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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 307 records · Page 17Linked to original sources

Value of quantitative analysis of serum cTnT in diagnosis of cardiac disease and myocardial injury.

Serum cTnT, CK-MB and LD1 were measured in 30 patients with AMI, 76 patients with VMC, 12 patients who had undergone operation without cardioplegia, 16 patients who had received open heart operation, 15 patients who had undergone thoracotomy for non-heart surgery and 55 healthy people. Concentration of serum cTnT was 0.057 +/- 0.056 microgram/L in healthy people, 0.069 +/- 0.032 microgram/L in patients who underwent thoracotomy for non-heart surgery, 0.328 +/- 0.472 microgram/L in patients with VMC, 0.388 +/- 0.279 microgram/L in patients with DCM, 4.259 +/- 4.619 micrograms/L in patients with AMI, 8.55 +/- 6.78 micrograms/L in patients who had undergone operation without cardioplegia and 16.03 +/- 6.01 micrograms/L in heart operation patients. In patients with VCM and DCM, serum cTnT was more specific and sensitive than CK-MB and LD1 for diagnosing myocardial injury. In patients with AMI and heart operation patients, the increasing multiple of serum cTnT was obviously higher than that of CK-MB and LD1. 72 h after heart operation, cTnT was still higher than normal, while CK-MB had returned to normal level. Serum cTnT had higher specificity and sensitivity and longer diagnostic period in diagnosing myocardial injury. Moreover, cTnT assay could indicate the degree of myocardial injury. So, quantitative analysis of cTnT can be used as a routine examination in the diagnosis of myocardial injury.

Aged↗

Effects of chronic lead exposure on short-term and long-term depression in area CA1 of the rat hippocampus in vivo.

Chronic developmental lead (Pb) exposure to the rat has been reported to impair the long-term potentiation (LTP) in area CA1 and DG of the hippocampus. The present study was performed to investigate the effects of chronic Pb exposure on homosynaptic short-term depression (STD) and long-term depression (LTD) of population spikes (PS) in area CA1 of the rat hippocampus in vivo. Neonatal Wistar rats were exposed to Pb from parturition to weaning via the milk of dams fed with 0.2% lead acetate solution. The input/output (I/O) function, paired-pulse reaction (PPR), the PS were measured in the area CA1 in response to low frequency stimulation (LFS). The results showed that the homo-STD amplitude of PS depotentiation in Pb-exposed rats (87.48 +/- 7.44%, n = 14) was less significant than that in control rats (72.34 +/- 6.05%, n = 18, P<0.05), and the homo-LTD amplitude of PS depotentiation in Pb-exposed rats (72.80 +/- 5.86%, n = 14) was even less significant than that in control rats (47.80 +/- 5.03%, n = 18, P<0.01). The results suggest that chronic Pb exposure in neonatal rats caused impairments in the STD and LTD of area CA1 of hippocampus.

Animals↗

Estimating a treatment effect with the accelerated hazards models.

In randomized clinical trials, when the outcome of interest is time to event, the proportional hazards model or the accelerated failure time model is often used to identify a treatment effect. In this article, we discuss a simple alternative called the accelerated hazards model in which the treatment effect is characterized as the hazard progression time ratio, when the treatment is believed to accelerate or decelerate the underlying hazard progression through time. Survival data from an actual randomized placebo-controlled trial, which evaluates the effectiveness of biodegradable polymers with carmustine to treat malignant gliomas, is used for illustration.

Antineoplastic Agents, Alkylating↗

Phylogenetic evidence for novel and genetically different intestinal spirochetes resembling Brachyspira aalborgi in the mucosa of the human colon as revealed by 16S rDNA analysis.

Intestinal spirochetes (Brachyspira spp.) are causative agents of intestinal disorders in animals and humans. Phylogenetic analysis of cloned 16S rRNA genes from biopsies of the intestinal mucosa of the colon from two Swedish 60-years old adults without clinical symptoms revealed the presence of intestinal spirochetes. Seventeen clones from two individuals and 11 reference strains were analyzed and the intestinal spirochetes could be divided into two lineages, the Brachyspira aalborgi and the Brachyspira hyodysenteriae lineages. All of the clones grouped in the B. aalborgi lineage. Moreover, the B. aalborgi lineage could be divided into three distinct phylogenetic clusters as confirmed by bootstrap and signature nucleotide analysis. The first cluster comprised 6 clones and the type strain B. aalborgi NCTC 11492T. The cluster 1 showed a 16S rRNA gene similarity of 99.4-99.9%. This cluster also harbored the only other strain of B. aalborgi isolated so far, namely strain W1, which was subjected to phylogenetic analysis in this work. The second cluster harbored 9 clones with a 98.7 to 99.5% range of 16S rDNA similarity to the B. aalborgi cluster 1. Two clones branched distinct and early of the B. aalborgi line forming the third cluster and was found to be 98.7% similar to cluster 1 and 98.3-99.1% to cluster 2. Interestingly, this shows that considerable variation of intestinal spirochetes can be found as constituents of the colonic microbiota in humans, genetically resembling B. aalborgi. The presented data aid significantly to the diagnostic and taxonomic work on these organisms.

Cell Lineage↗

Isolation and structural elucidation of two new glycosides from sage (Salvia officinalis L.).

Six compounds, 1-O-(2,3, 4-trihydroxy-3-methyl)butyl-6-O-feruloyl-beta-D-glucopyranoside, ethyl beta-D-glucopyranosyl tuberonate, p-hydroxybenzoic acid, (-)-hydroxyjasmonic acid, caffeic acid, and 4-hydroxyacetophenone 4-O-[5-O-(3, 5-dimethoxy-4-hydroxybenzoyl)-beta-D-apiofrunosyl]-(1-->2)-beta-D- glu copyranoside, were isolated from the n-butanol-soluble fraction of sage leaf extracts. Their structures were determined by spectral methods (MS, NMR, and 2D-NMR), and their antioxidant activities were measured. Among them, two new glycosides were elucidated. All of these compounds showed DPPH free radical scavenging activity at the concentration of 30 mM, and caffeic acid was the most active compound.

Free Radicals↗

Triterpene glycosides from Cimicifuga racemosa.

Eight new triterpene glycosides named cimiracemosides A-H, respectively, and eight known triterpene glycosides were isolated from the rhizome extracts of black cohosh (Cimicifuga racemosa). The new compounds were determined by spectral data to be 21-hydroxycimigenol-3-O-alpha-L-arabinopyranoside (1), 21-hydroxycimigenol-3-O-beta-D-xylopyranoside (2), cimigenol-3-O-alpha-L-arabinopyranoside (3), 12beta-acetoxycimigenol-3-O-alpha-L-arabinopyranoside (4), 24-acetylisodahurinol-3-O-beta-D-xylopyranoside (5), 20(S),22(R), 23(S),24(R)-16beta:23;22:25-diepoxy-12beta-acetoxy-3be ta,23, 24-trihydroxy-9,19-cycloanost-7-ene-3-O-beta-D-xylopyranoside (6), 20(S),22(R),23(S),24(R)-16beta:23;22:25-diepoxy-12beta -acetoxy-3beta, 23,24-trihydroxy-9,19-cycloanost-7-en-3-O-alpha-L-arabinopyrano side (7), and 20(S),22(R),23(S), 24(R)-16beta:23;22:25-diepoxy-12beta-acetoxy-3beta,23, 24-trihydroxy-9,19-cycloanostane-3-O-beta-D-xylopyranoside (8).

Glycosides↗

Novel glycosides from noni (Morinda citrifolia).

Three new glycosides were isolated from the fruits of noni (Morinda citrifolia). Their structures were determined to be 6-O-(beta-D-glucopyranosyl)-1-O-octanoyl-beta-D-glucopyranose (1), 6-O-(beta-D-glucopyranosyl)-1-O-hexanoyl-beta-D-glucopyranose (2), and 3-methylbut-3-enyl 6-O-beta-D-glucopyranosyl-beta-D-glucopyranoside (3) using MS and NMR methods.

Chromatography, Gel↗

Polyoxygenated bipyridine, pyrrolylpyridine, and bipyrrole alkaloids from Speranskia tuberculata.

Five novel polyoxygenated alkaloids, speranculatines A-C (3-5), speranskilatine A (6), and speranberculatine A (7), have been isolated from Speranskia tuberculata. Compounds 3-5, 6, and 7, have bipyridine, pyrrolylpyridine, and bipyrrole skeletons, respectively. This is the first time that these three alkaloid structural types have been reported. The structures of 3-7 were elucidated by spectroscopic methods, including 2D NMR techniques and X-ray crystallographic analysis.

Alkaloids↗

Identification of paraldol-deoxyguanosine adducts in DNA reacted with crotonaldehyde.

Crotonaldehyde (1) is a mutagen and carcinogen, but its reactions with DNA have been only partially characterized. In a previous study, we found that substantial amounts of 2-(2-hydroxypropyl)-4-hydroxy-6-methyl-1,3-dioxane (paraldol, 7), the dimer of 3-hydroxybutanal (8), were released upon enzymatic or neutral thermal hydrolysis of DNA that had been allowed to react with crotonaldehyde. We have now characterized two paraldol-deoxyguanosine adducts in this DNA: N(2)-[2-(2-hydroxypropyl)-6-methyl-1,3-dioxan-4-yl]deoxyguanosine (N(2)-paraldol-dG, 13) and N(2)-[2-(2-hydroxypropyl)-6-methyl-1, 3-dioxan-4-yl]deoxyguanylyl-(5'-3')-thymidine [N(2)-paraldol-dG-(5'-3')-thymidine, 14]. Four diastereomers of N(2)-paraldol-dG (13) were observed. Their overall structures were determined by (1)H NMR, by MS, and by reaction of paraldol with deoxyguanosine and DNA. (1)H NMR data showed that two diastereomers had all equatorial substituents in the dioxane ring, while two others had an axial 6-methyl group. Preparation of paraldol with the (R)- or (S)-configuration at the 6-position of the dioxane ring and the carbinol carbon of the 2-(2-hydroxypropyl) group allowed partial assignment of the absolute configurations of N(2)-paraldol-dG (13). Four diastereomers of N(2)-paraldol-dG-(5'-3')-thymidine (14) were observed. Their overall structure was determined by (1)H NMR, MS, and hydrolysis with snake venom or spleen phosphodiesterase. Reactions of nucleosides and nucleotides with paraldol demonstrated that adducts were formed only from deoxyguanosine and its monophosphates. Experiments with DNA that had been reacted with crotonaldehyde indicated that N(2)-paraldol-dG-containing adducts in DNA are relatively resistant to enzymatic hydrolysis. The results of this study demonstrate that the reaction of crotonaldehyde with DNA is more complex than previously recognized and that stable N(2)-paraldol-dG adducts are among those that should be considered in assessing mechanisms of crotonaldehyde mutagenicity and carcinogenicity.

Aldehydes↗

Identification of DNA adducts of acetaldehyde.

Acetaldehyde is a mutagen and carcinogen which occurs widely in the human environment, sometimes in considerable amounts, but little is known about its reactions with DNA. In this study, we identified three new types of stable acetaldehyde DNA adducts, including an interstrand cross-link. These were formed in addition to the previously characterized N(2)-ethylidenedeoxyguanosine. Acetaldehyde was allowed to react with calf thymus DNA or deoxyguanosine. The DNA was isolated and hydrolyzed enzymatically; in some cases, the DNA was first treated with NaBH(3)CN. Reaction mixtures were analyzed by HPLC, and adducts were isolated and characterized by UV, (1)H NMR, and MS. The major adduct was N(2)-ethylidenedeoxyguanosine (1), which was identified as N(2)-ethyldeoxyguanosine (7) after treatment of the DNA with NaBH(3)CN. The new acetaldehyde adducts were 3-(2-deoxyribos-1-yl)-5,6,7, 8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one (9), 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-(N(2)-deoxyguanosyl+ ++)- 6-methylpyrimido[1,2-a]purine-10(3H)one (12), and N(2)-(2, 6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (11). Adduct 9 has been previously identified in reactions of crotonaldehyde with DNA. However, the distribution of diastereomers was different in the acetaldehyde and crotonaldehyde reactions, indicating that the formation of 9 from acetaldehyde does not proceed through crotonaldehyde. Adduct 12 is an interstrand cross-link. Although previous evidence indicates the formation of cross-links in DNA reacted with acetaldehyde, this is the first reported structural characterization of such an adduct. This adduct is also found in crotonaldehyde-deoxyguanosine reactions, but in a diastereomeric ratio different than that observed here. A common intermediate, N(2)-(4-oxobut-2-yl)deoxyguanosine (6), is proposed to be involved in formation of adducts 9 and 12. Adduct 11 is produced ultimately from 3-hydroxybutanal, the major aldol condensation product of acetaldehyde. Levels of adducts 9, 11, and 12 were less than 10% of those of N(2)-ethylidenedeoxyguanosine (1) in reactions of acetaldehyde with DNA. As nucleosides, adducts 9, 11, and 12 were stable, whereas N(2)-ethylidenedeoxyguanosine (1) had a half-life of 5 min. These new stable adducts of acetaldehyde may be involved in determination of its mutagenic and carcinogenic properties.

Acetaldehyde↗

Dynamic mechanical characterization of hydroxyapatite reinforced polyethylene: effect of particle size.

Dynamic mechanical analysis (DMA) was used to characterize biomedical composites consisting of synthetic hydroxyapatite (HA) particulate reinforced polyethylene (PE). The effects of the HA volume fraction, temperature and HA particle on the storage modulus (E(I)) and damping (tan delta) were investigated. Increasing HA volume fractions increased E(I) and decreased tan delta. E(I) was found to be linearly related to the Young's modulus values obtained from quasi-static tensile tests. Relative modulus and damping studies showed that the viscoelastic behavior of unfilled PE was different to that of the filled matrix due to the presence of thermally induced tensile stresses in the matrix at the filler-matrix interface.

Journal Article↗

Autosomal recessive juvenile parkinsonism: a key to understanding nigral degeneration in sporadic Parkinson's disease.

The contribution of genetic factors to the pathogenesis of Parkinson's disease (PD) is supported by the demonstration of the high concordance in twins studies using positron emission tomography (PET), the increased risk among relatives of PD patients in case-control and family studies, and the existence of familial PD and parkinsonism by single gene defect. Recently several genes have been mapped and/or identified. Alpha-synuclein is involved in a rare dominant form of familial PD with dopa-responsive parkinsonism features and Lewy body-positive pathology. In contrast, parkin is responsible for the autosomal recessive form (AR-JP) of early onset PD with Lewy body-negative pathology. The clinical features of this form include early onset (in the 20s), levodopa-responsive parkinsonism, diurnal fluctuation, and slow progression of the disease. Parkin consists of 12 exons and the estimated size is over 1.5 Mb. To date, variable mutations such as deletions or point mutations resulting in missense and nonsense changes have been reported in AR-JP patients. In addition, the localization of parkin indicates that parkin may be involved in the axonal transport system. More recently we have found that parkin interacts with the ubiquitin-conjugating enzyme E2 and is functionally linked to the Ub-proteasome pathway as a ubiquitin ligase, E3. These findings fit the characteristics of a lack of Lewy bodies (these are cytoplasmic inclusions that are considered to be a pathological hallmark). Our findings should enhance the exploration of the mechanisms of neuronal death in PD as well as other neurodegenerative disorders of which variable inclusion bodies are observed.

Chromosomes, Human, Pair 6↗

Deficit in conditional visuomotor learning by local infusion of bicuculline into the ventral prefrontal cortex in monkeys.

To explore the role of the ventral prefrontal cortex (PFv) in conditional visuomotor learning, we infused locally bicuculline, a GABAergic antagonist, into the PFv of two monkeys, well trained on a two-problem visuomotor task. The task required the monkeys to execute one of two motor actions (moving a handle to the left or to the right) in response to one of two familiar visual patterns (circle or triangle). The two patterns mapped 1:1 onto the two motor actions: for each pattern one and only one motor action was scored, correct and reinforced. In contrast to these sessions with familiar patterns, in the learning sessions the monkeys were presented with one or two novel patterns and required to learn the arbitrarily determined associations between these patterns and the two motor actions. We found that bilateral infusion of bicuculline into PFv dramatically impaired the monkeys' ability to learn novel pattern-response associations: the trials and errors to criterion (90% correct) increased significantly. The errors were mainly an inability to apply 'Win-Stay', 'Lose-Shift' and 'Change-Shift' strategies. There was no effect on the monkeys' performance in responding to familiar patterns. Similar infusion of bicuculline into the dorsal prefrontal cortex was without effect on either novel-pattern learning or familiar-pattern performance. We conclude that the ventral prefrontal cortex is necessary for learning new visuomotor associations, but has less importance, if any, for performing pre-established ones.

Animals↗

Fine mapping and characterization of candidate lung tumor resistance genes for the Par2 locus on mouse chromosome 18.

In a number of recent studies, a lung tumor resistance locus designated either Par2 or Pas7 was mapped to distal chromosome 18 in crosses between susceptible A/J and more resistant BALB/c mice. This locus is important in that it accounts for as much as 60% of the difference in lung tumor susceptibility between the A/J and BALB/c mice, both of which contain the susceptible allele of Kras2, a marker and strong candidate for the major lung tumor susceptibility gene on mouse chromosome 6. We have now fine-mapped the Par2 locus by using congenic mice that were constructed by placing part of chromosome 18 from the susceptible A/J onto the genetic background of lung tumor-resistant BALB/c mice. After 7 generations of backcrossing, N7 mice that carried 28 cM of the A/J quantitative trait locus (QTL) region were crossed to the BALB/c to generate the N8 generation. Congenic strains (N8) that contain various QTL regions were generated. N9 mice, generated from N8 males x 3 BALB/c females, were genotyped in the region of the Par2 locus and treated with an initiating dose of urethane and allowed to form lung tumors over 6 months. The mice were killed and the lung tumors counted. With this cross the Par2 locus was narrowed to a 6-cM region. Potential candidate genes in this region include Smad4, Smad2, and Dcc. Previously, we excluded Smad4 and Smad2 as candidates for Par2 based on the lack of functional polymorphism(s) and differential expression in lungs from A/J and BALB/c mice. In this study, no polymorphism of the coding sequence of Dcc was observed between A/J and BALB/c mice. Further fine mapping and positional cloning are required for the identification of the Par2 gene.

Adenoma↗

Cardiovascular responses to simulated microgravity in Sprague-Dawley rats.

Microgravity is known to induce orthostatic intolerance and baroreflex impairment in astronauts. Cardiovascular responses observed in 30 degrees head-down tilt rat models, whether 24 hr whole body suspension (WBS) or 7 day tail-suspension (TS), mimic observations made during exposure to microgravity. We evaluated the cardiovascular effects of simulated microgravity and the subsequent post-suspension in rats using the above models. Mean arterial pressure (MAP) of both WBS and TS rats did not change during suspension. In both models, MAP decreased post-suspension and this response lasted for 6 hrs. Salt-loaded animals did not show a post-suspension reduction in MAP. Plasma ionized calcium was decreased at 2 hr of WBS, with no change in sodium, potassium, magnesium, glucose, or hematocrit. Body weight changes were similar for all animals whether under suspension or control conditions. Both rat models demonstrate post-suspension hypotension and these results support the notion that salt-loading may have some beneficial effects in ameliorating this hypotension.

Animals↗

3D simulation of EIT for monitoring impedance variations within the human head.

A preliminary analysis is presented concerning the use of EIT for detecting impedance inhomogeneities within the human brain. The work to date is centred around the monitoring of two distinct impedance variations: those associated with the application of a carotid clamp during surgery and changes caused by the redistribution of blood flow during auditory stimuli. Using the commercially available Ansoft Maxwell package, a 3D finite element model of the human head has been developed to solve the forward problem. The model is hemispherical in shape and comprises regions of brain, cerebrospinal fluid, skull and skin and includes 16 scalp electrodes each of area 1 cm2. Results from simulations using the model suggest that an EIT system, incorporating diametric current excitation, would require a voltage measurement sensitivity of 100-120 dB in order to detect the impedance variations in the above cases.

Acoustic Stimulation↗

Effects of benzyl isothiocyanate and phenethyl isothiocyanate on benzo[a]pyrene metabolism and DNA adduct formation in the A/J mouse.

Benzyl isothiocyanate (BITC) inhibits lung tumorigenesis induced in A/J mice by benzo[a]pyrene (B[a]P). In contrast, phenethyl isothiocyanate (PEITC) does not. We tested the hypothesis that BITC inhibits B[a]P tumorigenicity in mouse lung by inhibiting DNA adduct formation, and compared the effects of BITC and PEITC. In mouse liver or lung microsomal incubations, BITC and PEITC inhibited formation of 7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (B[a]P-7, 8-diol) and some other B[a]P metabolites. The metabolism of B[a]P was compared in mouse lung and liver microsomes, 6 or 24h after treatment with BITC or PEITC. In lung, 6 h after treatment, B[a]P-7, 8-diol and some other metabolites were inhibited by BITC and PEITC. However, 24 h after treatment, no inhibition of B[a]P-7,8-diol was observed in microsomes from BITC-treated mice, whereas it was substantially increased in mice treated with PEITC. Effects on B[a]P metabolism in liver microsomes were generally modest. Conversion of B[a]P-7,8-diol to mutagens by mouse liver microsomes was more strongly inhibited by BITC than PEITC. Effects on 7,8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA adduct formation were evaluated in DNA from mice treated with isothiocyanates and B[a]P, and killed 2-120h later. The area under the curve (AUC) for BPDE-DNA adducts in lung was 29.5% less (P = 0. 001) in the BITC-B[a]P treated mice and 19.0% less (P = 0.02) in the PEITC-B[a]P mice than in the mice treated with B[a]P alone. Similar results were obtained in liver DNA. There were no significant differences between the reduction of BPDE-DNA AUC values by BITC versus PEITC. The results of this study support the hypothesis that BITC inhibits B[a]P-induced lung tumorigenesis in A/J mice by inhibiting the metabolic activation of B[a]P to BPDE-DNA adducts. However, differences in BPDE-DNA adduct formation do not appear to explain fully the contrasting effects of BITC and PEITC on B[a]P-induced lung tumorigenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗