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Biomedical subjects

L McCoy

Publications and source records attributed to L McCoy.

17 recordsLinked to original sources
PubMed1991

Beneficial effects of isovolemic hemodilution using a perfluorocarbon emulsion in a stroke model.

In a clinically applicable cat stroke model, 16 purpose-bred adult animals were used to evaluate the beneficial effects of two treatment regimens: isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 (a glucose polymer). Animals that received these treatment regimens were then compared with a control group of untreated animals. Focal cerebral infarctions were produced by transorbital ligation of the left middle cerebral artery. The randomly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery, thereby simulating a human clinical situation. In vivo mitochondrial metabolic activity of the peri-infarct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer. This allowed measurement of cellular oxygenation at the cytochrome aa3 level, the terminal member of the cytochrome chain. Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo. Cardiac output, oxygen consumption/delivery, chemical, histologic, and rheologic parameters were also assessed. The data collected were analyzed by group means and standard statistical analyses, which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infarct period (p less than 0.05), as well as a higher level of oxidation of cytochrome aa3 (p less than or equal to 0.025). This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes.

Animals↗
PubMed1988

Development of bronchiolar epithelium: time course of response to oxygen and recovery.

Hyperoxia (greater than 95% O2) reversibly suppresses the early postnatal development of rat bronchiolar epithelium. We now show that blunting of the normal increase in nuclear numerical density per centimeter cubed of Clara and ciliated cells becomes apparent within 24 h of exposure to O2 (age 2 days) and reaches a maximum on the last day of hyperoxia (age 7 days). The intergroup differences began to disappear within 48 h after removal from O2. During air breathing, Clara cell mitosis increased sixfold between the ages of 1 and 2 days and returned to day 1 values by age 7 days. During O2 breathing, Clara cell mitosis increased threefold between age 1 and 2 days, returned to day 1 values by day 4, but exhibited a second peak 24 h post-O2 (day 8) not present in unexposed pups. The onset of differences in the volume of Clara cell organelles and glycogen was variable, but the differences were partly or completely eliminated 48 h post-O2 exposure. We conclude hyperoxia reversibly impairs mitosis by Clara cells.

Animals↗
PubMed1988

Postnatal undernutrition slows development of bronchiolar epithelium in rats.

The lung's small conducting airways are sites of dysfunction early in the course of chronic lung diseases that are prevalent in humans; furthermore, there is evidence that aspects of childhood environment may adversely influence small airway function in adulthood. Because there is considerable early postnatal morphological maturation of the bronchiolar epithelium in rats, these considerations led to the present study in which we assessed the effect of early postnatal undernutrition in rats on the anatomic development of the bronchiolar epithelium. We found undernutrition, produced by increasing rat litter size shortly after birth, led to delayed development of the mitochondria and rough endoplasmic reticulum of bronchiolar Clara cells. Of particular interest, underfeeding resulted in considerably diminished mitosis by Clara cells, decreased nuclear numerical density of bronchiolar ciliated cells, evidence of diminished conversion of Clara cells to ciliated cells, and an abnormal cellular composition of the small airway epithelium that persisted well beyond the period of underfeeding. We conclude that early neonatal events can have long-term effects on the bronchiolar epithelium.

Aging↗
PubMed1986

Biogenesis and cell cycle relationship of poly(A)- actin mRNA in mouse ascites cells.

A variety of rapidly growing mammalian cells contain a substantial portion of their actin mRNA in a poly(A)- form. We have used DNA-driven hybridization of a cloned actin cDNA-containing plasmid with pulse-labeled RNA from mouse S-180 ascites cells to examine newly synthesized actin mRNA. Our results indicate that the same proportion of newly synthesized and steady-state actin mRNA (approx. 40%) exists in a poly(A)- deficient form. This suggests that the poly(A)- form arises by some process other than slow cytoplasmic de-adenylation of a poly(A)+ precursor. We have also examined cell cycle-enriched populations of S-180 ascites cells for the presence of poly(A)- actin mRNA. Results from these experiments indicate that cells in G1 phase of the cell cycle contain predominantly poly(A)+ actin mRNA, while the poly(A)- form is restricted to late-S and post-S phase cells.

Actins↗
PubMed1986

Hyperoxia reversibly suppresses development of bronchiolar epithelium.

The bronchiolar epithelium of rats is anatomically immature at birth. We now ask whether postnatal hyperoxia impairs the normal development of bronchiolar epithelium; and, if development is impaired, is the impairment permanent? To answer these questions, we exposed newborn rats to hyperoxia (greater than 95% O2, 1 atm) or air for 7 days and killed the rats at age 7 or 30 days. We used ultrastructural and morphometric means to assess maturation of the bronchiolar epithelium. Hyperoxia substantially diminished the postnatal increase in nuclear numerical density of bronchiolar Clara cells and ciliated cells. Hyperoxia also markedly delayed the rise in volume density of Clara cell secretory granules and rough endoplasmic reticulum but accelerated the increase in volume density of Clara and ciliated cell mitochondria. When rats exposed to hyperoxia from age 1 to 7 days were thereafter allowed to breathe air, by age 30 days all the differences were eliminated that were detected between the air- and O2-breathing groups at age 7 days. We conclude hyperoxia causes a marked but nonpermanent suppression of maturation of the bronchiolar epithelium.

Aging↗
PubMed1985

Determination of fezolamine and its desmethyl metabolite in human plasma and urine by high-performance liquid chromatography. Intravenous pharmacokinetics in the beagle hound.

Sensitive and selective high-performance liquid chromatographic methods for the quantitation of the experimental antidepressant fezolamine and its desmethyl metabolite in plasma and urine have been developed. Both assays are linear between 0 and 500 ng/ml in both plasma and urine and have calculated minimum quantifiable levels of less than 10 ng/ml. Statistical evaluation of analytical parameters under single-blind conditions demonstrated an overall precision within +/- 4% of nominal for both compounds in either biological medium. The overall accuracies of the assays were within +/- 5% of nominal values in urine and +/- 10% of nominal values in plasma. Following intravenous administration of fezolamine fumarate to beagle hounds, a biexponential decline in drug plasma levels was observed with the first phase having a half-life of about 11 min and the second phase about 2.6 h. Peak plasma levels of the metabolite were observed at 2 h. Recovery of the parent drug in urine was less than 5% of the administered dose and less than 1% for the desmethyl metabolite.

Animals↗
PubMed1980

Value of serial CEA determinations in a surgical adjuvant trial of colorectal and gastric carcinoma.

At the Cross Cancer Institute in Edmonton, a concurrently controlled, randomized, prospective surgical adjuvant trial involving Dukes' B2 and C colorectal carcinoma and gastric carcinoma (T1-4, No-2, Mo) has been activated for the last two years. To date, a total of 150 patients have been entered into the three arms of the trial (namely control, immunotherapy, and chemoimmunotherapy). Of these, 127 cases are colorectal carcinoma and 28 are gastric cancer. As part of the protocol, serial CEA determinations are obtained in all patients on a regular three-monthly basis. So far, 28 patients have confirmed recurrence (colorectal 20, gastric 8) demonstrated clinically or radiologically. Out of these 28 patients, 25 (89.2%) had CEA greater than 2.5 ng/ml months before actual demonstration of recurrence. However, if one uses a cutoff of 5.0 ng/ml as significant, that is, one standard deviation from the usual accepted value, then 21 out of 28 (75%) had persistent, elevated CEA's months before the recurrence manifested itself clinically or radiologically. The CEA profiles of three representative cases from each arm of the adjuvant trial are included. It is suggested that serial CEA determinations will be an invaluable adjunctive test in following patients in an adjuvant trial setting.

Carcinoembryonic Antigen↗