells involves induction of apoptosis likely mediated by redox. We show that overexpression of Prx-V prevented the p53-dependent generation of reactive oxygen species. Likewise, Prx-V inhibited p53-induced apoptosis. Thus, Prx-V is critically involved in intracellular redox signaling.

Amino Acid Sequence↗

Integration of computer-assembled digital images and text data as evidence for the oncological record.

Digitally created visual images of pertinent patient data have been integrated with text information to formulate a visual evaluation and summary sheet (VESS) using computer processing. The VESS incorporates images of a patient's physical appearance, radiological images, pharmacokinetic graphs, and text information into a 1-page document of the patient's condition. Thus, computer processing of digital images and other information helps to refine patient data presentation, analysis, interpretation, and communication. This form of data management is especially valuable in oncological research, where clinical trials demand rapid, ongoing assessment of results and analysis of large amounts of data. The VESS is an effective mechanism for monitoring both the progress of individual patients and the endpoints of the overall clinical trial.

Diagnostic Imaging↗

Phase II study of tamoxifen, ifosfamide, epirubicin and cisplatin combination chemotherapy in patients with non-small cell lung cancer failing previous chemotherapy.

We conducted a phase II study of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy in patients with non-small cell lung cancer (NSCLC) who had failed previous chemotherapy, in order to assess the response and toxicity of TIEP. Between November 1997 and May 1999, 25 patients were treated. Twelve of the 25 patients (48%) had been previously treated with cisplatin-based combination chemotherapy. TIEP doses were tamoxifen 60 mg oral twice daily on days 1-3; ifosfamide 2.4 g/m(2) intravenous infusion (IV) 60 min with mesna on day 2; epirubicin 40 mg/m(2) IV bolus on day 2; and cisplatin 50 mg/m(2) IV 60 min on day 2 every 4 weeks for up to six cycles. Seventy one cycles were given to 25 patients, with a median of three cycles (range one to six cycles). All patients were evaluable for toxicity profile and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 15 patients (60%) during treatment, as well as in 31% of the total courses. Febrile neutropenia occurred in two patients. No toxic death occurred in this study. Grade 3 thrombocytopenia occurred in five patients with five cycles. Toxicities other than myelosuppression were few and mild in severity. After two cycles of treatment, five of 25 patients (20%) had a partial response (95% confidence interval 4.3-35.7%). Among 12 patients previously treated with cisplatin-based chemotherapy, three patients (25%) achieved a partial response. The median time to disease progression was 4.9 months and median survival was 7.7 months. The response rate and median survival were better than in our previous study of salvage chemotherapy with ifosfamide, 5-FU, and leucovorin; and with ifosfamide, epirubicin, 5-FU, and leucovorin. In conclusion, TIEP appears to be an active combination regimen with an acceptable toxicity profile in Chinese patients with NSCLC who have failed previous chemotherapy.

Adenocarcinoma↗

Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer.

The aim of the present study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine, ifosfamide and cisplatin (GIP), administered every 3 weeks, in patients with inoperable non-small cell lung cancer (NSCLC). From October 1998 to July 1999, 18 previously untreated stages IIIb (4) and IV (14) patients were enrolled into the study. Gemcitabine and ifosfamide (with mesna as uroprotection) was administered on days 1 and 6, at a dose of 1000 and 1500 mg/m2, respectively; and cisplatin was given on day 1 at a dose of 60 mg/m2, every 3 weeks. All 18 patients were evaluable for response and toxicity profiles. One patient achieved a complete response, and II patients achieved a partial response, with an overall response rate of 66.7% (95%, CI, 45-89%). The main toxicity was hematological, a NCI grade 3-4 neutropenia in 16 patients (88.9%) during the treatment course. Febrile neutropenia occurred in three patients (16.6%). Grade 3 anemia occurred in eight patients (44.41%) and grade 3-4 thrombocytopenia occurred in 11 patients (61.1%). Non-hematological toxicity was mild and tolerable. No toxic death occurred. The median survival was 12.7 months and 1 year survival was 58.4%. The GIP combination chemotherapy produced a high response rate in advanced NSCLC; however, there was a relatively high percentage of hematological toxicity that still could be tolerated. A randomized trial comparing GIP to a two-drug combination of gemcitabine and cisplatin is planned.

Adult↗

Lower-dose (13)C-urea breath test to detect Helicobacter pylori infection-comparison between infrared spectrometer and mass spectrometry analysis.

BACKGROUND: The expense of the (13)C-urea breath test (UBT) to detect Helicobacter pylori infection is mainly due to the cost of (13)C-urea and the analysis using isotope ratio mass spectrometry (IRMS). AIM: To test whether a UBT, using a lower dose of urea and lower-priced isotope-selective nondispersive infrared spectrometry (INIS), can preserve diagnostic efficacy in clinical practice. METHODS: A total of 177 dyspeptic patients received endoscopy for H. pylori culture and histology. All of them received a UBT in which the duplicate baseline, 10 min, and 15 min breath samples after ingestion of 50 mg (13)C-urea were collected to analyse the excess (13)CO(2)/(12)CO(2) ratio (ECR) by IRMS (ABCA, Europa Scientific, UK) and INIS (UBiT-IR200, Photal Otsuka Electronics, Japan), respectively. RESULTS: Of the 177 patients, 84 were infected and 93 were uninfected with H. pylori. A close correlation of ECR was found between IRMS and INIS (r=0.9829 at 10 min; r=0.9918 at 15 min, P < 0.0001). Analysing the 15-min samples, UBT by both IRMS and INIS achieved the same sensitivity (96. 4%) and specificity (98.9%). CONCLUSIONS: INIS is as effective as IRMS for UBT, and can use a lower dose of (13)C-urea. This can provide an economic UBT, using the lower-priced INIS and a low dose of (13)C-urea.

Adult↗

Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model.

PURPOSE: To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. MATERIAL AND METHODS: Forty rats of both sexes were randomly divided into 5 groups (n=8/group) and glycerine for inducing renal failure was given to all rats except controls. RESULTS: In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. CONCLUSION: The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Acute Kidney Injury↗

A phase II trial of tamoxifen, ifosfamide, epirubicin, and cisplatin combination chemotherapy for inoperable non-small-cell lung cancer.

A phase II trial of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy was conducted in patients with chemonaive inoperable non-small-cell lung cancer (NSCLC) to assess response and toxicity. From October 1997 to August 1998, 19 patients were treated. The treatment schema included tamoxifen 60 mg twice daily by mouth on days 1 to 3, ifosfamide 3 g/m2 intravenous infusion (IV) 60 minutes with mesna on day 2, epirubicin 50 mg/m2 IV bolus on day 2, and cisplatin 60 mg/m2 IV 60 minutes on day 2 every 4 weeks for up to six cycles. All patients were evaluable for response and toxicity. The major toxicity was myelosuppression; grade 3 or 4 leukopenia or neutropenia occurred in 14 of 19 (73.7%) patients during treatment, and 6 patients (31.6%) experienced fever in association with the neutropenia; no toxic deaths occurred. Grade 3 anemia occurred in six patients (31.6%) during the treatment. Grade 3 or 4 nausea/vomiting occurred in only one patient. Toxicities other than neutropenia and anemia were minimal. After two cycles of treatment, 9 of 19 patients attained a partial response (47.4%, 95% confidence interval 24.9%-69.9%) in this study. The median time to disease progression was 6 months and median survival time was 12 months. We conclude that TIEP is an active combination regimen with an acceptable toxicity profile in Chinese patients with inoperable NSCLC.

Aged↗