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H Cheng

Publications and source records attributed to H Cheng.

At least 487 records · Page 27Linked to original sources
PubMed1983

Pharmacokinetics of 5,6-dihydro-5-azacytidine (NSC-264880) in the foxhound.

An HPLC analytical method was applied to the determination of plasma concentrations of 5,6-dihydro-5-azacytidine (NSC 264880, DHAC) in two foxhounds after a rapid intravenous infusion of 300 mg/kg DHAC. The dose employed is the mouse equivalent LD10 dose which results in mild reversible toxicity in the dog. The decline in DHAC plasma concentrations was greater than three log decades after dosing. The plasma concentration-time data was computer-fitted by NONLIN to a three compartment open model with first-order elimination using the equations for a short intravenous infusion. The half-lives corresponding to the three exponential phases were: t1/2 alpha = 5.78 min, t1/2 beta = 1.57 h and t1/2 gamma = 22.0 h in dog 1 and t1/2 alpha = 7.41 min, t1/2 beta = 2.25 h and t1/2 gamma = 21.6 h in dog 2. The terminal phase of the plasma concentration time profiles represented a minor contribution (2.2-3.2%) to the total area under the curve. The plasma concentration time data for the first 12 h after dosing was computer fitted to a two compartment open model. The initial and terminal half-lives determined from the two compartment fits were similar to the t1/2 alpha and t1/2 beta values of the fits to the three compartment open model. Similar total body clearance values were calculated from the areas under the plasma concentration time curves from time zero to infinity for the computer fits to the three and two compartment models, respectively. Thus, for practical purposes, it appears feasible to define adequately the total body clearance of DHAC by analysis of the plasma concentration time data during the time interval in which the plasma concentration is described as a bi-exponential equation. Renal excretion of the parent drug is the principal route of excretion of DHAC from the dog.

Animals↗
PubMed1983

Intraocular lenses.

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Aphakia, Postcataract↗
PubMed1982

Cell flux through S phase in the mouse duodenal epithelium determined by cell sorting and radioautography.

An accumulation of cells in early S phase was observed in normal mouse duodenal epithelium studied with flow cytometry (Cheng and Bjerknes, 1982). To determine if this accumulation of cells was the result of a lower rate of DNA synthesis, animals were given a single injection of 3H-thymidine and the epithelium collected one hour later. The epithelium was processed for flow cytometry. Seven sort windows were established in different portions of the DNA histogram. Cells from each window were sorted onto glass slides that were then processed for radioautography. The number of silver grains over the nuclei of each sorted population was counted. It was found that cells in early S phase had significantly fewer grains over their nuclei than did mid- or late-S phase cells. We conclude that the accumulation of cells in early S phase is due, at least in part, to a lower rate of DNA synthesis in early than in mid or late S phase.

Animals↗
PubMed1982

Plasminogen activator activity in human prostate and breast tumors: relationship to steroid receptors.

Using a fluorometric assay based on the activation of human plasminogen, plasminogen activator (PA) activity was measured in cytosolic and lysosomal extracts prepared from normal, benign hyperplastic (BPH), and carcinomatous human prostates. In all three types of prostatic tissue, the lysosomal extracts had much higher concentrations of PA activity than did the cytosolic extracts. The mean PA activity in lysosomal extracts of the carcinomatous prostates was 170% and 85% higher than that measured in normal and BPH prostates, respectively (Student's t-test, p less than .05). With prostatic carcinoma and BPH specimens there was an inverse (negative) relationship between lysosomal PA activity and the nuclear concentration of androgen-receptors (correlation coefficient, -0.84). By comparison in specimens of human breast tumors, there were weakly positive correlations between PA activity and either estrogen (ER) or progestin (PR) receptors (correlation coefficients of + 0.23 and + 0.54, respectively). While as a group ER+, PR+ breast tumors had higher PA activity that ER+, PR- or ER-, PR- tumors, the differences were not statistically significant (Student's t-test, p greater than .05). Thus in breast tumors, it is uncertain whether high levels of PA activity are indicative of hormonal dependence. However, our findings with prostatic tumors infer that in contrast, high concentrations of this enzyme may reflect a malignant phenotype characterized by a decrease in both androgen responsiveness and differentiation.

Aged↗
PubMed1982

Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests.

The affinities of dothiepin and its principal metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide for [3H]imipramine binding sites in the rat cortical homogenates, and for [3H]spiperone and [3H]serotonin receptor sites in preparations from the rat frontal cortex and hippocampus were studied. As inhibitors of [3H]imipramine binding, the strengths of the drugs are, in terms of their IC50 (concentration corresponding to 50% inhibition): dothiepin 2.8 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 4.0 X 10(-5) M and dothiepin sulphoxide 3.2 X 10(-5) M. The potencies of the drugs in inhibiting serotonergic binding followed a similar trend. Using frontal cortical tissue suspensions and [3H]spiperone, the IC50 values were determined to be: dothiepin 4.2 X 10(-6) M, northiaden 5.0 X 10(-6) M, northiaden sulphoxide 1.6 X 10(-4) M and dothiepin sulphoxide 1.6 X 10(-4) M; whereas in hippocampal suspensions and using [3H]serotonin, the IC50 values were 2.5 X 10(-6) M, northiaden 4.0 X 10(-5) M, dothiepin sulphoxide 2.5 X 10(-4) M and northiaden sulphoxide greater than 10(-3) M. The influence of the drugs on the uptake of [14C]serotonin into human platelets was also investigated. All had an inhibitory effect upon the uptake, the order of potency being dothiepin greater than northiaden greater than northiaden sulphoxide greater than dothiepin sulphoxide. Plots of 1/v versus 1/s showed that the inhibition was competitive for all four compounds.

Animals↗
PubMed1982

Rate of endothelial cell loss in the early postoperative period after cataract surgery.

Central corneal endothelial cell density was estimated in 33 consecutive patients preoperatively and at monthly intervals for 6 months after cataract surgery. The patients were divided into 3 groups by a random procedure to have either intracapsular extraction or intracapsular extraction plus Federov 4-loop iris clip lens, or extracapsular extraction with Binkhorst 2-loop iridocapsular lens. In all groups the greatest cell loss had occurred by one month and thereafter no accelerated loss was apparent except in individual patients. The limitations of such a method of assessment are discussed.

Aged↗
PubMed1981

The stem-cell zone of the small intestinal epithelium. I. Evidence from Paneth cells in the adult mouse.

Stem cells in the small intestinal epithelium are known to differentiate into columnar, mucous, enteroendocrine, and Paneth cells. However, the site of initiation of stem-cell differentiation has been unknown. To approach this problem we determined the site of stem-cell differentiation along the Paneth cell line, using light microscopic morphometry and radioautography. The smallest Paneth cells containing the smallest granules were in positions 6 and 7, while the largest ones containing the largest granules were in positions 1 and 2 at the base of the crypt. Paneth cell death was less prevalent above position 3 than it was in position 1. Since cell size, granule size, and cell death are indicators of Paneth cell age, it was deduced that there is a gradient of Paneth cell age in the crypt base, with the oldest Paneth cells at the bottom, and the youngest at the top. After single injection or continuous infusion of 3H-thymidine, the first labeled Paneth cells to appear were the highest Paneth cells in their crypt column. Later, labeled Paneth cells became more prevalent in lower positions, and, eventually, appeared in position 1. The size of granules in labeled Paneth cells increased with time. It was concluded that Paneth cells originate in position 5 or above and then migrate downward. These results are consistent with a stem-cell zone hypothesis, which proposes that stem cells in positions 1-4 receive no inducement to differentiate. Only those stem cells that migrate up out of the stem-cell zone into position 5 will be induced and then begin to differentiate.

Animals↗
PubMed1981

The stem-cell zone of the small intestinal epithelium. II. Evidence from paneth cells in the newborn mouse.

The restriction of Paneth cell formation to the top of the Paneth cell distribution in the adult was suggested to be due either to the existence of a stem-cell zone or to the influence of a Paneth cell population-density gradient (Bjerkness and Cheng, 1981). To distinguish between the two possible mechanisms, the development of the Paneth cell distribution in neonatal mice (0-10 days old) was studied. If restricted formation were due to the presence of a population-density gradient of Paneth cells, then in neonatal animals, in the absence of a Paneth cell population-density gradient, Paneth cell formation would occur throughout the crypt base. If, on the other hand, restricted formation were due to the presence of a stem-cell zone, and if this mechanism were operative in the newborn, Paneth cell formation in the newborn would be restricted to the region above the stem-cell zone. The position of each Paneth cell within the crypt, and the size of its largest granule, were recorded. On day 0, Paneth cells were present, but crypts were poorly developed and positional assignment was not possible. On day 1, immature crypts developed. All Paneth cells found in immature crypts on day 1 were at the crypt-surface junction (approximately position 5). On day 2, most Paneth cells were at the crypt-surface junction. Thereafter, Paneth cells began to appear at lower positions. On day 3, there were 15 times more Paneth cells in position 5 than in position 1. On day 4, there were still three times more Paneth cells in position 5 than in position 1. With age, the proportion of Paneth cells in position 1 increased while that in position 5 decreased. On day 10 there were more Paneth cells in position 1 than in 5. At all time intervals, granules of Paneth cells in position 1 were significantly larger than those in position 5, indicating that Paneth cells in position 1 were older than those in position 5. It was concluded that in the neonate, before the establishment of a Paneth cell population-density gradient, Paneth cell formation was restricted to positions 5 and above. This supports the existence of a stem-cell zone, not a Paneth cell population-density gradient, as the underlying mechanism of restricted Paneth cell formation in the adult.

Aging↗
PubMed1981

The stem-cell zone of the small intestinal epithelium. III. Evidence from columnar, enteroendocrine, and mucous cells in the adult mouse.

In the first two articles of this series we demonstrated restriction of Paneth cell formation to positions 5 and above. Restriction was independent of the Paneth cell population-density gradient in the crypt base. We concluded that our results were consistent with the presence in the adult of a stem-cell zone in positions 1-4 in which stem cells received no inducement to differentiate. To further test the stem-cell zone hypothesis we determined the site of stem-cell differentiation along mucous, enteroendocrine, and columnar cell lines using radioautography with 3H-thymidine as a label. One hour after injection of 3H-thymidine, labeled mucous cells were not observed below position 5. Only later did they appear in lower positions and not until 4 days after injection were they observed in position 1. Labeled enteroendocrine cells first appeared above, and then were seen in the top of, and finally in the middle and bottom of the Paneth cell distribution. Thirty hours after injection there were two populations of labeled columnar cells in the crypt base, a heavily labeled population and a lightly labeled one. At this time interval the heavily labeled columnar cells were only observed in positions 5 and above, but they appeared in positions 1-4 by 66 hours after injection. The above evidence led us to conclude that all differentiated offspring of the common epithelial stem cell originate in positions 5 and above. Most columnar, mucous, and enteroendocrine cells originating in positions 5 and above migrate upward. However some of these cells migrate down. All differentiated cells found in positions 1-4 migrated down from their origin in position 5 or above. We also found that only stem cells proliferate in positions 1-4. We concluded that in the adult, there is a stem-cell zone in positions 1-4 where stem cells are not induced to differentiate and persist as stem cells throughout life.

Animals↗
PubMed1981

The stem-cell zone of the small intestinal epithelium. IV. Effects of resecting 30% of the small intestine.

In the mouse jejunum, as in the rat, a new steady state was established 3 weeks after resection of 30% of the small intestine. The mean height of a villus, crypt, and proliferative zone increased. We studied the effects of this new steady state on the distribution of the four main epithelial cell types and on the stem-cell zone. Beginning 2 cm distal to the ligament of Treitz, 10 cm of jejunum were resected. In control animals the jejunum was transected 12 cm distal to the ligament of Treitz and then rejoined. The mice were killed 1 and 3 weeks after surgery and a piece of jejunum 4 cm distal to the anastomosis collected. One hour before death the animals were given an injection of 1 mu Ci/gm 3H-thymidine. The tissue was embedded in Epon and then serial 1 micron sections were prepared and radioautographed. One week after resection there was a transient increase in the proportion of enteroendocrine cells in the crypts. This returned to control levels 3 weeks after resection. Thus, there appeared to be a feedback from the enteroendocrine population onto enteroendocrine cell production. After resection, amplification of mucous cell numbers by mucous cell division was reduced and yet normal proportions of mucous cells were observed in the epithelium. Therefore, an increased proportion of stem-cell output must have been committed to the mucous and enteroendocrine cell lines. The increased height of the proliferative zone that followed 30% resection was not due to an increase in the number of transit divisions through the proliferative zone. Instead it was due to an increased output from the stem-cell zone into the proliferative zone. Evidence was presented which indicates that the increased output from the stem-cell zone was due to an increased number of stem cells in the zone, at the expense of non-stem cells. The height of the stem-cell zone, as indicated by the Paneth cell distribution, the mucous cell distribution, and the distribution of labeled mucous cells, did not change after 30% resection.

Animals↗
PubMed1981

Estimating pA2 values for different designs.

The method for analyzing data leading to the estimation of a pA2 depends on the experimental design. Three different experimental designs are discussed. For each design, we provide a brief description of experimental situations that give rise to the design, a means for verifying relevant assumptions, and sample data with summary calculations.

Animals↗