PubMed Health⌕ Search

Biomedical subjects

R J Morin

Publications and source records attributed to R J Morin.

At least 19 recordsLinked to original sources
PubMed2001

Inconsistent link between low-frequency oscillations: R-R interval responses to augmented Mayer waves.

Low-frequency oscillations in arterial blood pressure (Mayer waves) and R-R interval are thought to be linked through the arterial baroreflex. To delve into this relationship, we applied low (10 mmHg) and moderate (30 mmHg) lower body negative pressure (LBNP) in 10-s cycles to 18 healthy young male subjects. They showed no change in average blood pressure with this oscillatory stimulus but did show a significant decrease in R-R interval (P < 0.05) during both levels of LBNP. In addition, we succeeded in augmenting low-frequency blood pressure oscillations in a graded response to oscillatory LBNP level (P < 0.05) while significantly increasing low-frequency R-R interval oscillations (P < 0.05). However, cross-spectral coherence between these increased oscillations was highly variable across individuals and stimulus level. Although nearly all subjects showed significant coherence during basal conditions (n = 17), only seven subjects maintained significant coherence during both levels of LBNP. These results suggest that a complex interaction of regulatory mechanisms determines the link between low-frequency oscillations and the responses to even low levels of LBNP.

Adult↗
PubMed1999

Effects of age and gender on autonomic control of blood pressure dynamics.

Both age and gender influence cardiovascular autonomic control, which in turn may influence the ability to withstand adverse cardiac events and respond to orthostatic stress. The purpose of this study was (1) to quantify age- and gender- related alterations in autonomic control of blood pressure (BP) and (2) to examine the impact of these autonomic alterations on BP response to orthostatic stress. We measured continuous BP and R-R intervals and vasoactive peptide levels in the supine and 60 degrees head-up tilt positions during paced respiration (0.25 Hz) in 89 carefully screened healthy subjects (41 men, 48 women, aged 20 to 83 years). Data were analyzed by gender (age adjusted) and by age group (gender adjusted). During tilt, women had greater decreases in systolic BP than men (-10.2+/-2 versus -1.2+/-3 mm Hg; P=0.02) and smaller increases in low-frequency (sympathetically mediated) BP power (P=0.02). Upright plasma norepinephrine was lower in women (P=0.02). Women had greater supine high-frequency R-R interval power than men (P=0.0001). In elderly subjects, the tilt-induced increase in low-frequency BP power was also diminished (P=0.01), despite higher supine (P=0.02) and similar upright norepinephrine levels compared with younger subjects. Thus, healthy women have less sympathetic influence on BP and greater parasympathetic influence on R-R interval than men. Elderly subjects also have reduced sympathetic influence on BP, but this appears to be more consistent with a reduction in vasomotor sympathetic responsiveness.

Adult↗
PubMed1998

Complex demodulation of cardiorespiratory dynamics preceding vasovagal syncope.

BACKGROUND: The dynamic autonomic processes leading to vasovagal syncope are poorly understood. METHODS AND RESULTS: We used complex demodulation to continuously assess changes in respiration, R-R interval, and arterial pressure (blood pressure) variability during 60 degree head-up tilt in 25 healthy subjects with tilt-induced vasovagal syncope and 25 age-matched nonsyncopal control subjects. Coherence and transfer function analyses were used to examine the relation between respiration and R-R interval variability before syncope. Baseline blood pressure, R-R, and ventilation were similar between syncope subjects and control subjects. Syncope subjects experienced an increase in tidal volume and decrease in BP beginning 3 minutes before impending syncope (systolic blood pressure <80 mm Hg) necessitated termination of tilt. Approximately 90 seconds before syncope there was a sudden prolongation of R-R interval and increase in amplitude of high and low frequency R-R interval variability, indicating an abrupt enhancement of vagal tone. The increase in respiratory amplitude between 180 and 90 seconds before syncope was not accompanied by changes in R-R interval or R-R variability, suggesting a dissociation between respiration and the respiratory sinus arrhythmia. The coherence analysis showed fewer syncope subjects with coherence between respiratory and R-R interval variabilities and lower transfer magnitudes in syncope subjects compared with control subjects. Nonsyncopal subjects had no change in respiratory, R-R interval, or blood pressure dynamics during matched time periods before the time of syncope. CONCLUSIONS: Vasovagal syncope is preceded by a period of hyperpnea and cardiorespiratory decoupling followed by an abrupt increase in cardiovagal tone. Respiratory pumping without inspiratory cardiac slowing may partially counteract preload reduction until sudden bradycardia precipitates syncope.

Adult↗
PubMed1997

Preliminary evidence for the evolution in complexity of heart rate dynamics during autonomic maturation in neonatal swine.

Previous studies suggest that the autonomic nervous system plays an important role in the generation of complex heart rate dynamics. Therefore, we hypothesized that the complexity (irregularity) of cardiac interbeat intervals would evolve with the maturation of autonomic innervation to the heart. Twelve healthy newborn piglets were implanted with ECG transmitters and studied at one or more different ages up to 33 days of age, the period during which pigs develop functional sympathetic innervation of the heart from the stellate ganglia. Three animals underwent right stellate ganglionectomy, two a left stellate ganglionectomy, two a right cardiac vagotomy and five a sham procedure. The statistic, approximate entropy (ApEn), was used to quantify the regularity of interbeat interval fluctuations. Sham-operated animals showed an increase in the standard deviation (SD) and irregularity (ApEn) of cardiac interval fluctuations with increasing age. Right stellate ganglionectomized piglets had lower interbeat interval ApEn values, but similar SD's by 26-27 days of age compared to sham-operated animals. Left stellate ganglionectomy, which affects cardiac inotropy rather than chronotropy, had no effect on cardiac interval irregularity, while vagotomy had an indeterminant effect. The increasing irregularity of interbeat interval dynamics during autonomic maturation and the apparent attenuation of heartbeat irregularity when right stellate ganglion innervation is interrupted, provides empirical support for the notion that complex heartbeat dynamics in the mature animal are the result of a network of autonomic neural pathways that enables an organism to adapt to stress.

Aging↗
PubMed1996

Lip cancer: a review.

Dental examinations should routinely include examination of the lips by visual inspection and palpation. The primary risk factor for lip cancer is actinic damage. Squamous cell carcinoma of the lip accounts for about nine per cent of all oral cancers, but there has been a downward trend in the number of cases reported from 1973 to 1984. This trend may be due to the increased use of sunscreens. The clinical presentation and management of lip cancer are discussed.

Carcinoma, Squamous Cell↗
PubMed1996

Inhibitory effect of cholesterol oxides on low density lipoprotein receptor gene expression.

The effects of the cholesterol oxides on low density lipoprotein receptor (LDLR) gene expression were investigated. Cultured rabbit aortic smooth muscle cells were incubated with 1, 2, and 5 micrograms/ml culture medium concentrations of pure cholesterol, 25-hydroxycholesterol (25-OH), 7-ketocholesterol (7-keto), cholestane-3 beta, 5 alpha, 6 beta-triol (triol) and cholesterol-5 alpha, 6 alpha-epoxide (epoxide) for 12 hours and with vehicle only as control. Total mRNAs were extracted and electrophoresed. Northern blot hybridization analyses were performed. The results showed mRNA expressions of LDLR gene were inhibited to 16.1 +/- 4.4%, 33.8 +/- 0.6%, 42.8 +/- 1.8% and 46.9 +/- 3.9% of control by 25-OH, 7-keto, epoxide and triol respectively. Pure cholesterol showed only minimal inhibition. The inhibitions were time dependent. Although cholesterol oxides have been shown to alter many membrane-related functions and the LDLR domain are located in the cell membrane. The findings of this study suggested that the cholesterol oxides exerted their repressive actions on LDLR function primarily by down-regulating LDLR gene expression rather than directly upon cell membrane.

Animals↗
PubMed1995

CYP-2E1 inhibitors partially ameliorate the changes in hepatic fatty acid composition induced in rats by chronic administration of ethanol and a high fat diet.

The objective of this study was to determine if ethanol-induced cytochrome P450 2E1 (CYP2E1) was responsible for the changes in hepatic fatty acids observed in rats fed ethanol intragastrically. We hypothesized that if CYP2E1 was responsible for these changes then CYP2E1 inhibitors fed with ethanol should prevent the ethanol-induced changes in fatty acids. We compared the fatty acid composition of the liver in rats fed ethanol alone with that in rats fed ethanol with the CYP2E1 inhibitors, diallyl sulfide and phenethyl isothiocyanate. In each experiment, rats pair-fed isocaloric glucose were included to determine the effect of the inhibitors alone on the hepatic fatty acid composition. The lobular distribution of succinic dehydrogenase was determined histochemically because the lobular distribution of CYP2E1 shifts to the periportal area in livers of rats fed CYP2E1 inhibitors. The CYP2E1 inhibitors ameliorated both the ethanol-induced changes in fatty acids and the shift in succinic dehydrogenase. Rats fed ethanol but no inhibitors had significantly greater hepatic total fatty acids and triglyceride fractions than when inhibitors were fed ethanol. Ethanol altered the fatty acid composition compared with rats fed ethanol with CYP2E1 inhibitors. The ratio of 20:4/18:2 was significantly lower and that of 18:1/18:0 was greater in alcohol-fed rats compared with their pair-fed controls. The CYP2E1 inhibitors inhibited many of the above effects of alcohol. The data suggest that the changes in the fatty acid composition due to ethanol ingestion are the result of CYP2E1-dependent lipid peroxidation and fatty acid metabolism.

Allyl Compounds↗
PubMed1995

Effects of chronic estrogen replacement therapy on beat-to-beat blood pressure dynamics in healthy postmenopausal women.

Recent data showing gender differences in autonomic control of heart rate and acute estrogen effects on vasodilatation suggest that estrogen may influence autonomic regulation of heart rate and blood pressure. We aimed to determine the effect of postmenopausal estrogen replacement therapy on autonomic control of beat-to-beat heart rate and blood pressure dynamics. Subjects included 20 healthy postmenopausal women aged 60 to 75 years with normal exercise tolerance tests, 10 of whom were taking oral estrogen for 13 +/- 3 (+/- SEM) years. Six healthy premenopausal women were also studied. Continuous electrocardiographic and noninvasive radial artery blood pressure measurements and intermittent forearm blood flow recordings (by venous-occlusion plethysmography) were obtained before and after a 20-minute, 60 degrees head-up tilt and a 420-kcal meal during periods of spontaneous and metronomic breathing (at 0.25 Hz). Low-frequency (0.01- to 0.15-Hz) and high-frequency (0.15- to 0.50-Hz) heart rate and blood pressure spectral powers were compared with a fast Fourier transform. Cardiovascular and heart rate spectral power responses to upright tilt and meal digestion were the same in postmenopausal estrogen users and nonusers. However, during spontaneous breathing the blood pressure spectral power responses to upright tilt and meal ingestion were significantly different between the two groups of women. The low-frequency systolic pressure power response to upright tilt was smaller in estrogen users than nonusers (P = .01). After meal ingestion nonusers had an early postprandial fall (20 to 30 minutes after the meal) and late rise (50 to 60 minutes) in low-frequency systolic and diastolic pressure powers, which were significantly attenuated in estrogen users (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Effect of cholesterol oxides on prostacyclin production and platelet adhesion.

Prostacyclin (PGI2) is synthesized primarily by endothelial cells, is essential for maintenance of vascular integrity, and may play a role in atherogenesis. Human umbilical vein endothelial cells in culture were incubated with either pure cholesterol, 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha,6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol at 10 micrograms/ml culture medium concentration for 12 hours and 24 hours. PGI2 production measured by radioimmunoassay of 6-keto PGF1 alpha, the stable metabolite of PGI2 was inhibited by 39.6%, 27.3%, 40.1% and 31.9% after incubation with 25-hydroxycholesterol, 7-ketocholesterol, cholesterol 5 alpha, 6 alpha-epoxide or cholestane-3 beta,5 alpha,6 beta-triol for 12 hours respectively. Further inhibitory effects were shown after 24 hours of incubation with 25-hydroxycholesterol and 7-ketocholesterol. Platelet adhesion onto endothelial cell monolayers measured by 111In-labeled platelets was enhanced by 104%, 54% and 37% after incubation with cholestane-3 beta, 5 alpha,6 beta-triol, 25-hydroxycholesterol, and 7-ketocholesterol at 10 micrograms/ml concentration for 12 hours respectively. Pure cholesterol at the same concentration had no effect on PGI2 production or platelet adhesion.

Arteriosclerosis↗
PubMed1991

Angiotoxicity and atherogenicity of cholesterol oxides.

Cholesterol in the diet can readily autoxidize and be absorbed and transported in plasma lipoproteins. Cholesterol oxides can also be endogenously produced in tissues via free-radical-induced reactions. Some cholesterol oxides, notably cholestane-3 beta, 5 alpha, 6 beta-triol and 25-hydroxycholesterol, have been shown to cause injury to vascular endothelial and smooth muscle cells, to alter LDL receptor function, to enhance cholesteryl ester accumulation, to inhibit prostacyclin production, and to induce experimental atherosclerosis alone or in combination with cholesterol. An epidemiological study examining relationships between atherosclerosis and plasma levels of cholesterol oxides as independent risk factors may provide additional insights regarding the roles of cholesterol oxides in atherogenesis.

Animals↗
PubMed1991

Cholesterol oxides and carcinogenesis.

Experimental evidence indicates a relationship between cholesterol alpha-epoxide and skin cancer, and exposure of skin fibroblasts to ultraviolet radiation enduces formation of significant levels of this oxide. Colon cancer is also etiologically linked to cholesterol oxidation products. Higher than normal levels of cholestanetriol have been found in patients with colon cancer and also in those with precancerous disorders such as adenomatous polyps and ulcerative colitis. Higher than normal levels of cholesterol alpha-epoxide have been found in breast fluid aspirates of women with benign breast disease, with or without atypical hyperplasia of the epithelium, and this may be a factor in the increased incidence of breast cancer associated with hyperplasia. Similarly, the observed increased levels of cholesterol alpha and beta-epoxides in prostatic fluid of men with benign prostatic hypertrophy may be associated with subsequent development of prostate cancer. Cholesterol alpha-epoxide has been found to be mutagenic to fibroblasts in culture and to induce morphological transformation in hamster embryo cells and in mouse C3H cells. 25-Hydroxycholesterol and 20 alpha-hydroxycholesterol are potent suppressors of generation and proliferation of tumor-specific cytotoxic T lymphocytes. Although investigations into the role of cholesterol oxidation products in cancer are still in the early stages, evidence to date indicates a potentially significant role in the induction of some types of cancer.

Animals↗
PubMed1991

Effects of cholestanetriol on cytotoxicity and prostacyclin production in cultured rabbit aortic endothelial cells.

Rabbit aortic endothelial cells in culture were incubated with 10 micrograms/ml of either pure cholesterol or cholestane-3 beta, 5 alpha, 6 beta-triol (triol) for 12 or 24 hours. Cells incubated with triol showed an increased rate of cell death, decreased [3H]-thymidine incorporation and decreased prostacyclin production as compared to either the control or the pure cholesterol group. These effects were more marked at 24 hours than at 12 hours. Pure cholesterol had no significant effects on any of the above parameters at either time interval. These results suggest potential atherogenic mechanisms for cholestanetriol, one of the most biologically active cholesterol oxidation products.

Animals↗
PubMed1989

Relative specificities of inhibition of acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase in cultured rabbit aortic smooth muscle cells by esterastin and cholesteryl oleyl ether.

Rabbit aortic smooth muscle cells in culture were incubated with 0.04-500 M esterastin. Acid cholesteryl ester hydrolase (ACEH) and neutral cholesteryl ester hydrolase (NCEH) activities were inhibited to a comparable degree, with 50% inhibition occurring in the range of 0.4 M esterastin. Cells incubated with cholesteryl oleyl ether showed 50% inhibition of NCEH at 5.0 M, but no inhibition of ACEH over a concentration range of 0.2-20 M. This relative specificity of cholesteryl oleyl ether for NCEH can be employed to study the relative roles of ACEH vs. NCEH in preventing cellular cholesteryl ester accumulation.

Animals↗
PubMed1989

Effects of cholesterol oxidation derivatives on cholesterol esterifying and cholesteryl ester hydrolytic enzyme activity of cultured rabbit aortic smooth muscle cells.

The effects of 5 micrograms/ml of 25-hydroxycholesterol; cholestane-3 beta,5 alpha,6 beta-triol; and cholesterol on acyl CoA cholesterol acyltransferase, acid cholesteryl ester hydrolase and neutral cholesteryl ester hydrolase was studied in cultured rabbit aortic smooth muscle cells. After 1 hour incubation, 25-hydroxycholesterol resulted in a fourfold stimulation of acyl CoA cholesterol acyltransferase activity. No stimulation by 25-hydroxycholesterol was noted before 15 minutes or after 5 hours of incubation. Neither cholestane-3 beta,5 alpha,6 beta-triol nor cholesterol influenced acyl CoA cholesterol acyltransferase activity at any time interval. No significant effects of any of the sterols were noted on acid cholesteryl ester hydrolase or neutral cholesteryl ester hydrolase activity. The imbalance between acyl CoA cholesterol acyl transferase and hydrolase activities induced by 25-hydroxycholesterol could result in cholesteryl ester accumulation by arterial smooth muscle cells, which may be associated with atherosclerosis.

Animals↗
PubMed1987

Transport of cholesterol autoxidation products in rabbit lipoproteins.

Radiolabeled pure [4-14C]cholesterol was kept at 60 degrees C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24, and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractionated by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3 beta,5 alpha,6 beta-triol, 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products.

Absorption↗
PubMed1987

Effects on membrane function by cholesterol oxidation derivatives in cultured aortic smooth muscle cells.

Autoxidation derivatives of cholesterol known to affect cholesterol content of the cells were shown to alter some membrane associated functions in cultured aortic smooth muscle cells. For study of membrane-bound enzymes, Na+,K+-ATPase and 5'-nucleotidase were measured cytochemically by electron microscopy. Cells incubated with 10 ug/ml of cholestane-3 beta,5 alpha,6 beta-triol and 25-hydroxycholesterol for 24 to 48 hours showed marked inhibition of both enzyme activities. For study of carrier-mediated hexose transport, radiolabeled 2-deoxy-D-glucose was utilized. The uptake of this labeled compound was measured in the cells preincubated with oxidation derivatives of cholesterol for various time periods. Cholestane-3 beta,5 alpha,6 beta-triol had a rapid inhibitory effect on hexose transport, which was reversible after removal of the sterol from the medium. Hexose transport was not significantly altered by 25-hydroxycholesterol after up to 8 hours incubation. Two underlying mechanisms are possible. The prompt onset of the effect of cholestane-3 beta,5 alpha,6 beta-triol may be attributable to an incorporation of the sterol into the cell membranes. On the other hand, 25-hydroxycholesterol, a potent inhibitor of cholesterol biosynthesis, may have a delayed effect on membrane function by depleting the cholesterol available for membrane synthesis.

5'-Nucleotidase↗
PubMed1985

Cholesterol oxidation derivatives and arterial endothelial damage.

Three groups of New Zealand male while rabbits were given either 2.5 mg/kg of 25-hydroxycholesterol, cholestane-3 beta, 5 alpha, 6 beta-triol or vehicle only, intravenously. 24 h after treatment, the luminal surfaces of aortae of rabbits receiving 25-hydroxycholesterol were examined by scanning electron microscopy (SEM) and showed numerous balloon-like protrusions and crater-like defects as well as circulating, formed elements adhering on the luminal surface. The luminal surface of aortae of rabbits given cholestane-3 beta, 5 alpha, 6 beta-triol had similar but more frequent lesions when compared with those of the 25-hydroxycholesterol group. Microthrombi were occasionally found. The aortae of the control group had significantly fewer lesions. Transmission electron-microscopic studies showed intracytoplasmic vacuoles and diffuse subendothelial edema in the aortae of the two groups receiving the oxidation derivatives of cholesterol. The balloon-like protrusions and crater-like defects observed by SEM appeared to represent the initial sterol-induced endothelial cell injury. Repeated episodes of arterial injury followed by thrombus formation could eventually lead to atherosclerosis.

Animals↗