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P Coyle

Publications and source records attributed to P Coyle.

At least 55 records · Page 3Linked to original sources
PubMed1993

Risk area and infarct area relations in the hypertensive stroke-prone rat.

BACKGROUND AND PURPOSE: Our purpose was to characterize the surface area of the infarct and the surface area at risk of infarction as defined spatially by arterial anastomoses to determine whether position, size, or shape of the infarct and the area at risk were related in stroke-prone rats or hybrid rats. METHODS: Stroke-prone rats (n = 18; mean +/- SEM blood pressure, 182 +/- 8 mm Hg) and hybrid rats (n = 18; mean +/- SEM blood pressure, 147 +/- 6 mm Hg; p < 0.05) were anesthetized and the left middle cerebral artery was occluded with a ligature. The rats were killed 7 days later, arterial anastomoses were made visible with latex, the brains were fixed in formalin, and film recorded the infarct and anastomoses. Anastomoses and infarcts were digitized for measurements of risk area, luminal width, and infarct area. RESULTS: Mean risk area was similar in size, length, width, and variability in stroke-prone rats (area, 85 +/- 5 mm2) and hybrid rats (area, 84 +/- 7 mm2; p > 0.05), whereas mean infarct area was larger, longer, wider, and less variable in stroke-prone rats (area, 53 +/- 6 mm2) than in hybrid rats (area, 15 +/- 11 mm2; p < 0.05). Infarct length was appreciably greater than infarct width in both groups, indicating that infarct shape was not amorphous. Spatial overlap maps indicated that the infarct area common to all stroke-prone rats was positioned centrally in the risk area and was surrounded by a variable infarct area, which indicated that the likelihood of infarction increased with distance from the anastomoses. Shape factors for both risk area and infarct area were significantly different within each rat group, which indicated that infarct shape did not uniformly parallel the anastomotic sites that determined risk area shape (p < 0.05). Risk area anastomoses and border zone width were linearly correlated in size and both were significantly wider in hybrid rats than in stroke-prone rats (p < 0.05), which suggests that the narrower border zone tissue was perfused by narrower anastomoses. CONCLUSIONS: We conclude that the position of the infarct within the risk area relates to luminal widths of conterminous anastomoses that define the risk area, but not to the size or shape of the area at risk of infarction defined spatially by the anastomoses.

Animals↗
PubMed1992

Changes in plasma zinc, copper, iron, and hepatic metallothionein in adjuvant-induced arthritis treated with cyclosporin.

The early changes in hepatic metallothionein (MT) and plasma zinc (Zn), copper (Cu), and iron (Fe) were investigated during the induction of adjuvant (AJ) arthritis in rats in conjunction with cyclosporin (CsA) treatment. Plasma Zn decreased after AJ injection (60% of control values at 8 h), and this was associated with a 4.5-fold increase in hepatic MT at 8 h. Plasma Zn was lowest at 16 h (40% of control), whereas hepatic MT concentrations increased to a maximum of 20-fold at 16 h. Changes in plasma Fe paralleled those of Zn, whereas plasma Cu levels were increased. Plasma metal and hepatic MT concentrations returned toward normal from d 1-7. At d 14, when marked paw swelling was apparent, hepatic MT and plasma Cu were again increased and plasma Zn decreased. Administration of CsA decreased MT induction in rats injected with AJ and also caused a marked recovery in plasma Zn and Fe levels. These changes were small but significant even in the early stages (up to 24 h) after AJ injection and were followed by a sustained improvement in all parameters, corresponding to the nonappearance of clinical arthropathy in CsA-treated rats. TNF-alpha and IL-6 production by peritoneal macrophages isolated from AJ-injected rats was significantly decreased by CsA treatment at d 7 and 14. The inhibition of hepatic MT induction during acute and chronic inflammation by cyclosporin emphasizes the role of the immune system in altered metal homeostasis in inflammation.

Animals↗
PubMed1992

Beneficial effects of endotoxin treatment on metabolism in tumour-bearing rats.

The effects of endotoxin treatment on host metabolism in tumour-bearing rats were investigated. Metabolism in control rats (non-tumour-bearing) was slightly altered by endotoxin treatment, whereas in tumour-bearing rats a number of biochemical parameters that were initially perturbed by the presence of the tumour had returned to normal at 48 h post-treatment. The beneficial effects included increased blood glucose and insulin concentrations, and decreased ketone body, triglyceride and lactate concentrations. Potentially non-beneficial effects of endotoxin observed in both tumour-bearing and control rats included decreased plasma cholesterol, and increased plasma phosphate, potassium and alkaline phosphatase levels. Endotoxin caused haemorrhaging in the encapsulated tumour, and this was associated with histological evidence of endothelial damage, red cell infiltration into surrounding tumour tissue and a marked decrease in cell viability. The in vivo uptake of glucose by the tumour, measured by 2-deoxy [U-14C]glucose uptake, was decreased by 96% following endotoxin treatment, and this was associated with a two-fold increase in glucose uptake by muscle. It is concluded that endotoxin treatment has major effects on cell viability and the integrity of vasculature in the tumour, which limits glucose uptake by the tumour and thereby decreases the energy and substrate requirements of the tumour, thus benefiting the host. It is suggested that tumour cytotoxicity and intra-tumour haemorrhage are the result of endotoxin stimulating cytokine release from macrophages that are already activated by the presence of the tumour.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Development of collaterals in the cerebral circulation.

Sudden occlusion of the middle cerebral artery (MCA) in normotensive rats increases blood flow through anastomosing branches into the territory of the occluded artery. Three weeks after MCA occlusion, anastomoses to anterior cerebral branches are increased by more than 50% in luminal diameter. One month after MCA occlusion, blood flow and blood flow reserve to the territory of the occluded MCA are returned to normal levels. In stroke-prone spontaneously hypertensive rats (SHRSP), the anastomoses are significantly narrower and blood flow through the anastomoses is less than in normotensive rats. Tissue infarction invariably develops in the territory of the occluded MCA in SHRSP. We propose that the luminal width of the anastomosis is a major determinant of blood flow into the territory of the occluded artery and of the amount of tissue protected from infarction by collateral circulation.

Animals↗
PubMed1990

Biochemical manifestations of a rat mammary adenocarcinoma-producing cachexia: in vivo and in vitro studies.

The physical and metabolic characteristics of a Dark Agouti rat mammary adenocarcinoma and its effects on host metabolism are described. The tumour was characterized by a lack of glandular differentiation, tetraploidy, a rapid mitotic index and a high rate of glycolysis. The adenocarcinoma was readily maintained in tissue culture and could be passaged through the host by inoculating either cell suspensions or tissue explants. In the rat, tumour growth resulted in a loss of adipose tissue at a tumour mass of less than 5% body weight indicating that increased energy expenditure was already present at that stage. In addition the tumour caused anaemia, hypercalcaemia and hypoglycaemia. Hyperketonaemia was also observed in fasted tumour-bearing rats. Methotrexate arrested tumour growth in vivo. These aspects of the tumour model make it useful for investigations into host-tumour competition and mechanisms of cachexia.

Adenocarcinoma↗
PubMed1990

Impaired dilatation of cerebral arterioles in chronic hypertension.

Several mechanisms impair cerebral vasodilatation during chronic hypertension. First, the external diameter of cerebral arterioles is reduced during chronic hypertension by structural 'remodeling'. Thus, both vascular hypertrophy and remodeling result in encroachment on the lumen. Second, endothelium-dependent dilatation of cerebral vessels is impaired during chronic hypertension. Third, blood flow through cerebral collaterals is impaired by chronic hypertension, so that an important compensatory mechanism is compromised. Impaired vasodilator responses, together with limitation of increases in collateral blood flow, may predispose to cerebral ischemia and stroke during chronic hypertension.

Animals↗
PubMed1990

Collateral development after carotid artery occlusion in Fischer 344 rats.

Mortality following permanent occlusion of both common carotid arteries decreases as the time between the first and second occlusions increases in Fischer 344 rats. Our goal was to examine the possibility that collaterals develop after unilateral carotid artery occlusion. During temporary occlusion of both carotid arteries in nine ketamine-anesthetized male rats, mean +/- SEM blood flow in both parietal cortices was 23 +/- 4% of the preocclusion (control) blood flow (120 +/- 7 ml/min/100 g) measured by laser Doppler flowmetry (p less than 0.05). After permanent occlusion of one carotid artery for either 1-2 days (n = 10) or 6 weeks (n = 7), mean +/- SEM blood flow was 16 +/- 2% and 30 +/- 3% of control, respectively, during a temporary test occlusion of the other carotid artery. During the test occlusion, blood flow in the cortex ipsilateral to the 6-week occlusion was 170% that in the contralateral cortex (which was similar to the blood flow immediately after temporary occlusion of both carotid arteries) and twice that after 1-2 days of occlusion. Mean luminal diameter of the basilar-carotid anastomosis ipsilateral to the 6-week occlusion was 186% that of the contralateral anastomosis, which showed only minimal change, and 145% that after 1-2 days of occlusion. We conclude that during 6 weeks of permanent carotid artery occlusion the anastomosis enlarges and its blood flow or reserve increases. Thus, collaterals developed ipsilateral to, but not contralateral to, the 6-week carotid artery occlusion, which suggests the possibility of greater collateral protection on the permanently occluded side.

Animals↗
PubMed1989

An assessment of proliferative and enzyme activity in transitional mucosa adjacent to colonic cancer.

The mucosa within 2 cm of cancers of the large bowel (transitional mucosa) shows histologic and histochemical changes which may indicate premalignant change. In this study, the authors used specimens from resected colonic tissue to compare morphometric, proliferative, and enzyme markers in transitional mucosa with those in cancer tissue and with those in uninvolved mucosa at least 10 cm from the cancer. Proliferative activity was assessed using the Ki 67 monoclonal antibody technique whereas a variety of methods were used to determine enzyme activities in mucosal homogenates. When compared to uninvolved mucosa, crypts in transitional mucosa contained greater number of cells, were significantly deeper and wider and were more likely to be branched. However, crypts in transitional mucosa had a significantly lower labelling index using the Ki 67 technique and there was no evidence of a shift in the proliferative zone towards the bowel lumen. The activities of ornithine decarboxylase, thymidine kinase, alkaline phosphatase, and lactate dehydrogenase were similar in transitional and uninvolved mucosa. Cancer tissue showed significantly higher levels of activity for ornithine decarboxylase and lactate dehydrogenase. Transitional mucosa showed morphometric changes but there were no proliferative or enzyme markers to suggest a higher than expected risk for malignant change.

Alkaline Phosphatase↗
PubMed1988

High NaCl predisposes Dahl rats to cerebral infarction after middle cerebral artery occlusion.

High (8%) and low (0.3%) NaCl diets were administered for 3 weeks before testing inbred Dahl salt-sensitive (SS/Jr) or salt-resistant rats (SR/Jr) for altered susceptibility to cerebral infarction after occlusion of the middle cerebral artery. At occlusion time, mean systolic blood pressure (BP) was 201 +/- 7 mm Hg in SS/Jr fed a high NaCl diet. Two weeks later an atrophied infarct was present in the territory of the occluded artery of all (n = 10) hypertensive SS/Jr, and infarct size was correlated with BP at occlusion time (p less than 0.01). In normotensive control SS/Jr fed a low NaCl diet (n = 11), BP (118 +/- 3 mm Hg), frequency of infarction (18%), and infarct size were all significantly less (p less than 0.05) than in the hypertensive rats. In SR/Jr fed a high (n = 11) or low (n = 10) NaCl diet, BP was not statistically different (112 +/- 4 vs 116 +/- 4 mm Hg). Cerebral infarction frequency was significantly (p less than 0.05) greater in SR/Jr fed a high NaCl diet (73%) than in SR/Jr receiving a low NaCl diet (20%), but infarct size was not correlated with BP in SR/Jr (p greater than 0.05). Thus, elevated NaCl intake in SS/Jr and SR/Jr before middle cerebral artery occlusion predisposes to cerebral infarction, but differences in infarct size and its correlation with BP suggest the controlling factors are not identical in the two strains.

Animals↗
PubMed1987

Dorsal cerebral collaterals of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY).

Earlier studies established that stroke-prone spontaneously hypertensive rats (SHRSP) invariably infarct after middle cerebral artery (MCA) occlusion. Normotensive rats are usually protected from infarction after the occlusion. Objectives of this study were to characterize the anastomosing collaterals that may determine the different outcomes to MCA occlusion in SHRSP and Wistar Kyoto rats (WKY). Young (5-10 week) and old (40-69 week) rats of each sex were anesthetized, then administered papaverine to produce maximal vasodilatation of the cerebrovascular bed. Under control conditions latex was injected into the arterial tree to measure the internal diameter of branches of the anterior cerebral artery (ACA), the MCA, and the ACA-MCA anastomosing collaterals. Large diameter ACA and MCA rami in old, but not young, SHRSP were significantly smaller in diameter than the respective ACA and MCA branches in old WKY. The number of ACA-MCA anastomoses was the same for SHRSP and WKY. Mean internal diameter of the ACA-MCA anastomoses was significantly (p less than 0.0001) smaller in SHRSP than WKY in both age groups. There were significant negative correlations between age and 1) the internal diameter of the ACA-MCA anastomoses in WKY but not SHRSP, and 2) the largest diameter ACA and MCA rami in SHRSP but not WKY. The findings suggest that vascular resistance of fully relaxed collaterals is greater in SHRSP than WKY, thereby compromising the dorsal collateral circulation before large diameter vessel changes occur that accompany the established form of hypertension.

Age Factors↗
PubMed1987

Differential uptake of 3H-thymidine by structures of the pia-arachnoid and cerebral cortex distal to the interrupted middle cerebral artery.

Tritiated thymidine accumulated in pial surface structures 1-10 days after interruption of the right middle cerebral artery (MCA) in the rat. Essentially no radioactive marker was present in the underlying cortical territory of the interrupted MCA other than at the operation site. Control meninges, cortex contralateral to the operated MCA, and structures proximal to the operation site were without appreciable accumulation of 3H-thymidine. Thus, the marked cellular proliferative response to MCA interruption was localized to structures of the pia-arachnoid overlying the cortical territory of the interrupted MCA. The data suggest that after MCA occlusion a cellular proliferative response contributes to the expansion of preexisting pial surface collateral vessels and that the expansion does not extend into the parenchyma.

Animals↗
PubMed1986

Limited proteolysis of IIIGlc, a regulatory protein of the phosphoenolpyruvate:glycose phosphotransferase system, by membrane-associated enzymes from Salmonella typhimurium and Escherichia coli.

In the present studies we report that membrane-associated proteases in Salmonella typhimurium and Escherichia coli catalyze limited proteolysis of IIIGlcSlow. We have previously reported (Meadow, N. D., and Roseman, S. (1982) J. Biol. Chem. 257, 14526-14537) the isolation of two electrophoretically distinguishable forms of IIIGlc, which is a phosphocarrier and regulatory protein of the phosphoenolpyruvate:glycose phosphotransferase system. The two species of IIIGlc were designated IIIGlcFast and IIIGlcSlow; IIIGlcSlow is 7 amino acid residues longer than IIIGlcFast at its NH2 terminus. The majority of the protease activity is located in the outer membrane fraction from both species of bacteria, with the cytoplasmic fraction being devoid of activity. The site of cleavage is at the Lys-Ser bond located at residues 7-8 of IIIGlcSlow. The enzyme is an endopeptidase which liberates the expected heptapeptide (Gly-Leu-Phe-Asp-Lys-Leu-Lys). Both the large fragment of the limited proteolytic reaction, IIIGlcFast, and the small fragment, the heptapeptide, are stable to further proteolysis by membranes for more than 17 h at 37 degrees C. The activity in E. coli membranes has an absolute requirement for divalent metal ion (Mg2+ or Ca2+) and is heat-resistant, whereas the activity in S. typhimurium membranes is stimulated by divalent metal ion and is heat-sensitive. These results suggest significant differences between the two enzymes. The physiological function of the limited proteolysis of IIIGlc is not known.

Cations, Divalent↗
PubMed1986

Structural brain correlates of emotional disorder in multiple sclerosis.

Eighty-seven patients with definite multiple sclerosis (MS) were examined neurologically and administered the Mini-mental State examination (MMS) to assess cognitive disability at the beginning and end of a one-year study. A CT scan was performed in 37. A group of 16 patients with stable spinal cord injuries (SCI) were studied in a similar manner. Of the MS patients, 47% had a mean General Health Questionnaire (GHQ) score in the abnormal range. This was a higher rate than in SCI patients (P = 0.004). Mean depression scores were similar in MS and SCI patients, but MS patients with brain involvement were more depressed than those with cord lesions only (P = 0.05). Depression score was unrelated to functional disability but was correlated with the degree of neurological impairment (P = 0.03). Euphoric patients were more likely to have brain involvement (P = 0.006), to have progressive MS (P less than 0.0001), and to have enlarged ventricles (P = 0.04) and were more impaired cognitively (P = 0.04) than noneuphoric patients. These results suggest that depression in MS patients is partly determined by the presence of brain involvement, but that it is also an emotional reaction to the disorder. Euphoria and cognitive disorder are reflections of brain involvement.

Adult↗
PubMed1986

Blood flow through cerebral collateral vessels in hypertensive and normotensive rats.

We tested the hypothesis that blood flow through cerebral collateral vessels is lower in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive Wistar-Kyoto rats (WKY) after occlusion of the middle cerebral artery and during maximal vasodilatation. Cerebral blood flow, measured with microspheres, was similar in adult male SHRSP and WKY under control conditions. In both strains, occlusion of the middle cerebral artery reduced blood flow and vascular conductance to the territory of the occluded artery, as compared with homologous tissue on the side contralateral to the occlusion. The territory distal to the site of occlusion was identified by intravital demarcation with neutral red dye. In both strains, vasodilatation produced by seizures after occlusion of the middle cerebral artery produced minimal increases in blood flow to the territory of the occluded artery. Blood flow and vascular conductance to the territory of the occluded MCA were significantly lower in SHRSP than in WKY (p less than 0.05) after occlusion and during seizure after occlusion. We conclude that after occlusion of the middle cerebral artery, there is less blood flow through cerebral collateral vessels in SHRSP than in WKY. We speculate that the lower blood flow through collateral vessels in SHRSP may be related to structural differences in those vessels. Thus, the tendency toward infarction after occlusion of the middle cerebral artery in SHRSP may be related, at least in part, to a more limited dilator reserve of cerebral collateral vessels in SHRSP.

Animals↗
PubMed1985

Interruption of the middle cerebral artery in 10-day-old rat alters normal development of distal collaterals.

Pial surface arterioles join rami of the anterior and middle cerebral arteries (MCA) in 10-day-old normal Wistar rats. Normally, the anastomosing branches differentiate into small-diameter vessels with significantly greater tortuosity (length) by 56 days of age. After interruption of th e MCA in 10-day-old rats, large-diameter, relatively straight collaterals were observed 46 or 90-110 days later. Evidently altered hemodynamic factors, as the result of MCA interruption, prevent the development of a normal pattern of arterioles and augment the development of an anomalous pattern of collaterals in young Wistar rats.

Age Factors↗