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Y S Cheng

Publications and source records attributed to Y S Cheng.

At least 55 records · Page 3Linked to original sources
PubMed1997

Measurements of airway dimensions and calculation of mass transfer characteristics of the human oral passage.

This paper presents measurements of the geometric shape, perimeter, and cross-sectional area of the human oral passage (from oral entrance to midtrachea) and relates them through dimensionless parameters to the depositional mass transfer of ultrafine particles. Studies were performed in two identical replicate oral passage models, one of which was cut orthogonal to the airflow direction into 3 mm elements for measurement, the other used intact for experimental measurements of ultrafine aerosol deposition. Dimensional data were combined with deposition measurements in two sections of the oral passage (the horizontal oral cavity and the vertical laryngeal-tracheal airway) to calculate the dimensionless mass transfer Sherwood number (Sh). Mass transfer theory suggests that Sh should be expressible as a function of the Reynolds number (Re) and the Schmidt number (Sc). For inhalation and exhalation through the oral cavity (O-C), an empirical relationship was obtained for flow rates from 7.5-30.0 1 min-1: Sh = 15.3 Re0.812 Sc-0.986 An empirical relationship was likewise obtained for the laryngeal-tracheal (L-T) region over the same range of flow rates: Sh = 25.9 Re0.861 Sc-1.37 These relationships were compared to heat transfer in the human upper airways through the well-known analogy between heat and mass transfer. The Reynolds number dependence for both the O-C and L-T relationships was in good agreement with that for heat transfer. The mass transfer coefficients were compared to extrathoracic uptake of gases and vapors and showed similar flow rate dependence. For gases and vapors that conform to the zero concentration boundary condition, the empirical relationships are applicable when diffusion coefficients are taken into consideration.

Absorption↗
PubMed1996

Cataractogenesis in transgenic mice containing the HIV-1 protease linked to the lens alpha A-crystallin promoter.

Several lines of transgenic mice were generated with either active or inactive forms of the human immunodeficiency virus type 1 (HIV-1) protease gene under the control of the mouse lens alpha A-crystallin promoter. Mice bearing the inactive protease coding sequence displayed no gross abnormalities in the lens, while mice with the active protease developed time-dependent bilateral cataracts. One line, TG61, developed cataracts in utero while the second line, TG72, developed cataracts postnatally. TG61 mice, homozygous for the transgene, developed severe microphthalmia and were significantly smaller than the control mice at postnatal day 30. two-dimensional-polyacrylamide gel electrophoresis analysis of the protein profiles of TG72 and TG61 lenses revealed extensive modifications in the lens crystallins. Proteolysis in the homozygous TG72 mouse lenses began at postnatal day 20 with the disappearance or partial loss of beta B1-, beta B3-, and beta A3-crystallins and the appearance of crystallin fragments. Protein leakage and the gradual breakdown of cytoskeletal elements also occurred. In contrast, the opacification of the homozygous TG61 lenses appeared to have been influenced by differentiation and developmental processes. It appears that HIV-1 protease expression activates other proteases, and these enzymes, in concert with HIV-1 protease, are responsible for the protein modifications that eventually result in the opacification of the lens.

Amino Acid Sequence↗
PubMed1996

Properties of gypsum with the addition of gum arabic and calcium hydroxide.

The purpose of this work was to study the effects of adding a mixture of gum arabic and calcium hydroxide to a type III stone and an improved die stone. The effect on the water/powder ratio, compressive and tensile strength, hardness, and setting expansion was determined. Data for mechanical properties were subjected to two-way analysis of variance, followed by the Bonferroni-Dunn procedure to determine any significance (1%) between pairs of means. For the type III material the additives had little effect on setting expansion, but the additives significantly improved surface hardness. The additives did not improve compressive or tensile strength for the type III materials. In contrast, the improved die stone's hardness was not enhanced by the additives, and in some instances a reduction in strength was observed. It was concluded that dental cast materials with superior surface properties can be produced by a simple change of formulation.

Analysis of Variance↗
PubMed1996

Activity of linked HIV-1 proteinase dimers containing mutations in the active site region.

Mutations were introduced into the active site triplet (Asp-Thr-Gly) of one or both subunits of a linked dimer of human immunodeficiency virus type 1 proteinase. Mutation of Thr to Ser in one or both subunits did not alter the activity of the enzyme substantially, whereas its mutation to Asn in one subunit caused a dramatic decrease in catalytic efficiency. Mutation of Gly to Val in one subunit also yielded an enzyme with very low activity. The enzymes containing Thr-->Asn and Gly-->Val mutations in both subunits resulted in inactive enzymes, based on their inability to self-process and on assay with an oligopeptide substrate. The dramatic decrease in enzyme efficiency of the mutants was interpreted using molecular models of the enzymes.

Aspartic Acid↗
PubMed1996

Genetic polymorphism of 4'-hydroxylation of S-mephenytoin in 148 Chinese of Han nationality.

AIM: To study genetic polymorphism of S-mephenytoin (S-Mep) 4'-hydroxylation in the Chinese population of Han nationality. METHODS: The lg metabolic ratio (MR) and lg hydroxylation index (HI) in the urine (0-12 h) after oral administration with 100 mg of racemic Mep tablet were determined by HPLC method in 148 consangeously unrelated native Chinese subjects and 21 individuals of 5 families. RESULTS: The lg MR and lg HI showed a bimodal distribution with an antimode of -1.00 and 1.50, respectively. The occurrence of poor metabolizers (PM) was 13.5% in the population. The pedigree analysis in 5 families indicated that deficient S-Mep hydroxylation was an autosomal recessive trait. CONCLUSIONS: The occurrence of PM for S-Mep 4-hydroxylation in Chinese was higher than that of the Caucasians, and both genetic modes were of autosomal recessive trait.

Adult↗
PubMed1995

Pulmonary toxicity of nickel subsulfide in F344/N rats exposed for 1-22 days.

Repeated inhalation of nickel subsulfide (Ni3S2) by F344/N rats for 3 months results in chronic active inflammation in the lung and atrophy of the olfactory epithelium. The primary purpose of this study was to determine early responses of the respiratory tract to inhaled Ni3S2 in rats and to track the course of development of such lesions in rats exposed for up to 22 days. A secondary purpose was to obtain an improved estimate of the half-time for clearance of Ni from Ni3S2-exposed lungs. Groups of F344/N rats were exposed to 0, 0.6 or 2.5 mg Ni3S2/m3, 6 h/day for 1-22 days. Histopathological changes in nose and lung, as well as biochemical and cytological changes in lung, as measured in bronchoalveolar lavage fluid (BALF) and lung tissue, alveolar macrophage (AM) viability and Ni concentration in lung were evaluated. Inflammatory lung lesions in rats exposed to 2.5 mg Ni3S2/m3 peaked in intensity after 4 days of exposure. Minimal degeneration of the olfactory epithelium was noted in the 2.5 mg Ni3S2/m3-exposed rats after day 4 of exposure, with atrophy of the olfactory epithelium occurring in rats killed at 22 days. Lactate dehydrogenase, beta-glucuronidase and total protein in BALF were significantly elevated within 7 days of exposure while alkaline phosphatase activity was significantly depressed. AM viability was significantly reduced after 2 days of exposure. Concentrations of Ni in lung increased rapidly during the first 7 days of exposure, but more slowly thereafter. Lung burden data from this and a previous study suggest a clearance half-time for Ni of 3.5-8 days. Results indicate that Ni3S2 is relatively soluble in lung and inhalation of concentrations near the current Threshold Limit Value of 1 mg Ni/m3 can produce detrimental changes in the respiratory tract of rats after only a few days of exposure.

Administration, Inhalation↗
PubMed1995

Mapping of network-forming, heparin-binding, and alpha 1 beta 1 integrin-recognition sites within the alpha-chain short arm of laminin-1.

Cell-interactive and architecture-forming functions are associated with the short arms of basement membrane laminin-1. To map and characterize these functions, we expressed recombinant mouse laminin-1 alpha-chain extending from the N terminus through one third of domain IIIb. This dumbbell-shaped glycoprotein (r alpha 1(VI-IVb)'), secreted by mammalian cells, was found to possess three activities. 1) Laminin polymerization was quantitatively inhibited by recombinant protein, supporting an alpha-chain role for a three-short arm interaction model of laminin self-assembly. 2) r alpha 1(VI-IVb)' bound to heparin, and the activity was localized to a subfragment corresponding to domain VI by 125I-heparin blotting. 3) PC12 rat pheochromocytoma cells adhered to, and rapidly extended branching neurites on, r alpha 1(VI-IVb)', with adhesion inhibited by alpha 1 and beta 1 integrin chain-specific antibodies. The ability of anti-laminin antibody to block PC12 cell adhesion to laminin was selectively prevented by absorption with r alpha 1(VI-IVb)' or alpha-chain domain VI fragment. This active integrin-recognition site could furthermore be distinguished from a second cryptic alpha 1 beta 1-binding site exposed by heat treatment of fragment P1', a short arm fragment lacking globules. Thus, a polymer-forming, a heparin-binding, and the active alpha 1 beta 1 integrin-recognition site are all clustered at the end of the alpha-chain short arm, the latter two resident solely in domain VI.

Amino Acid Sequence↗
PubMed1995

Particle clearance and histopathology in lungs of F344/N rats and B6C3F1 mice inhaling nickel oxide or nickel sulfate.

The goals of this study were to (1) determine the effects of repeated inhalation of relatively insoluble nickel oxide (NiO) and highly soluble nickel sulfate hexahydrate (NiSO4.6H2O) on lung particle clearance, (2) investigate the effects of repeated inhalation of NiO or NiSO4 on the pulmonary clearance of subsequently inhaled 85Sr-labeled microspheres, (3) correlate the observed effects on clearance with accumulated Ni lung burden and associated pathological changes in the lung, and (4) compare responses in F344 rats and B6C3F1 mice. Male F344/N rats and B6C3F1 mice were exposed whole-body to either NiO or NiSO4.6H2O 6 hr/day, 5 days/week for up to 6 months. NiO exposure concentrations were 0, 0.62, and 2.5 mg NiO/m3 for rats and 0, 1.25, and 5.0 mg NiO/m3 for mice. NiSO4.6H2O exposure concentrations were 0, 0.12, and 0.5 mg NiSO4.6H2O/m3 for rats and 0, 0.25, and 1.0 mg NiSO4.6H2O/m3 for mice. After 2 and 6 months of whole-body exposure, groups of rats and mice were acutely exposed nose-only to 63NiO (NiO-exposed animals only), 63NiSO4.6H2O (NiSO4.6H2O-exposed animals only), or to 85Sr-labeled polystyrene latex (PSL) microspheres (both NiO- and NiSO4.6H2O-exposed animals) to evaluate lung clearance. In addition, groups of rats and mice were euthanized after 2 and 6 months of exposure and at 2 and 4 months after the whole-body exposures were completed to evaluate histopathological changes in the left lung and to quantitate Ni in the right lung. Repeated inhalation of NiO results in accumulation of Ni in lungs of both rats and mice, but to a greater extent in lungs of rats. During the 4 months after the end of the whole-body exposures, some clearance of the accumulated Ni burden occurred from the lungs of rats and mice exposed to the lower, but not the higher NiO exposure concentrations. Clearance of acutely inhaled 63NiO was also impaired in both rats and mice, with the extent of impairment related to both exposure concentration and duration. However, the clearance of acutely inhaled 85Sr PSL microspheres was not impaired. The repeated inhalation of NiO resulted in alveolar macrophage (AM) hyperplasia with accumulation of NiO particles in both rats and mice, chronic alveolitis in rats, and interstitial pneumonia in mice. These lesions persisted throughout the 4-month recovery period after the NiO whole-body exposures were terminated. In contrast, repeated inhalation of NiSO4.6H2O did not result in accumulation of Ni in lungs of either rats or mice and did not affect the clearance of 63NiSO4.6H2O inhaled after either 2 or 6 months of NiSO4.6H2O exposure. Clearance of the 85Sr-labeled microspheres was significantly impaired only in rats exposed to the microspheres after 2 months of exposure to NiSO4.6H2O. Histopathological changes in rats were qualitatively similar to those seen in NiO-exposed rats. Only minimal histopathological changes were observed in NiSO4.6H2O-exposed mice. These results suggest that repeated inhalation of NiO at levels resulting in AM hyperplasia and alveolitis may impair clearance of subsequently inhaled NiO. The potential effects of repeated inhalation of soluble NiSO4.6H2O on the clearance of subsequently inhaled poorly soluble particles are less clear.

Administration, Inhalation↗
PubMed1995

Silicon carbide whiskers: characterization and aerodynamic behaviors.

Silicon carbide (SiC) whiskers are fiberlike materials with a wide range of industrial applications. Industrial hygiene samplings of the material are taken to monitor and control possible exposures to workers. This study characterizes an SiC whisker in detail, including its width-length distribution, aspect ratio, particle density, and aerodynamic size distribution. The SiC whiskers were aerosolized, and samples from a filter, cascade impactor, and aerosol centrifuge were taken. The diameter-length distribution of SiC fibers determined by electron microscopy from filter samples was found to follow the bivariate lognormal distribution. The aerodynamic size of a fiber aerosol depends not only on the particle dimension and density but also on the orientation of its axis with respect to flow. The results show that the aerodynamic size distribution obtained from the impactor was consistent with the predicted value, assuming the long axis of the fiber was parallel to the flow toward the collection substrate. On the other hand, the aerodynamic size in the aerosol centrifuge was consistent with results for a perpendicular orientation. A larger aerodynamic size (20-25%) was obtained in the case of impactor data as compared with centrifuge data. The respirable fraction estimated from the cascade impactor data was 65%, consistent with the estimate from bivariate analysis (67%) but smaller than the estimated fraction from the aerosol centrifuge (76%). The results show that the data obtained with the bivariate analysis of fiber dimensions had good correlation with the cascade impactor data, and this approach can be used to predict the aerodynamic size distribution and the size-selective fractions for fiber aerosols from filter samples.

Carbon↗
PubMed1994

Crystal structure of a tethered dimer of HIV-1 proteinase complexed with an inhibitor.

HIV-1 proteinase (HIV PR) is a dimeric enzyme composed of two identical polypeptide chains that associate with twofold symmetry. We have determined to 1.8 A the crystal structure of a covalently tethered dimer of HIV PR. The tethered dimer:inhibitor complex is identical in nearly every respect to the complex of the same inhibitor with the wild type dimeric molecule, except for the linker region. Our results suggest that the tethered dimer may be a useful surrogate enzyme for studying the effects of single site mutations on substrate and inhibitor binding as well as on enzyme asymmetry, and for simulating independent mutational drift of the two domains which has been proposed to have led to the evolution of modern day, single-chain aspartic proteinases.

Alcohols↗
PubMed1994

Intercomparison of activity size distributions of thoron progeny by alpha- and gamma-counting methods.

It is difficult to calibrate sampling devices using radon or thoron progeny or particles measuring 1-4 nm; therefore, an interlaboratory comparison is important to verify the performance of graded diffusion batteries for the activity size distributions of the "unattached" progeny. This paper describes the results of an interlaboratory comparison of 220Rn progeny size distributions using graded diffusion batteries by alpha- and gamma-counting methods with different data inversion schemes. Graded diffusion batteries designed at the Inhalation Toxicology Research Institute and at the Environmental Measurement Laboratory were used in the study. Screens and backup filters from the Environmental Measurement Laboratory-graded diffusion batteries were counted simultaneously in alpha counters for total alpha activities, and those of the Inhalation Toxicology Research Institute-graded diffusion batteries were counted in a gamma detector for gamma activities from 212Pb. Because of the different counting methods and data analysis procedures used, this interlaboratory study of 220Rn progeny allows a more rigorous way of testing instrument performance. 212Pb particles generated in well-controlled environments of oxygen, nitrogen, or oxygen with 1 ppm of nitrogen oxide were measured. In general, good agreement in activity size distributions was obtained from these two methods. Some differences observed in individual size spectra were attributable to the data inversion programs used in each laboratory. When the data were analyzed by the same computer program, most differences disappeared.

Alpha Particles↗
PubMed1994

Neutralization of thoron progeny in gases.

This paper reports charge neutralization phenomena of 212Pb particles in nitrogen or oxygen atmospheres with trace amounts of other gases. Newly produced thoron or radon progeny are positively charged, stable molecular clusters that are subsequently neutralized by several mechanisms. The charged clusters have a smaller diffusion coefficient than neutral clusters of the same size due to the interaction of the charge with the surrounding gas molecules. In this study, we have found that the diffusion coefficients of 212Pb in O2, N2, NH3/O2, NH3/N2, and C6H12/N2 (IPs between 15.58 and 9.8 eV) ranged between 0.015 and 0.030 cm2 s-1. In the case of C6H12/O2, NO2/O2, NO/O2, and dimethylamine/O2 (ionization potential between 9.8 and 8.23 eV), the diffusion coefficients have increased to between 0.046 and 0.69 cm2 s-1. These results are consistent with previous results of 218Po, indicating that charged progeny are neutralized by electron transfer from a gas molecule with a lower ionization potential than lead oxide. We estimate the ionization potential of lead oxide to range between 9.8 and 10.2 eV. 212Pb was also neutralized by an electron scavenging mechanism in NO2/nitrogen.

Air Pollution, Radioactive↗
PubMed1994

Pulmonary toxicity of inhaled diesel exhaust and carbon black in chronically exposed rats. Part I: Neoplastic and nonneoplastic lung lesions.

This study compared the pulmonary carcinogenicities and selected noncancer effects produced by chronic exposure of rats at high rates to diesel exhaust and carbon black. The comparison was intended to provide insight into the likely importance of the mutagenic organic compounds associated with the soot portion of diesel exhaust in inducing pulmonary carcinogenicity in diesel exhaust-exposed rats. The role of the organic fraction has become important in judging the usefulness of the substantial data base on carcinogenicity in rats for predicting lung cancer risk for humans, and for determining the most appropriate method of extrapolating results across species and exposure concentrations. Rats were exposed chronically to either diesel exhaust or carbon black, which served as a surrogate for diesel exhaust soot with much reduced mutagenic activity associated with its organic fraction. The sequestration of particles in the lung and the induction of pulmonary neoplasia and non-neoplastic changes in the lung were compared in detail. Samples also were provided to collaborators to examine adduct formation in lung DNA and hemoglobin. Approximately 140 female and 140 male F344/N rats were exposed for 16 hours per day, 5 days per week for up to 24 months, beginning at eight weeks of age, to diesel exhaust or carbon black at 2.5 mg or at 6.5 mg particles/m3 of air, or to clean air as controls. The diesel exhaust was generated by light-duty engines burning certification fuel and operating on an urban-duty cycle. The carbon black was selected because it had particle size and surface area characteristics similar to those of diesel exhaust soot, but markedly less mutagenic activity associated with its organic fraction when analyzed using procedures typically used in studies of diesel soot. Rats were killed after 3, 6, 12, 18, or 23 months of exposure to measure lung and lung-associated lymph node burdens of particles, lung weight, bronchoalveolar lavage indicators of inflammation, DNA adducts in whole lung and alveolar type II cells, and chromosome injury in circulating lymphocytes, and to perform histopathologic assessment. In addition, after 3 and 18 months of chronic exposure, one group of rats was acutely exposed to radiolabeled carbon black particles or to fluorescent microspheres. These exposures were conducted to examine the clearance of radiolabeled particles and the sequestration of the fluorescent microspheres in the lungs. These experiments provided information on clearance overload and particle dosimetry. The growth characteristics of lung neoplasms also were examined by transplanting neoplastic cells into athymic mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants, Occupational↗
PubMed1994

[Determination of mephenytoin and 4'-hydroxymephenytoin in urine by high performance liquid chromatography].

A simple, sensitive and reproducible HPLC assay is described for the determination of mephenytoin and 4'-hydroxymephenytoin in human urine. Phenobarbital was used as an internal standard. The compounds were separated on a mu-Bondapack RP-C18 column using a mobile phase of acetonitrile-distilled water (40:60, v/v). The temperature of the column was maintained at 50 degrees C, and the UV detector was set at 210 nm. Calibration curves in the range 0.05-1.00 micrograms/ml for mephenytoin and 0.5-100.0 micrograms/ml for 4'-hydroxymephenytoin were linear (r = 0.9998 and r = 0.9992, respectively). The average recovery was 95.10 +/- 2.95%, and the relative standard deviation within day and day to day was less than 10%. The detection limit for mephenytoin was 25 ng/ml and 4'-hydroxymephenytoin was 50 ng/ml. The method was used to study the metabolism of S-mephenytoin 4'-hydroxylatoin in 10 healthy volunteers. The 12 h urinary metabolic ratio (MR) and hydroxylation index (HI) were calculated to express interindividual variation in metabolism. Two of them exhibited defective 4'-hydroxylation of S-mephenytoin as poor metabolizers (HI: 1349.18 and 409.57; MR: 105.29 and 8.52). In the remaining 8 subjects, the HI ranged from 1.68 to 6.71 and the MR ranged from 0.002 to 0.015, as extensive metabolizers of S-mephenytoin.

Chromatography, High Pressure Liquid↗
PubMed1993

In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease.

Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.

Amino Acid Sequence↗
PubMed1993

Self-assembly and calcium-binding sites in laminin. A three-arm interaction model.

Laminin, a four-arm glycoprotein, polymerizes in vitro into networks similar to those found in basement membranes. We have dissected this calcium-dependent assembly by analyzing proteolytic fragment binding using equilibrium gel filtration, ultracentrifugation, and electron microscopy. The cathepsin G fragment C1-4 (three short arms) was found to aggregate with a critical concentration similar to that for laminin. Like laminin polymerization, this assembly was inhibited by the smaller elastase short arm fragments E4 (B1 domains VI and V) and E1' (A-B2 short arm complex). Fragment E4 bound directly to E1' in a calcium-dependent manner (KD = 1.4 microM). In contrast, homologous self-interactions of short arm fragments and all interactions of long arm fragments were considerably weaker or nonexistent. While electron micrographs of E1' or E4 alone contained mostly monomers, those of E1'/E4 mixtures contained dimers and oligomers with E1' dimers connected to each other through their A and B2 arms, often with visible E4 molecules at their junctions. 45Ca2+ bound principally to fragment E1' with localization to the end of the B2 chain. These data support a model in which polymerization requires the interaction of all three ligands, one from each short arm, with calcium activating assembly by binding to the B2 short arm.

Amino Acid Sequence↗