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Biomedical subjects

P Coyle

Publications and source records attributed to P Coyle.

At least 73 records · Page 4Linked to original sources
PubMed1985

alpha-1-Antitrypsin metabolism in the protein-deficient weanling rat.

Protein-deficient weanling rats fed on a 30 g casein/kg diet for 3 weeks lost albumin but maintained the level of serum alpha-1-antitrypsin, the most abundant protease inhibitor in blood. alpha-1-Antitrypsins from malnourished rats and control rats (given 250 g casein/kg diet) differed; the protease inhibitor from protein-deficient animals: (1) was more acidic, (2) appeared slightly larger (57 400 v. 56 000 daltons) on sodium dodecyl sulphate (SDS)-polyacrylamide gels, (3) had a more acidic Pi type and increased anodal mobility at pH 8.9, (4) bound more concanavalin-A and contained more carbohydrate, specifically two to three extra sialic acid residues. The amino sugar and neutral sugar contents of both preparations of alpha-1-antitrypsin were the same. Analysis of the products of cyanogen-bromide cleavage revealed that alpha-1-antitrypsin preparations from protein-deficient rats contain an extra glycopeptide that was not present in alpha-1-antitrypsin from control animals. In vivo studies showed that the increased sialic acid content of alpha-1-antitrypsin of protein-deficient rats did not alter the half-life of the molecule in the blood of control rats. However, the fractional catabolic rate of alpha-1-antitrypsin from either well-nourished or protein-deficient rats was significantly (P less than 0.01) lower in protein-deficient rats than in control rats (0.0247/h v. 0.0406/h). The decreased fractional catabolic rate could not be explained by changes in hepatic mannosyl-, galactosyl- or N-acetylhexosaminyl receptors since liver perfusion studies showed that bovine serum albumin, when covalently modified separately with each of these ligands, was extracted from the perfusion medium as rapidly or more rapidly by livers from malnourished animals. Perfused livers from protein-deficient rats secrete three times more alpha-1-antitrypsin than do livers from well-nourished animals. The decreased fractional catabolic rate and increased rate of biosynthesis and secretion of the glycoprotein by livers from protein-deficient animals may account for the maintenance of alpha-1-antitrypsin levels during protein malnutrition.

Albumins↗
PubMed1984

Diameter and length changes in cerebral collaterals after middle cerebral artery occlusion in the young rat.

Rapid occlusion of the middle cerebral artery (MCA) in the 36-day-old normal Wistar rat results in change of the dorsal collaterals joining branches of the anterior and middle cerebral arteries. As compared to similarly positioned vessels on the opposite hemisphere and arterioles in unoperated rats of 56 days of age, there were significantly (P less than 0.001) more large (60-120 microM) diameter collaterals on the occluded side 20 days after MCA occlusion. There were fewer small (0-59 microm) diameter collaterals on the occluded side as compared to unoperated rats. The data suggest small diameter arterioles existing at occlusion became large diameter collaterals. The mean number of collaterals per hemisphere was not significantly different (P greater than 0.05) between occluded and unoperated rats. There was no evidence that new vessels were added during the 20-day ligation period. The mean collateral tortuosity value was significantly (P less than 0.01) greater for large diameter vessels on the right occluded side as compared to vessels on the left hemisphere or vessels in unoperated age-matched control rats. The greater tortuosity values of vessels on the occluded side were evidence that collateral vessel length was increased by 24-29% after MCA occlusion. Speculation was made about possible mechanisms responsible for these vascular changes.

Animals↗
PubMed1982

Dorsal cerebral arterial collaterals of the rat.

This study demonstrated that distal branches of the anterior cerebral artery (ACA) are joined by interarterial anastomoses to rami of the middle cerebral artery (MCA) in the normal Wistar rat. Arteries of 36- and 56-day-old animals were dilated with papaverine and injected with Vultex. Vultex arrived at corresponding ACA and MCA collaterals simultaneously as determined by microscopy through a skull window and photography. There were about 29 ACA-MCA junctions per hemisphere. Junction density was nearly constant along the frontal-occipital axis. The anastomoses were most numerous between 2 and 3 mm lateral to the midline and were less than 120 micron in internal diameter. No significant difference was found between total numbers of junctions for right versus left hemispheres or between age groups. The most evident collateral pattern was characterized by two ACA end rami joining two MCA end branches to form a closed, diamond-shaped collateral unit. Considerations were given to alternate routes of blood flow into the MCA tissue field. We conclude abundant dorsal anastomoses exist in 36- and 56-day-old rats and are the prime potential source for ACA collateral supply to the MCA tissue field.

Age Factors↗
PubMed1977

Purification and properties of a heat-stable glucocerebrosidase activating factor from control and Gaucher spleen.

Gaucher's disease is a lysosomal storage disease caused by a deficiency in the enzyme glucocerebrosidase. A small, heat-stable glycoprotein first obtained from Gaucher spleen (Ho, M. W., and O'Brien, J. S. (1971) Proc. Natl. Acad. Sci. U. S.A. 68, 2810-2813) has been observed to stimulate the activity of glucocerebrosidase isolated from normal tissue. It has been suggested that this material might be important in the physiological catabolism of glucocerebroside in normal individuals (Ho, M. W. (1974) in Enzyme Therapy in Lysosomal Storage Diseases (Tager, J. M., Hooghwinkel, G. J. M., and Daems, W. Th., eds) pp.239-246, North-Holland Publishing Co., Amsterdam). In order to investigate this suggestion, glucocerebrosidase activating factors were isolated and purified from control and Gaucher spleen and characterized. Although approximately the same mass of activator was isolated from both spleens, the two activators differ from one another in a number of important respects: (a) the activator from the control spleen is only 6 per cent as active (on a protein basis) as the activator from Gaucher spleen; (b) the amino acid compositions of the purified activators are significantly different; and (c) carbohydrate analysis of the purified activators indicates that the activator from Gaucher spleen is a glycoprotein, while that from control spleen is not. Comparative kinetic studies demonstrate that the anionic detergent, sodium taurocholate, and the acidic phospholipid, phosphatidylinositol, both stimulate glucocerebrosidase activity to a larger extent than the activator substance from Gaucher spleen. The activator from Gaucher spleen and human liver glucocerebrosidase both appear to contain significant hydrophobic character. We conclude that the activator is probably not physiologically important in the catabolism of glucocerebroside in normal tissues. The significance of the occurrence of this apparently unique glycoprotein activator in Gaucher spleen remains obscure; however, its presence represents another interesting aspect of Gaucher's disease that warrants further investigation.

Amino Acids↗
PubMedDate not supplied

Outcomes to middle cerebral artery occlusion in hypertensive and normotensive rats.

To ascertain whether infarction and noninfarction outcomes to rapid occlusion of the middle cerebral artery (MCA) are differentiated by alteration of the systolic blood pressure (BP), rats under the following conditions were tested: normal Wistar rats (NW) made acutely hypertensive with deoxycorticosterone acetate (DOCA)-salt, spontaneously hypertensive stroke-prone rats (SHRSP) receiving captopril antihypertensive medication for 7 weeks, and SHRSP with captopril withdrawn 2 weeks prior to the occlusion test. Eleven of 13 acutely DOCA-salt hypertensive NW were protected from infarction. Adequate collateral circulation was preserved in NW vessels initially formed under normotensive conditions but tested during acute DOCA-salt hypertension. Since all SHRSP tested had infarcts, SHRSP were more susceptible to infarction than NW made acutely DOCA-salt hypertensive. SHRSP with captopril medication withdrawn for 2 weeks had higher BP and larger infarcts than SHRSP maintained on the drug. Results suggest that the mechanism causing elevated BP or one secondary to it adversely alters the collateral supply in SHRSP. An increase in collateral vascular resistance initiated during anatomical development of the anastomoses very early in life may predispose SHRSP to infarct after rapid MCA occlusion later in life.

Animals↗
PubMedDate not supplied

Middle cerebral artery occlusion in the young rat.

This investigation describes a surgical approach for ligation of the middle cerebral artery (MCA) in the young rat and evaluates consequences of the occlusion with a neurologic exam for motor deficits, Evans blue test for blood-brain barrier leaks, and light microscopy for histologic changes after 3 days. Evans blue extravasation and the lesion were limited to cortex at the burr hole site in occluded and sham operated rats. MCA occlusion beyond the point of origin of the striate branches in the young rat results in neither neurological deficits, dye markings, nor histologic changes in the distal vascular field to indicate an infarct. Apparently, the young rodent collateral supply maintains the tissue in a viable state.

Animals↗
PubMedDate not supplied

Differential outcome to middle cerebral artery occlusion in spontaneously hypertensive stroke-prone rats (SHRSP) and Wistar Kyoto (WKY) rats.

Evidence was found for different outcomes to middle cerebral artery occlusion in the young genetically hypertensive stroke-prone rat (SHRSP) compared to sham operated controls and the Wistar Kyoto rat (WKY). Qualitatively and quantitatively different gross lesions marked by Evans blue-albumin, cortical atrophy, large areas of strikingly altered cortical histology, postoperative survival and motor behavioral deficits differentiate young SHRSP from sham operated controls and the normotensive WKY. We conclude that the limited focal lesion observed in normotensive and sham operated rats is primarily due to surgical trauma of exposing the vessel and passing the ligature deep to it. The grossly larger and qualitatively different lesion in the SHRSP is the result of an inadequate circulation provided by the dorsal cerebral arterial collaterals. Since the 5-6 week old SHRSP were only mildly hypertensive (systolic blood pressure 140 mm Hg), the inadequate collateral circulation appears to be related to either a genetic or acquired problem rather than being secondary to a vascular lesion of chronic hypertension.

Animals↗
PubMedDate not supplied

Cerebral infarction after middle cerebral artery occlusion in progenies of spontaneously stroke-prone and normal rats.

A differential outcome results from rapid middle cerebral artery (MCA) occlusion in young normotensive Wistar (NW) rats as compared to the spontaneously hypertensive stroke-prone (SHRSP) rat. The SHRSP invariably infarcts; the NW usually does not. To determine if segregation at a single autosomal locus explains the difference between strains, a NW male was crossed with several SHRSP females to produce F1 rats. The segregation of the strain difference was studied in the F2 and backcrosses to the NW and SHRSP parental strains. The relative frequency of infarcting and noninfarcting animals in the segregating progenies supported a single locus recessive model of inheritance for susceptibility to infarction after sudden occlusion of the MCA. Mean infarct size was largest for SHRSP and proportional to the SHRSP gene dosage in the segregating progenies. Variation in the size of the infarct within segregating classes may be attributable to the segregation of polygenes and/or environmental influences during the initial formation of the cerebral anastomoses.

Animals↗