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Biomedical subjects

K C Hayes

Publications and source records attributed to K C Hayes.

At least 127 records · Page 7Linked to original sources

A fish oil diet retards experimental amyloidosis, modulates lymphocyte function, and decreases macrophage arachidonate metabolism in mice.

Several recent reports have shown that diets in which the only source of fat was fish oil can modify the course of diseases with an inflammatory or immune component. In these experiments we examined the effect of a fish oil diet on experimental amyloidosis in mice. In most azocasein-treated mice, amyloid deposits were found in the spleen, varying from a trace to wide and contiguous perifollicular bands. The spleens of mice receiving fish oil had significantly less amyloid than did spleens of mice fed corn oil. A marked increase in spontaneous blastogenesis that occurred in azocasein-treated mice on corn oil was suppressed in azocasein-treated mice on fish oil. Substitution of the unsaturated fatty acids of corn oil with those of fish oil was also found to modify the prostaglandin profile of macrophages. This altered profile may change cellular immune function and/or enhance the processing of serum amyloid A to retard the induction of secondary amyloidosis in mice.

Amyloidosis↗

Changes in short and long latency stretch reflexes prior to movement initiation.

The amplitudes of both short (M1) and long (M2) latency stretch reflexes mechanically elicited in the triceps brachii muscle were investigated prior to its voluntary activitation. The results obtained from 14 healthy subjects indicated that the amplitude of the M2 response increased steadily as the perturbation was delivered closer to the movement suggesting that the M2 changes are associated with the preparation to respond to the visual stimulus. In contrast, the amplitude of the M1 response showed no systematic variations over the same time period. This dissociation of the M1 and M2 reflex responses prior to movement may be attributable to selective gain modulation in supraspinal stretch reflex pathways or to descending projections to polysynaptic spinal pathways.

Adult↗

Taurine enhances low density lipoprotein binding. Internalization and degradation by cultured Hep G2 cells.

To evaluate the impact of taurine on hepatic cholesterol catabolism low density lipoprotein (LDL) binding, internalization and degradation were measured in cultured Hep G2 cells. Preincubation of cells with 0.1-10 mM taurine for 24 h stimulated LDL receptor activity by as much as 100%. Only the high affinity LDL receptor activity (specific) was increased by taurine preincubation, whereas the low affinity receptor activity (nonspecific) remained unchanged. Scatchard analysis of the binding data revealed that taurine doubled the number of LDL receptors without affecting receptor affinity. Taurine-enhanced LDL receptor activity was most pronounced when LDL concentrations exceeded 100 micrograms/ml, but was noted at taurine concentrations as low as 0.1 mM (plasma level). Interestingly, taurine had no effect on LDL receptor activity when it was added simultaneously with 125I-LDL to Hep G2 cells, or when non-bile acid-producing human skin fibroblasts were tested. Stimulation of LDL receptor activity was also obtained with 10 mM cysteine, a taurine precursor, but not with glycine. Increased cellular concentrations of taurine and cysteine were associated with an elevated rate of bile acid synthesis and a reduced cellular free cholesterol concentration. The data suggest that taurine enhanced LDL receptor activity by sparing cysteine, a known sulfhydryl group donor and stimulator of 7 alpha-hydroxylase activity, and that the latter stimulated bile acid production leading to increased utilization of cellular free cholesterol and enhanced LDL uptake.

Animals↗

Periodicity in the Hoffmann reflex recovery curve.

Hoffmann (H) reflex recovery curves were recorded from the soleus muscles of 10 healthy adult subjects with a view to further elucidating the pattern of facilitation of the motoneuron pool. Specific consideration was given to the possible existence of periodicity in facilitation of the motoneuron pool following a subthreshold conditioning H-reflex stimulus. The reliability of the recovery curves was also examined. The recovery curves, which utilized a 50% maximal test response, revealed the well established early facilitation (peak at 10 ms) followed by a later facilitation commencing 50 to 70 ms after the conditioning stimulus. In addition, there was evidence of peaks in excitability of the motoneuron pool occurring at 70 to 75 ms, 125 to 150 ms, and about 250 ms. The reliability of the periodicity in the recovery curve was established by examining the subjects on two separate occasions and investigating the effect of the number of measurements made within each day. Although there was considerable inter- and intrasubject variability in the form of the recovery curves, both within days, and between days, the overall group data showed a remarkably consistent periodicity for the first 350 ms following the conditioning stimulus. Methodological considerations that are important for observing the periodicity in the recovery curve were identified. These included an adequate number of measurements (test reflexes) per data point in the recovery curve, adequate sampling rate, and conditioning and test stimulus intensity. The clinical significance of these results resides in the possible contributions of the peripherally triggered periodic facilitation to rhythmic phenomena such as clonus and physiologic tremor.

Adult↗

Postural stability and Colles' fracture.

We have tested the hypothesis that the Colles' fracture is due, not simply to bone loss at the menopause, but to postural instability in a subset of postmenopausal women such that they are rendered more liable to fall. We have measured bone mass by dual photon spinal densitometry and single photon wrist densitometry and measured postural sway in 19 postmenopausal women with a history of Colles' fracture. Our results show that not only do Colles' fracture subjects have a small reduction in bone mass but they have a significantly increased degree of postural sway, a finding which has previously been recognized to characterize older subjects with recurrent falls.

Accidental Falls↗

Maturation of postural sway in young children.

The postural sway of 76 healthy young children aged from two to 14 years was investigated to identify age-related changes in the extent of sway, the effects of eye-closure, and the spectral composition of sway. Postural sway was measured from the excursions of the centre of pressure of ground reaction forces, and was analysed for both time and frequency. Within the age-range of the children tested, postural sway decreased linearly with age. Boys tended to become more stable at a faster rate than girls, but started from an initially greater level of instability. The children's Romberg quotients, which provide an index of the influence of eye-closure on sway magnitude, were remarkably low in comparison with adult values. Power spectral analysis of the postural sway showed that the principal energy was contained below 0.7 Hz for both lateral and antero-posterior sway, but that very young children had some power in the 0.8 to 2.0 Hz range. Taken together, these results confirm and extend the previously established view that children use visual information to control balance in a manner different from that of adults, and that it is not until after the age of seven years that adult-like balance-control strategies begin to appear. Also, in contrast to adults, the appearance of sway at high frequencies in children is not necessarily associated with any pathology.

Adolescent↗

Monocyte adherence to endothelial cells in vitro is increased by beta-VLDL.

The adherence of blood monocytes to the arterial endothelium is an early event in the development of atherosclerotic lesions. The possibility was investigated that alterations in the level and composition of plasma lipoproteins may contribute to this phenomenon. The adherence of human mononuclear cells to primary bovine aortic endothelial cells was measured in an in vitro monolayer collection assay. Preincubation of endothelial cells with beta-very low density lipoprotein (beta-VLDL) from cholesterol-fed rabbits or with very low density lipoprotein (VLDL) from cholesterol/saturated fat-fed cebus monkeys resulted in a significant increase in the subsequent adherence of monocytes to the endothelial cells. The effect of beta-VLDL was maximal at 100 micrograms protein/ml. The response increased with time when endothelial cells were incubated with beta-VLDL for 0-120 minutes, then remained maximal for up to 4 hours. The adherence of a human monocytic cell line (U937) to endothelial cells was also increased by beta-VLDL. These results suggest that diet-induced alterations in lipoprotein composition may contribute to the development of atherosclerotic lesions by affecting the adherence of monocytes to the arterial endothelium.

Animals↗

The apo E/apo CIII molar ratio affects removal of cholesterol ester from modified human lipoproteins injected into cebus monkeys.

The removal of postprandial (PP) and postabsorptive (PA) human LDL and HDL cholesterol was examined in cebus monkeys (Cebus albifrons) following in vitro labelling of these lipoproteins by 3H-cholesterol in the presence or absence of DTNB. The removal of LDL cholesteryl ester was 3.5 and 2 times greater than that of HDL in male and female monkeys, respectively. Incubation with DTNB reduced cholesteryl ester removal by 45 and 52% for LDL and HDL, respectively. Cholesteryl ester from PA lipoproteins was removed 80% faster than that PP particles only when plasma was incubated without DTNB. Cholesterol removal from these lipoproteins was positively (r = 0.941) and significantly (P less than 0.001) correlated with the molar apo E/apo CIII ratio. The data suggest that density of lipoproteins was less important than their apoprotein composition in dictating their removal from circulation.

Absorption↗

Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice.

The potential for vitamin E to modulate prostaglandin metabolism and alter immune response in aged mice was studied. Semi-purified diets containing 30 ppm or 500 ppm dl-alpha-tocopheryl acetate (VitE) were fed for 6 weeks to young (3 months) and old (24 months) C57BL/6J mice. Delayed hypersensitivity skin test to DNFB and the proliferative response of splenocytes to T- and B-cell mitogens were assessed. Ex-vivo synthesis of Prostaglandin E2 (PGE2) was measured in spleen homogenates and serum vitamin E was measured by HPLC. Vitamin E supplementation of aged mice enhanced percent ear swelling to DNFB as well as the mitogenic response of splenocytes to Con A and LPS (P less than 0.05). Furthermore, spleen homogenates from old mice fed 30 ppm VitE had a significantly higher PGE2 level than young mice fed 30 ppm VitE and old mice fed 500 ppm VitE (3.20 +/- 0.07 micrograms/g vs. 2.60 +/- 0.08 and 2.3 +/- 0.10, respectively). Thus, the vitamin E enhanced immune response of aged mice appears to be mediated by decreased prostaglandin synthesis.

Aging↗

Comparative assessment of soy and milk protein quality in infant cebus monkeys.

Protein qualities of lactalbumin (L), casein (C), soy concentrate (SC), soy isolate (SI), and soy isolate plus 15.3 mg methionine/g protein (SIM) were investigated in a slope-ratio assay using 32, 8-wk old cebus monkeys. Growth (28 days) and nitrogen balance (NB) (days 19-28) data were evaluated in a multiple-regression format with nitrogen intake and body weight as the independent variables. Based upon growth, potencies compared to L were: C, 72.1; SC, 52.5; SI, 40.6; and SIM, 72.2. Based upon NB, comparable potencies were: C, 62.2; SC, 69.0; SI, 46.8; and SIM, 90.7. NB data showed that the potency of SC was significantly greater than SI and that methionine supplementation of SI improved it to a potency not distinguishable from the standard. The marked improvement from SI to SIM emphasizes the beneficial effect of sulfur amino acid supplementation of soy protein for an infant primate species.

Animals↗

ApoE distribution among lipoproteins of rhesus monkeys is modulated by dietary fat and cholesterol.

The effect of dietary saturated fat and cholesterol on plasma cholesterol and apolipoprotein E (apoE) distribution among lipoproteins was studied in rhesus monkeys. Two groups of four monkeys had been fed diets containing 31% energy as either corn oil or coconut oil for 5 yr from birth. Each group was then fed short-term their respective diet with a 0.2% cholesterol supplement, the opposite fat without cholesterol, the opposite fat +0.2% cholesterol, followed by their original fat without cholesterol for 5 to 8 wk periods. Plasma was assayed for total cholesterol, total triglyclerides, and the distribution of apoE within lipoproteins (VLDL, IDL, LDL, HDL) separated by gradient-density electrophoresis. When coconut oil was fed, plasma cholesterol and triglyceride concentrations were 134% and 157%, respectively, of the levels when corn oil was fed. Cholesterol supplementation of corn oil also elevated the plasma cholesterol (141%), whereas cholesterol supplementation of coconut oil appeared to induce a synergistic increase (198%). Both groups of monkeys responded similarly to a given diet. The distribution of apoE in lipoproteins differed according to dietary treatment, with cholesterol feeding causing a major shift from HDL to IDL, whereas coconut oil caused a modest shift from HDL to VLDL. The relative amount of apoE in LDL was unchanged by diet. We conclude that dietary saturated fat or cholesterol can modulate the apoE distribution within lipoproteins in rhesus monkeys in conjunction with the previously noted expansion of the cholesteryl ester pool in VLDL and IDL.

Animals↗

LDL enhances monocyte adhesion to endothelial cells in vitro.

Monocyte adhesion to the arterial endothelium is an early event in diet-induced atherogenesis. The possibility that low-density lipoprotein (LDL) may influence this adhesion was investigated by using an in vitro monolayer collection assay. Postprandial and fasting LDL was isolated from 12 normal adult human donors (8 male and 4 female) and incubated with primary cultures of bovine aortic endothelial cells (BAEC) for 6 hours. 51Cr-labeled mononuclear leukocytes (MNLs) were then added and incubated an additional 30 minutes. When results were expressed as the ratio of adherent counts per minute in LDL-treated BAEC cultures to that in PBS-treated controls, 10 of the 16 LDL samples isolated from male donors induced a significant increase (P less than 0.05) in MNL adhesion (1.06-1.27) attributable to esterase-positive cells. This increase was dose-dependent and maximal at 100 micrograms LDL protein/ml. The magnitude of the response was significantly correlated with LDL composition (r = 0.857, P less than 0.01) such that LDL rich in cholesterol and triglyceride relative to protein enhanced MNL adhesion, whereas lipid-poor LDL (typically isolated from the women) reduced adhesion.

Animals↗

How many strides are required for the analysis of electromyographic data in gait?

This study was conducted to obtain information on the number of strides of EMG data needed per subject in a gait study. Ten strides of EMG data were cumulated on eight subjects for each of the soleus, rectus femoris, biceps femoris, vastus medialis and tibialis anterior muscles. The linear envelope of the EMG, normalized in time and amplitude, demonstrated a very high level of stability for a given subject, relative to the variability that was found across subjects. It was concluded that three strides of EMG data per subject provides information as reliable as that obtained from twelve strides.

Adult↗

Experimental arthritis in a nonhuman primate. I. Induction by bovine type II collagen.

Six squirrel monkeys immunized with native fetal bovine type II collagen (CII) in complete Freund's adjuvant developed arthritis 3 to 6 weeks later. None of three cebus monkeys given CII plus complete Freund's adjuvant or three control squirrel monkeys immunized with complete Freund's adjuvant alone developed arthritis. In four of the squirrel monkeys, arthritis was symmetrical and involved mainly the interphalangeal and metacarpal phalangeal joints. Two other monkeys had pauciarticular disease. Although three monkeys became cachetic and died, the others regained weight and their arthritis spontaneously remitted with minor residual deformities in digits and larger joints. Each squirrel monkey with arthritis had high titers of CII antibodies whereas the arthritis-resistant cebus monkeys had lower titers of CII antibodies whereas the arthritis-resistant cebus monkeys had lower titers of CII antibodies. As an animal model, experimentally induced arthritis in primates appears to resemble an acute arthropathy in man rather than chronic rheumatoid arthritis.

Acute Disease↗

Dietary fish oil modulates macrophage fatty acids and decreases arthritis susceptibility in mice.

B10.RIII and B10.G mice were transferred from a diet of laboratory rodent chow to a standard diet in which all the fat (5% by weight) was supplied as either fish oil (17% eicosapentaenoic acid [EPA], 12% docosahexaenoic acid [DHA], 0% arachidonic acid [AA], and 2% linoleic acid) or corn oil (0% EPA, 0% DHA, 0% AA, and 65% linoleic acid). The fatty acid composition of the macrophage phospholipids from mice on the chow diet was similar to that of mice on a corn oil diet. Mice fed the fish oil diet for only 1 wk showed substantial increases in macrophage phospholipid levels of the omega-3 fatty acids (of total fatty acid 4% was EPA, 10% docosapentaenoic acid [DPA], and 10% DHA), and decreases in omega-6 fatty acids (12% was AA, 2% docosatetraenoic acid [DTA], and 4% linoleic acid) compared to corn oil-fed mice (0% EPA, 0% DPA, 6% DHA, 20% AA, 9% DTA, and 8% linoleic acid). After 5 wk this difference between the fish oil-fed and corn oil-fed mice was even more pronounced. Further small changes occurred at 5-9 wk. We studied the prostaglandin (PG) and thromboxane (TX) profile of macrophages prepared from mice fed the two diets just before being immunized with collagen. Irrespective of diet, macrophages prepared from female mice and incubated for 24 h had significantly more PG and TX in the medium than similarly prepared macrophages from male mice. The increased percentage of EPA and decreased percentage of AA in the phospholipids of the macrophages prepared from the fish oil-fed mice was reflected in a reduction in the amount of PGE2 and PGI2 in the medium relative to identically incubated macrophages prepared from corn oil-fed mice. When this same fish oil diet was fed to B10.RIII mice for 26 d before immunization with type II collagen, the time of onset of arthritis was increased, and the incidence and severity of arthritis was reduced compared to arthritis induced in corn oil-fed mice. The females, especially those on the fish oil diet, tended to have less arthritis than the males. These alterations in the fatty acid pool available for PG and leukotriene synthesis suggest a pivotal role for the macrophage and PG in the immune and/or inflammatory response to type II collagen.

Animals↗

Evidence for distinct precursor pools for biliary cholesterol and primary bile acids in cebus and cynomolgus monkeys.

The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones. To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein free 14C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid pool washout, monkeys were infused with human LDL or HDL labeled with free 14C-cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA.

Animals↗

Dietary fat unsaturation enhances drug metabolism in cebus but not in squirrel monkeys.

Antipyrine disappearance and sleeping time following barbiturate anesthesia were assessed to evaluate the effects of dietary corn oil and coconut oil on the drug-metabolizing enzyme systems (DMES) in cebus (Cebus albifrons) and squirrel (Saimiri sciureus) monkeys. Plasma antipyrine clearance (half-life) was measured in both species before and after induction of DMES by i.v. injection of barbiturates on two consecutive days. Sleeping time was measured after administration of either pentobarbital or hexobarbital and proved to be the most demonstrable measure of diet-drug interaction. In neither cebus nor squirrel monkeys was antipyrine half-life significantly affected by dietary fat. Sleeping time for the coconut oil-fed squirrel monkeys was shorter than for those fed corn oil, whereas corn oil-fed cebus awoke sooner than the coconut oil-fed cebus. Thus, barbiturate but not antipyrine metabolism in monkeys can be influenced by dietary fat unsaturation, and the effect appears to be species dependent. Genetic differences in phospholipid metabolism are thought to underlie this difference.

Animals↗