Biomedical subjects

K Wang

Publications and source records attributed to K Wang.

At least 253 records · Page 14Linked to original sources

PubMed1999

Characteristics and risk factors of acetaminophen-induced hepatitis in Taiwan.

BACKGROUND: Overdose of acetaminophen may cause hepatic injury and fatal fulminant hepatic failure. Acetaminophen is the most common form of drug-induced hepatic injury in Western countries. However, there is no formal report of this important issue in Taiwan. To assess the clinical characteristics and risk factors of acetaminophen-induced hepatitis in Taiwan, we conducted this study. METHODS: A total of 71 patients who were intoxicated or overdosed with acetaminophen at Veterans General Hospital-Taipei between February, 1991 and June, 1997 were enrolled in this study. Acetaminophen-induced hepatitis was defined according to the Paris international consensus criteria. RESULTS: Suicide attempt was the major cause (67/71) of acetaminophen overdose. Sixty-two of the patients were female. The mean patient age was 24.5 +/- 9.7 years (+/- standard deviation, SD). Nineteen of 71 patients had acetaminophen-induced hepatitis. The peak serum alanine aminotransferase, aspartate aminotransferase and total bilirubin concentrations were 4,181.0 +/- 931.4 IU/l (mean +/- SD), 4,148.0 +/- 1,147.5 IU/l and 2.6 +/- 0.4 mg/dl, respectively. The hepatitis group had higher ingested acetaminophen doses and serum peak acetaminophen levels than did those of the nonhepatitis group (24.9 g vs 12.9 g, p = 0.004; 132.0 mg/l vs 61.7 mg/l, p = 0.013). A higher percentage of alcohol consumption was also noted in the hepatitis group than in the nonhepatitis group (32% vs 12%, p = 0.05). After logistic regression for multivariate analysis, alcohol consumption was the most important risk factor for acetaminophen-induced hepatitis (odds ratio = 8.14, p = 0.018), followed by ingested acetaminophen dose (odds ratio = 1.21, p = 0.001). Most patients received acetylcysteine treatment in time. Two of the 19 patients with hepatitis died. CONCLUSIONS: The majority of acetaminophen-induced hepatitis in Taiwan occurs in young females who attempt suicide. Alcohol consumption and the dose of acetaminophen ingested were the significant risk factors for acetaminophen-induced hepatitis. Alcohol should not be concomitantly used with acetaminophen. Early diagnosis and administration of the antidote are crucial to decrease mortality.

Acetaminophen↗

PubMed1999

Life-threatening toxicity in a dihydropyrimidine dehydrogenase-deficient patient after treatment with topical 5-fluorouracil.

In humans, 80-90% of an administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD; EC 1.3.1.2), the initial rate-limiting enzyme in pyrimidine catabolism. Cancer patients with decreased DPD activity are at increased risk for severe toxicity including diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity, and, in some cases, death. We now report the first known cancer patient who developed life-threatening complications after treatment with topical 5-FU and was shown subsequently to have profound DPD deficiency. RT-PCR and genomic PCR methodologies were used to identify a G to A mutation in the GT 5' splicing recognition sequence of intron 14, resulting in a 165-bp deletion (corresponding to exon 14) in this patient's DPD mRNA. Immunoprecipitation and Western blot analysis were then used to demonstrate that the aberrant DPD mRNA is translated into a nonfunctional DPD protein that is ubiquitinated. We conclude that the presence of this metabolic defect combined with topical 5-FU (a drug demonstrating a narrow therapeutic index) results in the unusual presentation of life-threatening toxicity after treatment with a topical drug. These data further suggest that degradation by the ubiquitin-proteosome-mediated system plays a role in the elimination of the DPD protein.

Aged↗

PubMed1999

Neointimal hyperplasia and late pathologic remodeling in a porcine coronary stent model.

BACKGROUND: Although coronary stenting has been demonstrated to significantly reduce restenosis compared to conventional angioplasty, occurrence of in-stent stenosis still remains one of the major limitations. This study investigates the influence of stent strut diameter on injury, inflammatory response, thrombosis and neointimal hyperplasia in a porcine coronary artery. METHODS: Coil stents made of either a 0.12 mm, 0.15 mm or 0.18 mm wire were randomly implanted in the right coronary arteries of 30 pigs. Quantitative coronary angiography analysis was performed before, immediately after, and 6 weeks following the stenting procedure. At 6 weeks, histopathology for evaluation of injury, thrombosis and inflammation, as well as morphometry for calculation of the neointimal hyperplasia and internal elastic lamina area were performed. RESULTS: Quantitative coronary analysis showed similar quantitative data before and after stent placement in the three groups. At 6 weeks, however, a significantly bigger MLD was found in the 0.18 mm group. Morphometric analysis at 6 weeks confirmed these results, showing a significantly bigger lumen area in both the 0.18 mm (1.71 +/- 0.66 mm2) and 0.15 mm (1.36 +/- 0.53 mm2) groups compared to the 0.12 mm group (0.71 +/- 0.38 mm2). The calculated neointimal hyperplasia was similar in the three groups (0.12 mm: 1.93 +/- 0.51 mm2; 0.15 mm: 1.68 +/- 0.63 mm2; and 0.18 mm: 2.16 +/- 1.48 mm2). The internal elastic membrane area, however, was significantly bigger in the 0.18 mm (3.87 +/- 1.39 mm2) compared to the 0.12 group (2.65 +/- 0.53 mm2). CONCLUSION: These results suggest that pathologic remodeling can also play an important role in late lumen loss after stent implantation.

Animals↗

PubMed1999

[Effect of selective lesions in hypothalamus on bilateral synchronized bursts of rat oxytocin neurons].

In order to clarify the location of the center for synchronized milk-ejection bursts of magnocellular oxytocin neurons in the hypothalamus, the bursts of these neurons were recorded extracellularly in lactating rats with selectively-cutting lesions of the middle brain or hypothalamus. Results showed that unilateral transection of the middle midbrain above the ventral tegmentum did not block the synchronized bursts on both sides; however, the synchronized bursts disappeared after unilateral transection through the middle of the medial hypothalamus. These results suggest that the area from the middle part of the midbrain to that of the hypothalamus does play a crucial role in the synchronized milk-ejection burst.

Animals↗

PubMed1999

[Clone and tissue expression of tree shrew apolipoprotein AI cDNA].

OBJECTIVES: To clone apolipoprotein AI (apoAI) gene from tree shrew (TS) which is an animal insusceptible to atherosclerosis and to analyze the characteristics of the gene. METHODS: A cDNA library of the liver tissue was constructed by using the isolated mRNA as the template during reverse transcription. The positive clones of apoAI cDNA were identified in the library with an anti-serum to TS apoAI. Sequencing, analyzing and expressing of the clones were finished. RESULTS: A complete cDNA sequence of TS apoAI was determined as 900 nucleotides. It contained 28 bp in 5' untranslated region, and 795 bp in an open reading frame encoding a 265-amino acid apoAI precursor (an 18-amino acid signal peptide, a 6-amino acid propeptide and a 241-amino acid mature protein), two stop codens (TGA, TAA) and following 72 bp in 3' untranslated region. The novel gene was submitted to GenBank. TS apoAI deduced from the cDNA sequence was more hydrophobic than that of human. The results of Northern blot indicated the plentiful presence of apoAI mRNA in TS liver and intestine. CONCLUSIONS: A new gene was cloned from TS, one animal insusceptible to atherosclerosis. TS apoAI may have a stronger activity of binding cholesterol and cholesterol ester than that of human apoAI in reverse cholesterol transport. A good foundation was laid for studying the molecular structure and function of TS apoA I.

Amino Acid Sequence↗

PubMed1999

[The immunohistochemical changes of TGF-beta, type I and III collagen in corneal healing after photorefractive keratectomy].

OBJECTIVE: To observe the immunohistochemical expression of transforming growth factor-beta (TGF-beta), type I and III collagen in monkey corneal healing after photorefractive keratectomy (PRK) and find whether TGF-beta is involved in the process of corneal healing and correlated with the syntheses of type I and III collagen. METHODS: Three rhesus monkeys (6 eyes) were operated for myopic ablation of 10.0 diopters. The depth of ablation was 103 microm. Microscopy, transmission electron microscopy and immunohistochemistry were performed at 1, 3 and 6 months after PRK. RESULTS: TGF-beta staining was positive in the epithelium and a few fibroblasts under the epithelium at one month after the operation. The staining was negative at 6 months and in the control specimens. Postoperatively, type I and III collagen stainings were evident at 1, 3 and 6 months. Type I collagen staining was positive and type III was negative in the controls. CONCLUSION: TGF-beta is involved in the corneal healing after PRK, and perhaps correlated with the syntheses of type I and III collagen.

Animals↗

PubMed1999

[Analysis of intraocular pressure and corneal thickness after laser in situ keratomileusis].

OBJECTIVE: To analyze the changes and relationship of the intraocular pressure (IOP) and the corneal thickness (CT) after laser in situ keratomileusis (LASIK). METHODS: This prospective study comprised two groups: noncontact tonometer group 221 eyes (156 patients) 1 month after LASIK and 72 eyes (50 patients) 3 months after LASIK; Goldmann applanation tonometer group 60 eyes (36 patients) 1 month after LASIK. The spherical equivalent, the corneal thickness and the IOP readings were measured pre- and post-LASIK. RESULTS: The CT was thicker than the predicted value and it was much more prominent in the higher myopic group with more regression degree of refraction. The CT at postoperative 3 month was thicker than that at 1 month. There was a statistical decrease in mean tonometer readings, both with non-contact tonometer and Goldmann applanation tonometer; and there was statistically significant correlation between the changes of central corneal thickness and the changes of non-contact tonometer readings (r = 0.2, P < 0.002). The IOP decrease with Goldmann applanation tonometer was less than that with noncontact tonometer. CONCLUSIONS: The actual ablation depth of cornea is lower than the predicted. The IOP readings of the patients after LASIK are lower than the real IOP values. Further efforts should be made to improve the accuracy. Goldmann applanation tonometer is a better choice measuring IOP after excimer photoablative corneal refractive surgery.

Adolescent↗

PubMed1999

[Study of cleft palate with problems of middle ears and its treatment].

OBJECTIVE: To gain a clear idea of the following: 1. the relationship between the incidence of functional obstruction of middle ear and surgery on cleft palate and patients' age; 2. the bacterial culture of secretion taken from the tympanic cavity with secretory otitis media; 3. the preliminary effects of treatment by inserting a tube into the tympanic cavity of a patient with secretory otitis media. METHODS: 275 middle ears of patients with cleft palate were selected, then acoustic immitence examination and hearing threshold of pure tone were adopted, and bacterial culture was carried out for studying secretion of the middle ear with secretory otitis media. RESULTS: The tympanograms of 75.5% ears of the patients before cleft palate operation were found to be abnormal, among which patients under 3 years were 81%, and 41.2% ears of those after closure of cleft palate were abnormal. Gram's positive and negative germs of bacterial culture were 20.1% and 24% respectively. The hearing of 6 ears with secretory otitis media has recovered from the moderate hearing loss due to tube insertion. And the tympanograms of 4/8 ears were transformed from type B to type A. CONCLUSION: It is beneficial to improve function of Eustachian tube if cleft palate can be repaired at an early stage and beneficial to improve the patients' hearing and devlope their speech if a tube is inserted into the typanic cavity in cases of secretory otitis media at an early stage.

Adolescent↗

PubMed1999

[The development of mouse bioreactor expressing human tissue plasminogen activator (tPA) in mammary gland by transfecting spermatozoa in testicular duct].

The most established methods for development of transgenic animals are the microinjection of DNA into the fertilized eggs, but it is still a procedure of certain complexity and high cost. Therefore, the idea of using sperm as a vehicle to carry exogenous DNA into eggs is very attractive, and there have been some successful reports. Though the methods are rather simple they sometimes have low reproducibility. To improve the technique we transinfected the spermatozoa in testicular duct, not in vitro, to produce mice which expressed human tissue plasminogen activator (tPA) in mammary gland. The results demonstrated that: (1) 5 transinfected mice mated 10 female mice in 10 days after operation, (2) 79 founders were developed and 42 survived, (3) using PCR to detect foreign DNA integrated into the genome of founders, 7 out of 42 founders were positive (16.67%), (4) The expression level of tPA was 48-80 ng/ml in the milk of 5 PCR positive founders and (5) the foreign DNA integrated into the genome was detected in 2 out of 4 1st offspring by PCR technique.

Animals↗

PubMed1999

[Chemical constituents of Scolopendra negrocapitis].

The chemical constituent of Scolopendra negrocapitis Zhang et Wang were systematically analyzed and compared with S. subspinipes mutilans L. Koch. The results showed the lipid content was 18.7%, protein was 63.4% and total amino acid was 11.9%; S. negrocapitis contained the same twelve fat acids (the content of unsaturated fat acid was nearly 64% in its fat acids), twenty one amino acids and twelve trace elements as S. subspinipes mutilans had. The protein of S. negrocapitis showed forteen bands as determined by polyacrylamide gel electrophoresis. S. negrocapitis and S. subspinipes mutilans have the same main chemical composition. The contents of compositions are different. S. negrocapitis is worth as the nature resources of medicinal centepede.

Amino Acids↗

PubMed1999

[The preliminary study of amniotic membrane on TGF-beta 1 expression after photorefractive keratectomy].

OBJECTIVE: To investigate the effect of amniotic membrane on TGF-beta 1 expression after photorefractive keratectomy(PRK). METHODS: PRK was performed bilaterally on 6 New Zealand white rabbits. One eye was randomly tranplanted with preserved human amniotic membrane, and the other eye served as the control. The expression of TGF-beta 1 mRNA was detected with in situ hybridization at the 4th weeks after PRK. RESULTS: TGF-beta 1 mRNA expression was present in the corneal epithelium and stroma at the 4th weeks after PRK. The cornea in amniotic membrane transplanted group had also TGF-beta 1 mRNA expression, and the expression extent was less than that in control group (P < 0.05). CONCLUSION: Amniotic membrane can reduce the expression of TGF-beta 1 mRNA in cornea after PRK.

Amnion↗

PubMed1998

Mapping the subsite preferences of protein tyrosine phosphatase PTP-1B using combinatorial chemistry approaches.

Protein tyrosine phosphatases (PTPases) are important regulators of signal transduction systems, but the specificity of their action is largely unexplored. We have approached this problem by attempting to map the subsite preferences of these enzymes using combinatorial chemistry approaches. Protein-tyrosine peptidomimetics containing nonhydrolyzable phosphotyrosine analogues bind to PTPases with high affinity and act as competitive inhibitors of phosphatase activity. Human PTP-1B, a PTPase implicated to play an important role in the regulation of growth factor signal transduction pathways, was used to screen a synthetic combinatorial library containing malonyltyrosine as a phosphotyrosine mimic. Using two cross-validating combinatorial chemistry screening approaches, one using an iterative method and the other employing library affinity selection-mass spectrometric detection, peptides with high affinity for PTP-1B were identified and subsite preferences were detailed by quantitatively comparing residues of different character. Consistent with previous observations, acidic residues were preferred in subsites X-3 and X-2. In contrast, aromatic substitutions were clearly preferred at the X-1 subsite. This information supports the concept that this class of enzymes may have high substrate specificity as dictated by the sequence proximal to the phosphorylation site. The results are discussed with regards to the use of combinatorial techniques in order to elucidate the interplay between enzyme subsites.

Computer Simulation↗

PubMed1998

Single electron reduction of cytochrome c oxidase compound F: resolution of partial steps by transient spectroscopy.

The final step of the catalytic cycle of cytochrome oxidase, the reduction of oxyferryl heme a3 in compound F, was investigated using a binuclear polypyridine ruthenium complex (Ru2C) as a photoactive reducing agent. The net charge of +4 on Ru2C allows it to bind electrostatically near CuA in subunit II of cytochrome oxidase. Photoexcitation of Ru2C with a laser flash results in formation of a metal-to-ligand charge-transfer excited state, Ru2C, which rapidly transfers an electron to CuA of cytochrome oxidase from either beef heart or Rhodobacter sphaeroides. This is followed by reversible electron transfer from CuA to heme a with forward and reverse rate constants of k1 = 9.3 x 10(4) s-1 and k-1 = 1.7 x 10(4) s-1 for R. sphaeroides cytochrome oxidase in the resting state. Compound F was prepared by treating the resting enzyme with excess hydrogen peroxide. The value of the rate constant k1 is the same in compound F where heme a3 is in the oxyferryl form as in the resting enzyme where heme a3 is ferric. Reduction of heme a in compound F is followed by electron transfer from heme a to oxyferryl heme a3 with a rate constant of 700 s-1, as indicated by transients at 605 and 580 nm. No delay between heme a reoxidation and oxyferryl heme a3 reduction is observed, showing that no electron-transfer intermediates, such as reduced CuB, accumulate in this process. The rate constant for electron transfer from heme a to oxyferryl heme a3 was measured in beef cytochrome oxidase from pH 7.0 to pH 9.5, and found to decrease upon titration of a group with a pKa of 9.0. The rate constant is slower in D2O than in H2O by a factor of 4.3, indicating that the electron-transfer reaction is rate-limited by a proton-transfer step. The pH dependence and deuterium isotope effect for reduction of isolated compound F are comparable to that observed during reaction of the reduced, CO-inhibited CcO with oxygen by the flow-flash technique. This result indicates that electron transfer from heme a to oxyferryl heme a3 is not controlled by conformational effects imposed by the initial redox state of the enzyme. The rate constant for electron transfer from heme a to oxyferryl heme a3 is the same in the R. sphaeroides K362M CcO mutant as in wild-type CcO, indicating that the K-channel is not involved in proton uptake during reduction of compound F.

2,2'-Dipyridyl↗

PubMed1998

BID, a proapoptotic BCL-2 family member, is localized to mouse chromosome 6 and human chromosome 22q11.

BID is a proapoptotic member of the BCL-2 family of cell death regulators. BID shares sequence homology with other members of the family within a single alpha-helical domain, BH3. BH3 is required for BID to interact with BCL-2 and BAX, as well as for its function as a death agonist. We have isolated and characterized mouse Bid and human BID genomic clones. The sequence for BID is encoded within five exons. We used interspecific backcross analysis to localize Bid to the distal region of mouse chromosome 6 near the Atp6e locus. Fluorescence in situ hybridization analysis localized human BID to a syntenic human region, chromosome 22q11, close to the BCR-1 gene.

Animals↗

PubMed1998

Prostaglandin E2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness.

Regulation of the factors governing IL-12R expression and IL-12 responsiveness has been shown to be important in the generation and stability of Th1- and Th2-type responses. In this regard, cytokines have been shown to have a prominent role in regulating IL-12R expression. In this study, the role that PGE2 and dexamethasone (DXM) have in regulating IL-12R expression was evaluated. Addition of PGE2 or DXM to human PBMCs stimulated with immobilized anti-CD3 plus IL-12 inhibited the production of IFN-gamma in a dose-responsive manner. Moreover, PBMCs stimulated with immobilized anti-CD3 in the presence of PGE2 or DXM for 3 days, washed extensively, and restimulated in the presence of IL-12 still did not produce IFN-gamma. This lack of IL-12 responsiveness from cells cultured in either PGE2 or DXM was correlated with diminished surface expression of IL-12Rbeta1, IL-12Rbeta2 mRNA expression, and IL-12 binding. Finally, the PGE2- and DXM-mediated inhibition of IL-12R expression was not affected significantly by addition of neutralizing Abs against either IL-4, IL-10, or TGF-beta. By contrast, addition of dibutyryl cAMP, 8-bromoadenosine 3:5 cAMP (8-Br-cAMP), or cholera toxin substantially reduced IL-12R expression, suggesting that PGE2 may be mediating its effects through enhancement of cAMP.

Cells, Cultured↗

PubMed1998

Hematopoietic malignancies demonstrate loss-of-function mutations of BAX.

The BCL-2 gene family regulates the susceptibility to apoptotic cell death in many cell types during embryonic development and normal tissue homeostasis. Deregulated expression of anti-apoptotic BCL-2 can be a primary aberration that promotes malignancy and also confers resistance to chemotherapeutic agents. Recently, studies of Bax-deficient mice have indicated that the pro-apoptotic BAX molecule can function as a tumor suppressor. Consequently, we examined human hematopoietic malignancies and found that approximately 21% of lines possessed mutations in BAX, perhaps most commonly in the acute lymphoblastic leukemia subset. Approximately half were nucleotide insertions or deletions within a deoxyguanosine (G8) tract, resulting in a proximal frame shift and loss of immunodetectable BAX protein. Other BAX mutants bore single amino acid substitutions within BH1 or BH3 domains, demonstrated altered patterns of protein dimerization, and had lost death-promoting activity. Thus, mutations in the pro-apoptotic molecule BAX that confer resistance to apoptosis are also found in malignancies.

Animals↗

PubMed1998

A conserved sequence block in murine and human T cell receptor (TCR) Jalpha region is a composite element that enhances TCR alpha enhancer activity and binds multiple nuclear factors.

A conserved sequence block (CSB) located in a noncoding region of the mouse and human TCR alpha/delta loci, showing six differences over 125 nucleotide positions (95% similar), was subjected to detailed analyses in this study. Transient transfection results showed that the CSB-containing element in conjunction with the TCR alpha enhancer up-regulated the alpha enhancer activity, whereas no enhancer activity was detected when CSB alone was assayed. In vitro occupancy analyses of CSB by nuclear factors reveal the existence of an unexpectedly intricate network of CSB-protein and protein-protein interactions. Lymphoid-specific as well as T-lineage-specific nuclear factors are involved to differentially form CSB-bound complexes in extracts of various tissues and cell lines. Liver was shown to contain factor(s) sequestering thymic CSB-binding factors. Furthermore, the putative binding sites for transcription factors known to be important for lymphoid-lineage development are present in CSB and are targeted by nuclear factors. On the basis of these results, we propose that the CSB element may play a role in shaping the chromatin structure by which the accessibility of TCR alpha/delta loci to the recombinase complex and/or to the transcriptional apparatus can be controlled.

Animals↗

PubMed1998

2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease.

A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by beta-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).

Complement C1r↗