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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 1,117 records · Page 62Linked to original sources
PubMedDate not supplied

Formation of acyclic and cyclic guanine adducts in DNA reacted with alpha-acetoxy-N-nitrosopyrrolidine.

This paper describes the reaction of alpha-acetoxy-N-nitrosopyrrolidine with DNA to produce six adducts: two new acyclic adducts, 7-(4-oxobutyl)guanine (6) and 7-(3-carboxypropyl)guanine (7), and four cyclic adducts--the exocyclic 7,8-guanine adducts 5, 11, and 12 and an exocyclic 1,N2-guanine adduct 13--which we have previously characterized. The initial purpose of this study was to carry out an independent synthesis to verify the structure of adduct 5, which is formed in liver DNA of rats treated with N-nitrosopyrrolidine. This was accomplished by the reaction of 2',3',5'-triacetylguanosine with 4-iodobutyraldehyde. This reaction also produced 7-(4-oxobutyl)guanine (6), which underwent air oxidation to 7. The new adducts were characterized by their proton NMR, UV, and mass spectral properties, by chemical transformations, and by independent syntheses. The six adduct standards were used to develop HPLC systems for their analysis as products of the reaction of alpha-acetoxy-N-nitrosopyrrolidine with DNA. Studies on their rates of formation and stability in DNA were carried out. The major products were 7-(4-oxobutyl)guanine (6) and the exocyclic 7,8-guanine adduct 5, which apparently were both formed mainly by reaction with DNA of 4-oxobutanediazohydroxide (4). Their concentrations were maximal after 6 h and subsequently decreased due to depurination. Little evidence was obtained for cyclization of 6 to 5, at the base level or in DNA. The concentrations of adducts 11-13, which were formed by reaction with DNA of crotonaldehyde (10), increased gradually over the 36-h time period studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Differential effects of thiols on DNA modifications via alkylation and Michael addition by alpha-acetoxy-N-nitrosopyrrolidine.

The hepatocarcinogen NPYR is metabolically activated by alpha-hydroxylation mediated by cytochrome P-450 enzymes to yield a 4-oxobutylating agent and 2-butenal (crotonaldehyde). Both are reactive intermediates capable of modifying DNA with guanine either by simple alkylation or by Michael type addition, respectively. In order to assess the roles of these pathways in NPYR tumorigenesis, we are interested in identifying agents which can selectively modify one of these two pathways. In this study, we examined the effects of three thiols--(mesna), glutathione (Glu), and N-acetylcysteine (Nac)--on DNA adduct formation by alpha-acetoxyNPYR, a stable precursor of alpha-hydroxyNPYR. Calf thymus DNA isolated from incubation of alpha-acetoxyNPYR with or without thiol was hydrolyzed and analyzed for the adducts formed by alkylation (adducts 1 and 2) and Michael addition (adducts 3-5). The results showed that the addition of mesna completely blocked the formation of the crotonaldehyde-derived adducts 3-5, whereas it exerted little effect on the formation of the alkylated adducts 1 and 2. These results indicate the preferential conjugation of mesna with crotonaldehyde. In contrast, Nac had little selectivity on adduct formation; levels of adducts 1 to 5 were were reduced by 36-75%. These results suggest that Nac conjugated with both alkylating agent and crotonaldehyde. Similar to mesna, Glu blocked the formation of the crotonaldehyde-derived adducts (adducts 3-5) efficiently. However, unlike mesna, Glu inhibited the formation of adduct 1, while it did not inhibit the formation of adduct 2, although both adducts are presumably derived from the 4-oxobutylating agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
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Formation of the acrolein-derived 1,N2-propanodeoxyguanosine adducts in DNA upon reaction with 3-(N-carbethoxy-N-nitrosamino)propionaldehyde.

3-(Methylnitrosamino)propionaldehyde (MNPA) is a carcinogenic nitrosamine formed by nitrosation of arecoline, a major alkaloid in areca nut which is a constituent of betel quid. While DNA adducts of its analogue, 3-(methylnitrosamino)propionitrile, have been characterized, little is known about the structures of DNA adducts by MNPA. In this paper, we report that the acrolein-derived 1,N2-propanoguanine adducts are formed upon incubating deoxyguanosine or DNA with 3-(N-carbethoxy-N-nitrosamino)propionaldehyde, a stable carbamate precursor of the metabolically activated MNPA. The identities of these adducts were confirmed by HPLC co-migration, by their NMR and UV spectra, and by chemical properties as compared with those of the synthetic standards. Analogous results were obtained from the reaction of the carbamate with calf thymus DNA. Upon acid or enzyme hydrolysis of the carbamate-modified DNA, acrolein-guanine adducts were detected, and the levels were quantitated. Again, the identities of the adducts were verified by co-chromatography with the standards, by UV spectroscopy, or by the ring-opening with NaOH/NaBH4. Consistent with its ability to modify DNA, the carbamate was found to be mutagenic in Salmonella tester strains. These results show that acrolein is a likely metabolite from the activation of MNPA and that the formation of 1,N2-propanoguanine adducts may contribute to the mutagenicity of the carbamate of MNPA.

Acrolein↗
PubMedDate not supplied

Manufacture and evaluation of bioactive and biodegradable materials and scaffolds for tissue engineering.

For tissue regeneration and tissue engineering applications, a number of bioactive and biodegradable composites, either porous or non-porous, were fabricated. The newly developed materials included tricalcium phosphate reinforced polyhydroxybutyrate and its copolymer, poorly crystallized hydroxyapatite reinforced chitin, and plasma sprayed hydroxyapatite reinforced poly(L-lactic acid). It was shown that these new materials could be successfully produced using the manufacturing techniques adopted. In vitro experiments revealed that the incorporation of bioceramic particles in biodegradable polymers rendered the composites bioactive and significantly improved the ability of composites to induce the formation of bone-like apatite on their surfaces. Degradation of composite scaffolds in simulated body fluid was observed and could be due to the simultaneous degradation of polymer matrix and dissolution of bioceramic particles.

Journal Article↗
PubMedDate not supplied

Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in growth suppression of head and neck squamous cell carcinoma cell lines.

E2F-1, a transcription factor by discovery, is thought to play a crucial role in regulating G1/S cell cycle progression. Its activity is modulated by complex formation with the retinoblastoma protein and related proteins. Overexpression of E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines harbor p53 mutations but express different levels of the retinoblastoma protein. Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F-1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter construct containing an E2F-1 binding motif. In vitro growth assay demonstrated that growth suppression by the E2F-1 protein was effective on both cell lines. Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in nude mice showed total suppression of tumor growth at sites that received cells infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing animals. These data indicate that overexpression of E2F-1 via an adenoviral vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma cell lines through induction of apoptosis.

Adenoviridae↗
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Toward assessing family outcomes of service delivery: validation of a family quality of life survey.

BACKGROUND: The concept of family quality of life (QoL) has emerged as an important outcome of service delivery for individuals with disabilities and their families. The present study describes the process of developing a tool to measure family QoL. METHODS AND RESULTS: A total of 1197 respondents participated in a national field test. Through factor analysis, the survey was refined in several ways: (1) the preliminary 10-domain structure was reduced to a five-domain structure; (2) a total of 41 items were selected for the revised survey; and (3) wordings were clarified. CONCLUSIONS: The implications for future research and practice are discussed.

Adolescent↗
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Pulmonary function of nonsmoking female asbestos workers without radiographic signs of asbestosis.

Researchers disagree about whether exposure to asbestos causes significant respiratory impairments and airway obstruction in the absence of radiographic asbestosis and smoking. To obtain confirmatory information, the authors examined pulmonary function of 208 nonsmoking female asbestos workers who did not have asbestosis and 136 controls. The authors observed an overall lower single-breath carbon monoxide diffusing capacity in the asbestos workers than in controls. In addition, significant decreases in percentage vital capacity, percentage forced vital capacity, and percentage mean forced expiratory flow during the middle half of the forced vital capacity were evident in the older workers. Logistic regression analysis revealed that asbestos exposure was associated with abnormal single-breath carbon monoxide diffusing capacity, vital capacity, and mean forced expiratory flow during the middle half of the forced vital capacity among the older workers. The age-related decline in vital capacity, forced vital capacity, and mean forced expiratory flow during the middle half of the forced vital capacity was significantly greater in the asbestos workers than the controls. The findings imply that asbestos-exposure per se contributes predominantly to restricted lung volume and reduced single-breath carbon monoxide diffusing capacity. Asbestos may also cause slight airway obstruction, especially in workers who are heavily exposed.

Adult↗
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Zinc arginine, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight and DNA without affecting testicular function.

Zinc has been implicated in steroid endocrinology of the prostate gland; and 5 alpha-dihydrotestosterone (DHT) is believed to express androgenic responses in the prostate. To note the effect of neutralized zinc (zinc gluconate + arginine) on the prostate, 50 sexually mature rats, weighing 325 +/- 20 g, were divided into five groups as follows: (1) control, (2) sham, (3) castrated, and injected intraprostatically with (4) 10 mg neutralized zinc, and (5) 20 mg neutralized zinc. Results indicated significant reduction (P < 0.05) of prostate weight, 5 alpha-reductase activity, and total protein and DNA concentrations in treated prostate tissue; no significant change in weight and histological structure of testes, epididymides, and seminal vesicles; and no significant effect on progeny and blood testosterone level of treated animals. These results suggest that direct application of neutralized zinc to the prostate offers a new modality for treatment of prostatitis without affecting spermatogenesis.

5-alpha Reductase Inhibitors↗
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Identification of the translocating bacteria in rats with acute liver injury and their relation to the bacterial flora of the intestinal mucosa.

The bacterial flora of the intestine and the bacteria found in liver, mesenteric lymph nodes, portal and arterial blood after D-galactosamine-induced liver injury, with and without pretreatment with Lactobacillus plantarum DSM 9843, were studied in the rat. Dominating representatives were identified to species level by 16S rDNA sequencing and typed by randomly amplified polymorphic DNA (RAPD) and by restriction endonuclease analysis (REA) for strain definition. It was proven that bacterial strains from the intestine occur at extraintestinal sites after liver injury. Lactobacillus spp. dominated the intestinal flora and were also the most frequently found genus in the liver and the mesenteric lymph nodes. Some of the blood isolates, identified as Staphylococcus aureus, Proteus vulgaris and Bacteroides merdae, were not found as a dominating part of the mucosal flora. Treatment with L. plantarum before liver injury decreased translocation and made the intestinal flora increasingly dominated by lactobacilli.

Acute Disease↗
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Effects of melatonin on hypothalamic gamma-aminobutyric acid, aspartic acid, glutamic acid, beta-endorphin and serotonin levels in male mice.

Effects of melatonin on hypothalamic neurotransmitters in male mice were studied. Exogenous melatonin administered intraperitoneally significantly increased (p < 0.05) hypothalamic concentrations of aspartic acid and gamma-aminobutyric acid by over 29 and 50% respectively. Conversely, hypothalamic beta-endorphin concentration was significantly decreased (p < 0.05) 30 min after melatonin administration with doses between 5- and 100 micrograms/kg. Similarly, melatonin, at a concentration of 100 micrograms/kg, decreased (p < 0.05) the serotonin level in mouse hypothalamus by 46%. Melatonin, however, did not affect the concentration of hypothalamic glutamic acid over a dose range of 0.5-300 micrograms melatonin/kg. Our findings suggested that actions of pineal melatonin in animals such as inhibition on serum corticosterone levels might be mediated by the potentiation of activities of hypothalamic neurons containing gamma-aminobutyric acid and aspartic acid or by the inhibition of the beta-endorphin and serotonin hypothalamic neurons. The neurons containing glutamic acid in the hypothalamus were, however, not influenced by melatonin. Our results are in line with the suggestion that melatonin actions on adrenal corticosterone release or other endocrine secretions may be mediated by way of its actions on hypothalamic neurotransmitter activities.

Animals↗
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Reverse transcriptase polymerase chain reaction on fine needle aspirates for rapid detection of translocations in synovial sarcoma.

OBJECTIVE: To evaluate the utilization of fine needle aspiration (FNA) biopsy to obtain material for reverse-transcriptase polymerase chain reaction (RT-PCR) in the detection of the t(X;18)(p11.2;q11.2) translocation in synovial sarcomas. STUDY DESIGN: We applied RT-PCR to detection of synovial sarcoma fusion gene transcripts on fine needle aspirates. Five clinical samples were first analyzed: one was a tumor previously diagnosed as malignant hemangiopericytoma, one was a poorly defined tumor, and three were suspected synovial sarcomas. FNA material was transferred directly to the RT-PCR reaction tube without RNA extraction. RESULTS: The t(X;18) translocation could be detected on the limited amount of material that FNA provides. In each of the cases studied the representivity of the tumor samples was confirmed microscopically. CONCLUSION: Our protocol permits analysis directly on representative samples without extraction of RNA. The results imply that RT-PCR offers reliable detection of sarcoma fusion gene transcripts on fine needle aspirates. The procedure, apart from being applicable to outpatients, is rapid and sensitive.

Adolescent↗
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The deltoid muscle origin. Histologic characteristics and effects of subacromial decompression.

The histologic characteristics of the deltoid muscle attachment to nine cadaveric acromia were studied using light microscopy. The deltoid muscle attaches to the anterior and lateral acromion primarily by direct tendinous attachment. The muscle attaches to the dorsal side of the acromion by periosteal fiber attachment. In the specimens studied, a hypothetical acromioplasty of 4 mm would release, on average, 41% of the direct fiber attachment, and a 6-mm acromioplasty would release 69% for all zones examined histologically. The functional and clinical effects of these findings are not known, but the deltoid muscle would be released by arthroscopic acromioplasty in areas where bone is removed.

Acromion↗
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Effective cryopreservation and long-term storage of primary human hepatocytes with recovery of viability, differentiation, and replicative potential.

Despite reports of successful cryopreservation of primary human hepatocytes, existing methods do not produce sufficient recovery of viable cells to meet the needs of basic research or clinical trials of hepatocellular transplantation. We now describe a protocol for efficient cryopreservation of primary human hepatocytes using University of Wisconsin (UW) solution, fetal bovine serum, and dimethyl sulfoxide (DMSO). This method provides > 90% viability of differentiated, primary human hepatocytes 8 mo after cryopreservation as measured by trypan blue exclusion, preserves hepatocyte morphology, liver-specific gene expression (alpha 1 antitrypsin), and replication. The effectiveness of UW solution as a cryopreservative agent suggests that metabolic as well as ultrastructural factors may be important in the effective cryopreservation of primary human hepatocytes. The present method represents an effective protocol for cryopreserving differentiated primary human hepatocytes for research. This method may allow characterization and banking of human hepatocytes for clinical applications, including hepatocellular transplantation and hepatic assist devices.

Cell Differentiation↗
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Extract from Arca granosa L. inhibits proliferation of human tumour cell lines with kidney and lung origin.

Marine organisms are being considered increasingly as sources of anti-tumour agents. The extract from Arca granosa L. has been shown to decrease the growth of tumours and this study was undertaken to determine its ability and mechanism of inhibition. The extract inhibited the proliferation of six human tumour cell lines from different origins with varying sensitivity. The cell lines Ketr-3, A549 and NCl-H460 with kidney or lung origins were more sensitive to the extract than those of the HepG-2, MCF-7 and MGC-803 cells from other origins. In the three sensitive cell lines (Ketr-3, A549 and NCI-H460) the extract was shown to block different phases of the cell cycle progression and inhibit DNA synthesis in a concentration-dependent manner. It was concluded that the extract from A. granosa is potentially a novel anti-tumour agent, especially on kidney and lung tumour cell lines.

Animals↗
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Expression of c-fos protein in serotonergic neurons of rat brainstem following electro-acupuncture.

The c-fos proto-oncogene encodes a nuclear phosphoprotein, Fos which has been proposed to be a "third messenger" coupling short term extracellular signals to long term alteration in cell function. Using double labeling immunocytochemistry, the present work demonstrated the co-localization of Fos protein and serotonin in the nucleus raphe dorsalis, nucleus raphe centralis superior and rostral ventromedial medulla. The results pose an interesting problem, the possible relation of Fos protein to the biosynthesis of serotonin, awaiting further investigation.

Animals↗
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Mu opiate receptor antagonist blocks electroacupuncture inhibition on noxious blood pressure response in rabbits.

A pressor blood pressure response was elicited by strong electric shock stimulation of the front paw in rabbits anesthetized with chloralose and urethane, immobilized by gallamine triethiodide and maintained by artificial ventilation. The pressor response showed a gradual decline in 3-4 successive trials. Naloxone or TCTAP, a specific mu receptor antagonist, administered intraventricularly (icv) at that time could facilitate the pressor response (n = 8, P < 0.02; n = 7, P < 0.01), suggesting the involvement of mu receptors in the declination of the pressor response. Electroacupuncture could inhibit the pressor response (n = 7, P < 0.01), and the inhibition was readily blocked by TCTAP (n = 7, P < 0.01). No obvious changes were observed in the normal saline control group. The results suggest that acupuncture is able to inhibit the pressor response via the activation of the opioid peptidergic system, of which the mu receptor is an important component.

Animals↗
PubMedDate not supplied

Coexistence of Fos protein and proopiomelanocortin mRNA in hypothalamic arcuate nucleus following electroacupuncture.

The immediate early gene, c-fos encodes a nuclear phosphoprotein, Fos which has been proposed to be a third messenger to regulate the expression of specific target genes. The present work demonstrated the coexistence of Fos protein and proopiomelanocortin (POMC) mRNA in the hypothalamic arcuate nucleus (Arc) using techniques of in situ hybridization and immunocytochemistry. The results suggest the activation of beta-endorphinergic (beta-EP) neurons in the Arc by electroacupuncture (EA) and the possible involvement of Fos in modulating POMC expression.

Animals↗