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S Chen

Publications and source records attributed to S Chen.

At least 1,513 records · Page 84Linked to original sources

Pharmacokinetics of ceftriaxone in humans.

Pharmacokinetics of the investigational cephalosporin ceftriaxone were studied after 30-min intravenous infusions of three ascending single doses of 0.5, 1, and 2 g crossed over in 12 normal subjects. Serially collected plasma and urine samples were analyzed for ceftriaxone by high-performance liquid chromatography. Plasma concentration-time profiles were characterized by a linear two-compartment open model with the following respective mean (+/- standard deviation) parameters at 0.5-, 1-, and 2-g dose levels: elimination half-life, 6.5 +/- 0.7, 6.2 +/- 0.8, and 5.9 +/- 0.7 h; apparent volume of distribution, 8.5 +/- 1.1, 9.0 +/- 1.1, and 10.1 +/- 1.0 liters; and plasma clearance, 929 +/- 150, 1,007 +/- 130, and 1,190 +/- 150 ml/h. The respective renal excretion parameters were as follows: renal clearance, 373 +/- 60, 399 +/- 50, and 533 +/- 128 ml/h; and percentage of dose excreted unchanged in the 48-h urine samples, 41 +/- 8, 39 +/- 5, and 43 +/- 10. The 6-h elimination half-life of ceftriaxone was 2- to 10-fold longer than those reported for marketed and other known investigational cephalosporins. The small dose-related increases in the apparent volume of distribution and clearance parameters can be explainhe 48-h urine samples, 41 +/- 8, 39 +/- 5, and 43 +/- 10. The 6-h elimination half-life of ceftriaxone was 2- to 10-fold longer than those reported for marketed and other known investigational cephalosporins. The small dose-related increases in the apparent volume of distribution and clearance parameters can be explainhe 48-h urine samples, 41 +/- 8, 39 +/- 5, and 43 +/- 10. The 6-h elimination half-life of ceftriaxone was 2- to 10-fold longer than those reported for marketed and other known investigational cephalosporins. The small dose-related increases in the apparent volume of distribution and clearance parameters can be explained by the concentration-dependent plasma protein binding of ceftriaxone in humans. The impact of the small dose-dependent changes in the pharmacokinetics of ceftriaxone is anticipated to be of negligible clinical significance.

Adult↗

Nonlytic simian virus 40-specific 100K phosphoprotein is associated with anchorage-independent growth in simian virus 40-transformed and revertant mouse cell lines.

Normal fibroblasts display two distinct growth controls which can be assayed as requirements for serum or for anchorage. Interaction of mouse 3T3 fibroblasts with simian virus 40 (SV40) thus generates four classes of transformed cells. We have examined viral gene expression in these four classes of cell lines. Immunoprecipitation of [35S]methionine-labeled cell extracts with an antiserum obtained from tumor-bearing hamsters detected the SV40 large T and small t proteins (94,000 molecular weight [94K], 17K) and the nonviral host 54K protein in all cell lines tested. A tumor antigen with an apparent molecular weight of 100,000 was also found in some, but not all, lines. Similar "super T" molecules have been found by others in many rodent transformed lines. We carried out an analysis of the relation of phenotype to relative amounts of these proteins in cell lines of the four classes, using the Spearman rank correlation test. The amount of the 100K T antigen relative to the 94K T antigen or to total viral protein was well correlated with the ability to form colonies in semisolid medium. No significant correlation was found between quantities of labeled 94K T antigen, 54K host antigen, or 17K t antigen and either serum or anchorage independence. Mouse cells transformed with the small t SV40 deletion mutant 884 synthesized a 100K T antigen, suggesting that small t is not required for the production of this protein. The 100K T antigen migrated more slowly than lytic T. Since mixtures of extracts from cells expressing and lacking the 100K T antigen yielded the expected amount of this protein, it is unlikely that the 100K T derives from the 94K protein by a posttranslational modification.

Animals↗

Plasticity of synaptic size with constancy of total synaptic contact area on Purkinje cells in the cerebellum.

Reduction of Purkinje cell afferents during development or after maturation resulted in a large change in the size of synaptic contacts on dendritic spines. Ultrastructural studies revealed enlarged Purkinje cell spines and elongation of the synapses with parallel fibers in three models of parallel fiber reduction: 1) developmental malnutrition, 2) developmental virus-induced granule cell reduction, and 3) parallel fiber sectioning in the adult. In developmental malnutrition, five groups of animals having different numbers of parallel fiber afferents to Purkinje cells, but the same total number of these cells, were quantitatively compared. As the number of synaptic junctions on Purkinje cells decreased, average area of synaptic contact increased. From this determination, it was further established that the total contact area on each Purkinje cell remained constant for groups of animals having different levels of afferent reduction. This inverse relationship was the result of Purkinje cells having a constant total synaptic contact area for parallel fibers. These studies show that the total postsynaptic area for each Purkinje cell is intrinsically determined and that synapses with the remaining parallel fibers change their size in a plastic response to interactions between pre- and postsynaptic elements.

Afferent Pathways↗

The replication pattern of adenovirus DNA in vivo reproduced in vitro.

Temperature-sensitive mutants of adenovirus type 5 (H5ts125 and H5ts149), which are conditionally inhibited in the initiation of viral DNA synthesis, have been exploited to investigate the possibility of the initiation of replication in a cell-free system. Nuclei were isolated from human KB cells which had been infected with wild-type or mutant adenovirus. More than 90% of the DNA synthesis taking place in such nuclei was virus-specific and the pattern of drug inhibition suggested that the synthesis required DNA polymerase gamma. Nuclei prepared from cells infected with the H5ts125 temperature-sensitive mutant which have been shifted from 33 degrees C to 39.5 degrees C showed a pattern of synthesis in vitro which began at both ends of the viral genome and gradually spread through the rest of the molecule.

Adenoviruses, Human↗

Effects of Diesel engine exhaust on pulmonary alveolar macrophages.

The in vivo effects of inhalation of diesel engine exhaust (DEE) on pulmonary alveolar macrophages (PAM) was studied in 73 guinea pigs and 48 rats. Animals were exposed in individual cages in special chambers to 3 different dose levels of DEE expressed in terms of the concentation of soot or carbon particles (-P); 250, 1500, 6000 micrograms DEE-P/M3. Exposure durations for guinea pigs were 1 and 3 days, 1 and 2 weeks, 2, 4, 8 and 12 months while rats were exposed 1, 2, 4, 8 and 12 months. Age matched controls were similarly exposed concurrently to "clean" air. PAM obtained by bronchopulmonary lavage from exposed animals had viabilities comparable to controls. PAM diameters and relative surface areas increased 2--3 fold over controls and in relation to both the dose of DEE-P given and the exposure duration. Most of the in vivo exposed PAM had phagocytized DEE-P which did not appear to be cytotoxic and remained confined in phagosomes as discrete particles with diameters of 0.014--0.072 micrometer. Ability of PAM to adhere and spread on test surfaces was greater in the DEE-P sets than in controls. DEE-P containing PAM were still able to phagocytize latex particles when fed in vitro. However, such PAM had defective phagocytosis ability, and did not in the same time interval take up as much fluorescent latex as controls when studied by flow system technology. Absolute numbers of PAM in guinea pig lavages from exposures to 250 and 1500 microgram DEE-P/M3 for 2 months were not significantly changed over concurrent controls. Exudative leukocytes (eosinophils in guinea pigs and neutrophils in rats) appeared in the lavage in greater numbers as dose and duration of exposure increased. Another species difference was the appearance in DEE-P exposed guinea pig lavages of "reactive" monocytes.

Animals↗