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Biomedical subjects

M Wang

Publications and source records attributed to M Wang.

At least 775 records · Page 43Linked to original sources
PubMed1995

Formation of N2-tetrahydrofuranyl and N2-tetrahydropyranyl adducts in the reactions of alpha-acetoxy-N-nitrosopyrrolidine and alpha-acetoxy-N-nitrosopiperidine with DNA.

We studied the reactions with DNA of alpha-acetoxy-N-nitrosopyrrolidine (alpha-acetoxyNPYR) and alpha-acetoxy-N-nitrosopiperidine (alpha-acetoxyNPIP) in order to obtain more information on adduct formation by metabolic activation via alpha-hydroxylation of two cyclic nitrosamines, N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP). Enzyme hydrolysis and HPLC analysis of DNA that had been reacted with unlabeled, [14C]-, or [3H]alpha- acetoxyNPYR permitted the positive identification of N2-(tetrahydrofuran-2-yl)deoxyguanosine (THF-dG). It was identified by comparison of its UV spectrum and retention time to those of a standard, by conversion upon NaBH4 treatment to N2-(4-hydroxybutyl)deoxyguanosine, and by neutral thermal hydrolysis to 2-hydroxytetrahydrofuran (THF-OH). The levels of THF-dG in DNA exceeded that of other adducts of alpha-acetoxyNPYR. Reaction of alpha-acetoxyNPIP with DNA followed by enzyme hydrolysis and HPLC analysis resulted in the positive identification of two diastereomers of N2-(3,4,5,6-tetrahydro-2H-pyran-2-yl)deoxyguanosine (THP-dG) by comparison of their retention times and UV spectra to those of standards. The levels of THP-dG were similar to those of THF-dG formed from alpha-acetoxyNPYR. Neutral thermal hydrolysis of DNA that had been reacted with alpha-acetoxyNPIP produced 2-hydroxy-3,4,5,6-tetrahydro-2H-pyran (THP-OH). Studies on the mechanism of formation of THF-dG and THP-dG indicated that stable cyclic oxonium ion-derived electrophiles could be their major precursors. Our data provide the first evidence for the formation of cyclic oxonium ion-derived DNA adducts from cyclic nitrosamines and indicate some potential differences in DNA binding between alpha-acetoxyNPYR and alpha-acetoxyNPIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogens↗
PubMed1995

Foetal magnetocardiogram amplitude oscillations associated with respiratory sinus arrhythmia.

We show that oscillations at foetal breathing frequencies observed in foetal heart rate (FHR) tracings obtained from foetal magnetocardiogram (FMCG) recordings are often accompanied by synchronous modulation of FMCG signal amplitude. This implies an association between the FHR oscillations and foetal chest wall movements, corroborating the hypothesis that the oscillations are due to respiratory sinus arrhythmia.

Adult↗
PubMed1995

The grouped node technique as a means of handling large electrode surfaces in electrical impedance tomography.

A finite-element method employing a grouped node technique as a means of handling large electrode surfaces in electrical impedance process tomography is presented. The technique groups sets of nodes representing discrete boundary electrodes in a two-dimensional finite-element mesh into corresponding sets of single nodes via a transformation matrix G. The subsequent field solution is obtained based on the new boundary conditions in the standard way after implementing this procedure. Comparison of the resultant boundary voltage profiles from this approach against measurements made on laboratory scale phantoms are reported.

Algorithms↗
PubMed1995

Conducting boundary strategy: a new technique for medical EIT.

A medical application of a new measurement strategy developed for process tomography is presented. By exchanging the current streamlines with the equipotential lines impedance tomography can be performed using unipolar measurements. The equipotential lines are now parallel to the conducting boundary and voltage measurement is made between this boundary and an insulated electrode. A set of 32 electrodes was placed around the chest with every alternate electrode connected to form the 'conducting boundary'. A total of 120 independent measurements were available. Reciprocity error without common mode feedback was 0.5% with a dynamic range of only 1:1.12. The images were comparable to that reconstructed using adjacent drive strategy.

Electric Impedance↗
PubMed1995

Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta.

In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have examined the ethnic distribution of this polymorphism using a polymerase chain reaction (PCR)-based genotyping method. Five different ethnic groups were studied: North American Caucasians, African-Americans, Mexican-Americans, Chinese and Koreans. The prevalence of the null genotype was highest among Chinese (64.4%), followed by Koreans (60.2%), African-Americans (21.8%) and Caucasians (20.4%), whereas the prevalence was lowest among Mexican-Americans (9.7%). Interestingly, the prevalence of the deleted genotype in Caucasians differed significantly when 257 individuals drawn from a nation wide organization were compared with 185 people from the New England area (23.7 versus 15.7%, P < 0.05, chi 2 test). These results indicate that there are major differences in the prevalence of this trait attributable to ethnicity and that ethnic origin even among Caucasians should be considered in studies of gene-environment interaction involving this polymorphism.

Asian People↗
PubMed1995

Quantitative DNA fiber mapping.

The assembly of sequence ready, high-resolution physical maps and construction of minimally overlapping contigs for the human as well as model genomes requires accurate determination of the extent of overlap between adjacent clones as well as their relative orientation. This is presently done by procedures such as clone fingerprinting, Southern blot analysis or clone end sequencing. We present a complementary analytical technique to map directly cloned DNA sequences on to individual stretched DNA molecules. This approach uses the hydrodynamic force of a receding meniscus to prepare straight high molecular weight DNA molecules that provide a linear template of approximately 2.3 kb/microns on to which the cloned probes can be mapped by in situ hybridization. This technique has numerous advantages such as a very high density of mapping templates, reproducible stretching of the mapping template providing a linear genomic scale, determination of clone orientation and direct visualization of DNA repeats. The utility and accuracy of quantitative DNA fiber mapping are illustrated through three examples: (i) mapping of lambda DNA restriction fragments along linearized approximately 49 kb long lambda phage DNA molecules with approximately 1 kb precision; (ii) localization of the overlap between a cosmid and a colinear P1 clone; and (iii) mapping of P1 clones along an approximately 490 kb yeast artificial chromosome (YAC) with approximately 5 kb precision and estimation of the approximately 25 kb gap between them.

Bacteriophage lambda↗
PubMed1995

Recurrent mis-splicing of fibrillin exon 32 in two patients with neonatal Marfan syndrome.

The Marfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue. Variable and pleiotropic clinical features are observed in the skeletal, ocular, and cardiovascular systems. The most severe end of the phenotypic spectrum of this disorder comprises a group of patients usually diagnosed at birth, who have a life expectancy of little more than a year. To distinguish this group of patients from those with classical MFS, we refer to them as neonatal Marfan syndrome (nMFS). These infants usually die of congestive heart failure rather than aortic aneurysmal disease, the most frequent cause of morbidity and mortality in classical MFS. Defects in fibrillin, an elastin-associated microfibrillar glycoprotein, are now known to cause both the classical and neonatal forms of MFS. Here we report the recurrent mis-splicing of fibrillin (FBN1) exon 32, a precursor EGF-like calcium binding domain, in two unrelated infants with nMFS. The mis-splicing, in one patient, was due to an A-->T transversion at the -2 position of the consensus acceptor splice site; while that in the second patient was caused by a G-->A transition at the +1 position of the donor splice site. Characterization of FBN1 mutations in individuals at the most severe end of the Marfan syndrome spectrum should provide greater understanding of the multiple domains and regions of fibrillin.

Alleles↗
PubMed1995

Dietary nicotinamide supplementation increases xanthine oxidoreductase activity in the kidney and heart but not liver of obese Zucker rats.

The conversion of xanthine dehydrogenase to xanthine oxidase that produces oxygen radicals has been implicated in the ischemic injury to the myocardium and to the kidney. Xanthine dehydrogenase uses NAD as the electron acceptor to catalyze a reaction which does not produce any oxygen free radicals and may depress the conversion of xanthine dehydrogenase to xanthine oxidase. Nicotinamide is the preferred precursor for NAD. This study was conducted to examine the effect of an 18% casein diet supplemented with 0.5% nicotinamide on the activity of oxidoreductase and its two enzyme forms, xanthine dehydrogenase and xanthine oxidase, in kidney, heart and liver of female obese Zucker rats that spontaneously develop glomerulosclerosis, cardiomegaly and fatty liver. Lean litter mates were used as controls. Nicotinamide supplementation had no effect on the activities of these enzyme forms in the liver of either obese rats or lean rats. Obese rats fed the nicotinamide supplemented diet had higher activities of these enzyme forms in kidneys and hearts than unsupplemented diet fed obese rats, but this difference was not observed in lean rats. In unsupplemented rats, xanthine oxidase activity in the kidney was greater in lean rats than obese rats. Thus, the abnormalities observed in obese rats are unlikely attributable to the xanthine oxidase-mediated oxidant stress.

Animals↗
PubMed1995

Anti-tumor activity of cytotoxic T lymphocytes elicited with recombinant and synthetic forms of a model tumor-associated antigen.

The recent cloning of tumor-associated antigens (TAAs) recognized by CD8+ T lymphocytes (TCD8+) has made it possible to use recombinant and synthetic forms of TAAs to generate TCD8+ with anti-tumor activity. To explore new therapeutic strategies in a mouse model, we retrovirally transduced the experimental murine tumor CT26(H-2d), with the lacZ gene encoding our model TAA, beta-galactosidase (beta-gal). The transduced cell line, CT26.CL25, grew as rapidly and as lethally as the parental cell line in normal, immunocompetent animals. In an attempt to elicit TCD8+ directed against our model TAA by using purely recombinant and synthetic forms of our model TAA, we synthesized a nine-amino-acid long immunodominant peptide of beta-gal (TPH-PARIGL), corresponding to amino acid residues 876-884, which was known to be presented by the Ld major histocompatibility complex (MHC) class I molecule, and a recombinant vaccinia virus encoding the full-length beta-gal protein (VJS6). Splenocytes obtained from naïve mice and co-cultured with beta-gal peptide could not be expanded in primary ex vivo cultures. However, mice immunized with VJS6, but not with a control recombinant vaccinia virus, yielded splenocytes that were capable of specifically lysing CT26.CL25 in vitro after co-culture with beta-gal peptide. Most significantly, adoptive transfer of these cells could effectively treat mice bearing 3-day-old established pulmonary metastases. These observations show that therapeutic TCD8+ directed against a model TAA could be generated by using purely recombinant and synthetic forms of this antigen. These findings point the way to a potentially useful immunotherapeutic strategy, which has been made possible by the recent cloning of immunogenic TAAs that are expressed by human malignancies.

Amino Acid Sequence↗
PubMed1995

Seroepidemiological and molecular evidence for the presence of two H3N8 equine influenza viruses in China in 1993-94.

In May 1993, a severe epidemic of respiratory disease began in horses in Inner Mongolia and spread throughout horses in China. The disease affected mules and donkeys as well as horses but did not spread to other species, including humans. The severity of the disease raised the question of whether the outbreak might have been caused by the new avian-like influenza viruses detected in horses in China in 1989 or by current variants ofA/equine/Miami/1/63 (H3N8) (equine-2) or by a reassortant between these viruses. Antigenic and sequence analysis established that all gene segments of the influenza virus causing the epidemic were of recent equine-2 origin and that the virus was not a reassortant. Serological analysis of post-infection horse sera provided evidence for the continued circulation of the A/Equine/Jilin/1/89 (Eq/Jilin) (H3N8) avian-like viruses in horses in Heilongjiang province with original antigenic sin-like responses. It is noteworthy that prior infection with the avian-like Eq/Jilin strain did not afford cross-protection against a current equine-2 strain. Serological evidence for the continued circulation of the avian-like H3N8 influenza virus in horses indicates that this virus has probably established itself in horses in Asia.

Animals↗
PubMed1995

Spectral patterns and frequency response characteristics of arterial pressure in heart paced dogs.

The role of heart rate in buffering and/or generating aortic pressure (AP) oscillations that occur at rest and in response to oscillatory blood volume shifts was studied. Six supine dogs with chronic AV blockade were used to examine: 1) resting HR and AP spectra when the ventricular rate was controlled by atrial depolarization (natural sinus rhythm); 2) resting AP and stroke volume (SV) spectra when the heart was AV sequentially paced at 60, 120, and 180 bpm before and after ganglionic blockade; and 3) the frequency response characteristics of AP and SV to whole-body sinusoidal acceleration (+/- 2gz, 0.008-0.23 Hz) at each heart rate before and after ganglionic blockade. During atrial regulation of HR, the spectra of both AP and HR had dominant peaks located at the breathing frequency (0.2-0.4 Hz) and relatively smaller peaks centered at approximately 0.05 Hz. During constant heart rate pacing, the spectra of AP had a dominant component at approximately 0.05 Hz. The power of this component was: 1) larger than during atrial regulation, 2) increased with increasing pacing rate, and 3) abolished by ganglionic blockade. There was no effect of pacing rate or ganglionic blockade on SV spectra. During oscillatory acceleration, AP regulation in the heart paced dogs was frequency dependent. Regions of good regulation occurred below 0.016 Hz and above 0.1 Hz, and poor regulation between 0.035 and 0.075 Hz centered at approximately 0.05 Hz. The oscillations in the poor regulation region were enhanced by increased pacing rate. After ganglionic blockade, the frequency response of AP was primarily hydraulic (low-pass). The frequency response of SV had a neural component. We conclude that: 1) resting AP fluctuations at respiratory frequencies resulted from respiration-linked HR variation; 2) the 0.05-Hz fluctuations in AP during rest and the poor regulation of AP at 0.05 Hz during acceleration resulted from a peripheral vascular response that lagged disturbances by approximately 10 s; 3) HR regulation was important in minimizing AP variation in the 0.05-Hz region both at rest and during oscillatory acceleration; and 4) inotropic control of SV was an important component of AP regulation during low-frequency acceleration.

Acceleration↗
PubMed1995

Initial studies of the structural signal for extracellular transport of cholera toxin and other proteins recognized by Vibrio cholerae.

The specificity of the pathway used by Vibrio cholerae for extracellular transport of cholera toxin (CT) and other proteins was examined in several different ways. First, V. cholerae was tested for the ability to secrete the B polypeptides of the type II heat-labile enterotoxins of Escherichia coli. Genes encoding the B polypeptide of LT-IIb in pBluescriptKS- phagemids were introduced into V. cholerae by electroporation. Culture supernatants and periplasmic extracts were collected from cultures of the V. cholerae transformants, and the enterotoxin B subunits were measured by an enzyme-linked immunosorbent assay. Results confirmed that the B polypeptides of both LT-IIa and LT-IIb were secreted by V. cholerae with efficiencies comparable to that measured for secretion of CT. Second, the plasmid clones were introduced into strain M14, an epsE mutant of V. cholerae. M14 failed to transport the B polypeptides of LT-IIa and LT-IIb to the extracellular medium, demonstrating that secretion of type II enterotoxins by V. cholerae proceeds by the same pathway used for extracellular transport of CT. These data suggest that an extracellular transport signal recognized by the secretory machinery of V. cholerae is present in LT-IIa and LT-IIb. Furthermore, since the B polypeptide of CT has little, if any, primary amino acid sequence homology with the B polypeptide of LT-IIa or LT-IIb, the transport signal is likely to be a conformation-dependent motif. Third, a mutant of the B subunit of CT (CT-B) with lysine substituted for glutamate at amino acid position 11 was shown to be secreted poorly by V. cholerae, although it exhibited immunoreactivity and ganglioside GM1-binding activity comparable to that of wild-type CT-B. These findings suggest that Glu-11 may be within or near the extracellular transport motif of CT-B. Finally, the genetic lesion in the epsE allele of V. cholerae M14 was determined by nucleotide sequence analysis.

Alleles↗
PubMed1995

Infection by retroviral vectors outside of their host range in the presence of replication-defective adenovirus.

Retrovirus infection is normally limited to cells within a specific host range which express a cognate receptor that is recognized by the product of the env gene. We describe retrovirus infection of cells outside of their normal host range when the infection is performed in the presence of a replication-defective adenovirus (dl312). In the presence of adenovirus, several different ecotropic vectors are shown to infect human cell lines (HeLa and PLC/PRF), and a xenotropic vector is shown to infect murine cells (NIH 3T3). Infectivity is demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining, selection with G418 for neomycin resistance, and PCR identification of the provirus in infected cells. Infectivity is quantitatively dependent upon both the concentration of adenovirus (10(6) to 10(8) PFU/ml) and the concentration of retrovirus. Infection requires the simultaneous presence of adenovirus in the retrovirus infection medium and is not stimulated by preincubation and removal of adenovirus from the cells before retrovirus infection. The presence of adenovirus is shown to enhance the uptake of fluorescently labeled retrovirus particles into cells outside of their normal host range, demonstrating that the adenovirus enhances viral entry into cells in the absence of the recognized cognate receptor. This observation suggests new opportunities for developing safe retroviral vectors for gene therapy and new mechanisms for the pathogenesis of retroviral disease.

3T3 Cells↗
PubMed1995

Effects of moderate dose alcohol on visual contrast sensitivity for stationary and moving targets.

OBJECTIVE: Contrast sensitivity involves distinguishing threshold luminance differences and is usually assessed using static sine-wave gratings over a range of different spatial frequencies. The purpose of this study was to determine the effects of various levels of acute alcohol intoxication on contrast sensitivity to stationary and moving sine-wave gratings. Moving gratings required the subjects to make pursuit eye movements. A secondary goal was to investigate whether any alcohol-related effects were associated with any measures of intoxication. METHOD: Male volunteers (N = 8) participated in three counterbalanced, double-blind, testing sessions (low alcohol, moderate alcohol and placebo) plus a control session with no beverage. Breath alcohol concentration and two subjective measures of intoxication were measured for each subject. Static and dynamic contrast sensitivity were determined for electronically generated sine-wave gratings that were either stationary or traveled in a circular path with a diameter of 9 cm (3.7 degrees) at 51.7 rpm, thus requiring the subject to make smooth pursuit eye movements. RESULTS: The mean blood alcohol concentration measured in the moderate alcohol condition was 0.043% and in the low alcohol condition 0.011%. Moderate dose alcohol consumption significantly impaired both static and dynamic contrast with a greater effect for moving targets. CONCLUSIONS: Objective and subjective measures of intoxication were unrelated to the alcohol-related losses in contrast sensitivity. Although most states currently prohibit driving with BACs of 0.08-0.10%, the present data indicate reliable visual impairment at approximately half of that level (.44%).

Adult↗
PubMed1995

Dyspnea and exercise testing in workers exposed to silica.

In order to provide a better objective assessment of exertional dyspnea and functional impairment due to exposure to silica, 153 workers exposed to silica dust (workers) and 62 patients with silicosis (patients) were performed the medical questionnaires with special reference to exertional dyspnea and exercise testing on bicycle ergometer. Complaints of breathlessness were present in 77 (50%) workers and 53 (85%) patients. The findings of exercise tests indicated that there were definite correlations between index of dyspnea (ID), or breathing reserve (BR) and complaint of breathlessness in both the workers and patients. ID increased and BR decreased with the increasing degree of breathlessness. We defined ID > 70% or BR < 25 I/min as abnormal criteria and checked the ratios of dyspnea quantified objectively. Thus, 30% of the workers and 56% of the patients in this study were verified to have slight or moderate breathlessness, which were considerably lower than that derived from questionnaire on dyspnea. OUr results suggest that objective physiological measures like exercise testing may be of value in evaluating dyspnea in workers exposed to silica.

Adult↗
PubMed1995

Effects of smoking on respiratory function and exercise performance in asbestos workers.

To determine the role of smoking in the development of pulmonary impairment in asbestos workers, 66 nonsmoking asbestos workers and 70 smoking asbestos workers were studied. Occupational and medical questionnaires, lung function and exercise test were conducted in all subjects. The frequencies of dyspnea and cough on questions were significantly higher in the smoking workers than those in nonsmoking workers. Similarly, FEV1, FEV1/FVC and DLco were significantly lower in the smoking workers. Exercise performance showed that the smoking workers had higher index of dyspnea and lower breathing reserve, Vo2 and Vo2 max than nonsmoking workers did. We concluded that cigarette smoking has marked effects on both of respiratory function and exercise performance in asbestos workers. Among them, smokers show more serious obstructive impairment in static lung function testing and more significant limitation during exercise. The history of cigarette smoking deserves close attention in the evaluation of pulmonary impairment from asbestos exposure.

Asbestos↗