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Biomedical subjects

T Billington

Publications and source records attributed to T Billington.

At least 19 recordsLinked to original sources
PubMed1998

Stomatal guard cell responses to kinetin and natriuretic peptides are cGMP-dependent.

Immunological evidence suggest that plants contain natriuretic peptides (NPs) and furthermore (3-[I]iodotyrosol) rat atrial NP (rANP) binds specifically to plant membranes. rANP and immunoaffinity-purified plant NP analogues also promote concentration-dependent stomatal opening. Here we report that kinetin, a synthetic cytokinin, and rANP induce stomatal opening in Tradescantia albiflora and that the effect of rANP is critically dependent on the secondary structure of the peptide hormone. The native circular molecule is active, whereas the linearized molecule shows no biological activity. Furthermore, kinetin- and rANP-induced stomatal opening is reversibly inhibited by two inhibitors of guanylate cyclase, LY 83583 and methylene blue. Stomatal opening is also induced in a concentration-dependent manner by the cell-permeant cyclic guanosine-3',5'-monophosphate (cGMP) analogue 8-Br-cGMP, and this effect is prevented by the stomatal closure promoting plant hormone abscisic acid (ABA). We conclude that in guard cells kinetin and rANP pathways operate via guanylate cyclase upregulation, and we propose that ABA-induced closure is not cGMP-dependent.

Adenine↗
PubMed1997

Isolation and immunoaffinity purification of biologically active plant natriuretic peptide.

It has recently been demonstrated that antibodies against atrial natriuretic peptides (ANP) recognise analogues in plants and that rat ANP binds specifically to isolated plant membranes and promotes stomatal guard cell opening in a concentration dependent manner. Here we report the isolation and immunoaffinity purification of plant natriuretic peptide (PNP) from ivy (Hedera helix) with rabbit anti-alpha-ANP (1-28) (human, canine) antiserum. We also demonstrate that immunoaffinity purified plant peptide induces stomatal opening in a concentration dependent manner. This is therefore the first report of an active indigenous peptide hormone in plants. We propose that PNPs are part of a signalling system that has evolved early in evolution and is involved in the regulation of ion transport and transpiration in plants.

Animals↗
PubMed1995

Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice.

Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, in mice, the role of LIF in septic shock. During sublethal endotoxemia, serum LIF levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas in lethal Escherichia coli septic shock serum LIF levels rose progressively (> 30 ng/ml) in the premorbid phase coincident with the development of tissue injury. Single i.v. injections of high doses (up to 50 micrograms per mouse) of recombinant murine LIF had no obvious acute detrimental effects, whereas continued i.p. administration (30 micrograms per mouse per day) for 3-4 days induced a fatal catabolic state without evidence of preceding hemodynamic collapse or shock. Simultaneous or subsequent administration of high doses of LIF had no effect on mortality from sublethal and lethal E. coli septic shock, whereas prior administration conferred significant protection against lethality (P << 0.001 by log-rank test), an effect that was dose and interval dependent. This protective effect resembled endotoxin tolerance and was characterized by suppression of E. coli-induced serum tumor necrosis factor concentration (P < 0.05), reduction in the number of viable bacteria (P < 0.05), and prevention of sepsis-induced tissue injury. These observations suggest that systemic LIF production is part of the host response to both endotoxin and sepsis-induced tissue injury.

Animals↗
PubMed1989

Lipids and lipoproteins in patients undergoing coronary-artery surgery.

Fasting blood samples were obtained from 290 patients who were undergoing elective coronary-artery graft procedures, and cholesterol, triglyceride and high-density lipoprotein cholesterol levels were measured. The 1983 National Heart Foundation of Australia's Risk Factor Prevalence Study was used as a source of age- and sex-matched "control" data. Of these patients, 80% had cholesterol levels of greater than 5.5 mmol/L; in 55% of patients, the level exceeded 6.5 mmol/L. Only 4% of patients who received a graft showed hypertriglyceridaemia alone (triglyceride level, greater than 2 mmol/L). Combined hyperlipidaemia (cholesterol level, greater than 5.5 mmol/L and triglyceride level, greater than 2.0 mmol/L) was present in 52% of subjects. Low-density lipoprotein cholesterol levels exceeded 3.5 mmol/L in 69% of men and in 71% of women. In terms of five 10-year age intervals, mean plasma triglyceride and cholesterol levels were elevated significantly in patients who had undergone a coronary-artery grafting procedure compared with those of subjects in the National Heart Foundation study. The mean high-density lipoprotein cholesterol levels were markedly-lower compared with those of the subjects in the National Heart Foundation study. Of those patients whose plasma cholesterol levels were less than 5.5 mmol/L, 97% of patients had high-density lipoprotein cholesterol levels that were less than the mean level for subjects in the National Heart Foundation study. Thus, a very-high proportion of patients who underwent coronary-artery bypass surgery had lipid abnormalities which required intervention postoperatively.

Adrenergic beta-Antagonists↗
PubMed1989

Lipids, lipoproteins and apolipoproteins A-I and B and apolipoprotein losses in continuous ambulatory peritoneal dialysis.

Comparison of lipid, lipoprotein and apolipoprotein levels was made between 3 groups: continuous ambulatory peritoneal dialysis patients (n = 5); haemodialysis patients (n = 15) and normals (n = 31). Continuous ambulatory peritoneal dialysis (CAPD) patients showed significantly elevated total cholesterol, low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apo B) levels compared with haemodialysis and normal groups. Both CAPD and haemodialysis (HD) showed reduced levels of high density lipoprotein (HDL)-cholesterol and apolipoprotein A-I (apo A-I). Measurement of apo A-I and apo B in dialysate during a 6 h CAPD session indicated significant losses of apo A-I to dialysate with negligible losses of apo B. Grossly elevated apo B and reduced apo A-I indicates that CAPD patients are at increased risk of coronary heart disease and that their risk is probably greater than for haemodialysis patients.

Apolipoproteins A↗
PubMed1987

Slower catabolism of apo B48 than of apo B100 in triglyceride-rich lipoproteins during heparin infusions in type 5 hyperlipoproteinemic subjects.

The catabolism of chylomicrons plus remnants and of VLDL was studied in four subjects with type 5 hyperlipoproteinemia. Large triglyceride-rich lipoproteins Sf greater than 60 were labeled with 125I, reinjected, and the removal of radioactivity in apo B48 and in apo B100 was measured before and during intravenous heparin. The constant infusion of heparin stimulated lipolytic activity and accelerated the disappearance of apo B100 radioactivity (VLDL and their remnants) from the Svedberg flotation unit (Sf) greater than 60 fraction by 27%, 33%, 51%, and 55% in the four subjects. However, the removal rate of radioactivity in apo B48 (chylomicrons and their remnants) was unaffected by heparin in three subjects; in the fourth the fall in radioactivity was less in apo B48 than in apo B100. There were corresponding rises with heparin in Sf 12 to 60 apo B48 radioactivity in only one subject. Thus, increased plasma lipolytic activity accelerated chylomicron (remnant) catabolism very much less than of VLDL (remnant) removal of type 5 hyperlipoproteinemic subjects. It suggests that a major defect leading to type 5 hyperlipoproteinemia is failure of chylomicrons to become degraded to the point where the particles can interact optimally with the hepatic chylomicron remnant receptor.

Adult↗
PubMed1985

Metabolism of human plasma triacylglycerol-rich lipoproteins in rodent macrophages: capacity for interaction at beta-VLDL receptor.

The capacity of human plasma triacylglycerol-rich lipoproteins to be metabolized by rat macrophages was studied with plasma triacylglycerol-rich lipoproteins obtained from subjects with fasting chylomicronemia or from normal subjects after a fat meal. Triacylglycerol-rich lipoproteins were separated by chromatography into two fractions designated TRL1 and TRL2; from their composition and changing concentration during alimentary lipemia, TRL1 contained a higher proportion of chylomicron remnants than TRL2. Degradation of 125I-labeled TRL1 was greater than that of 125I-labeled TRL2. In competition studies with 125I-labeled beta-VLDL from cholesterol-fed rabbits, unlabeled TRL1 displaced beta-VLDL as completely as did unlabeled beta-VLDL, being slightly more potent than TRL2, which contained less apolipoprotein E than TRL1. This reflected common interaction at receptors that probably included both beta-VLDL and B/E receptors, since: (1) in fresh macrophages, VLDL from hypertriglyceridemic subjects partially displaced beta-VLDL; (2) in B/E receptor-repressed macrophages, TRL1 maintained capacity to totally displace beta-VLDL. This was confirmed in experiments with J774 murine macrophages in which triacylglycerol-rich lipoproteins and beta-VLDL displaced each other equally, whereas LDL was ineffective in displacing beta-VLDL. Furthermore, monoclonal antibodies raised against apolipoprotein B48 and reacting strongly with LDL, failed to inhibit the binding of triacylglycerol-rich lipoprotein to the macrophages. This indicates an interaction through apolipoprotein E which is present in high concentration in triacylglycerol-rich lipoprotein as well as in beta-VLDL. It applies to triacylglycerol-rich particles derived from either the intestine (chylomicron remnants) or the liver (VLDL remnants from hypertriglyceridemic subjects).

Animals↗
PubMed1983

Slower removal of intestinal apolipoprotein B-48 than of apolipoprotein B-100 in severely hypertriglyceridemic subjects.

Apolipoprotein B, the major structural protein of triacylglycerol-rich lipoprotein, occurs in two immunologically distinct forms, termed apolipoproteins B-100 and B-48. In man, the former is associated with triacylglycerol-rich lipoproteins of hepatic origin and the latter with intestinal triacylglycerol-rich lipoproteins. We have studied the rates of removal of the two proteins when 125I-labelled triacylglycerol-rich lipoproteins were reinjected into six severely hypertriglyceridemic subjects showing hyperchylomicronemia, and into two normal subjects. The specific radioactivities of apolipoproteins B-100 and B-48 were determined over periods of up to 30 h. In all six hyperlipemic subjects the removal of apolipoprotein B-100 was either significantly faster than that of apolipoprotein B-48 (in four) or similar in the two who cleared triacylglycerol-rich lipoproteins very slowly. When triacylglycerol-rich lipoproteins from two hyperlipemic subjects (in whom apolipoprotein B-48 was cleared more slowly) were injected into two normal subjects both B apolipoproteins were cleared at similar rates. Since apolipoprotein B-48 appears to be a marker for remnants of intestinal particles, its slower removal than that of apolipoprotein B-100 in severe hypertriglyceridemia suggests that one metabolic defect associated with the hyperchylomicronemia is defective removal of chylomicron remnants.

Adult↗
PubMed1983

Preliminary report increased transport of intermediate density lipoprotein (LDL) with cholesterol loading.

Although cholesterol loading in man generally leads to an increase in plasma cholesterol and low density lipoprotein cholesterol in particular, the mechanism for this is unknown. Because IDL formation rises in cholesterol-fed rats we have measured the transport of IDL apoprotein B in 8 men during two dietary periods containing either 200 mg or 1700 mg cholesterol per day. Radioiodinated IDL (Sf 12-20 or Sf 12-60) were reinjected and transport calculated from 48 hr specific radioactivity-time curves of apoprotein B in reisolated IDL. With cholesterol loading the IDL cholesterol and apoprotein B concentrations rose in 7 of 8 subjects (substantially in only 2). However IDL transport was stimulated more consistently and significantly (p less than 0.01), rising by at least 50% in 5 subjects. Furthermore the change in plasma total cholesterol concentration was significantly correlated with the change in IDL transport (r = +0.70, p less than 0.05). Since LDL are derived from IDL, the cholesterol-induced rise in IDL formation may explain the increase in LDL concentration with dietary cholesterol.

Adult↗
PubMed1983

Heterogeneity of very-low-density lipoprotein metabolism in hyperlipidemic subjects.

Very-low-density lipoproteins (VLDL) are triglyceride-rich lipoproteins that have been shown, by physicochemical means, to comprise more than one group of particles. Because of the potential atherogenicity of catabolized VLDL, we used the technique of heparin-affinity chromatography to separate VLDL into two classes of particles, one of which appears to contain partly catabolized VLDL. This observation is based on the higher cholesterol/triglyceride and higher apoprotein E/apoprotein C ratios in VLDL particles that are bound to heparin, resembling in this way intermediate-density lipoproteins (IDL), which are certainly derived in the main through VLDL catabolism. Further studies showed separate metabolic characteristics for the unbound and heparin-bound VLDL particles. Radiolabeled whole VLDL or unbound particles were reinjected into seven hypertriglyceridemic subjects and the kinetics studied in serial samples of plasma over the next 18-48 hours. The specific radioactivity-time curves of apoprotein B in the unbound and bound particles showed that the bound particles were derived wholly or partly from the unbound particles and in turn, were the precursors of IDL. This confirmed that heparin-bound VLDL particles represented VLDL undergoing catabolism, although in one subject about one-half of the bound particles appeared to have an origin other than through VLDL catabolism. These studies show that VLDL metabolism is heterogeneous, that the kinetics of total VLDL must be interpreted accordingly, and that the technique of heparin-affinity chromatography can be used for more detailed studies of VLDL.

Adult↗
PubMed1982

Changes in the plasma lipoprotein distribution of apolipoproteins C-II, C-III1, C-III2 and apolipoprotein B after heparin-induced lipolysis.

The group of C apolipoproteins are involved in the catabolism of triacylglycerol-rich lipoproteins, C-II activating triacyglycerol lipolysis and C-III possibly preventing premature removal of the particle. In normal subjects, C-II, C-III1 and C-III2 exchange between very low density (VLDL) and high density lipoprotein (HDL) at similar rates and catabolism appears to occur with HDL. In the present studies in one normal and in four subjects with moderate-to-severe hypertriglyceridemia, the metabolism of the C apolipoproteins was studied before and during maximal lipolysis induced with heparin. Radioiodinated triacylglycerol-rich lipoproteins were injected and the specific activity-time curves for C-II, C-III1, C-III2 and B proteins were analyzed in triacylglycerol-rich lipoproteins and HDL. Heparin infusion caused rapid and proportional transfer of each C apolipoprotein from triacylglycerol-rich lipoproteins to HDL. In the two most hyperlipemic men, a substantial fraction (over 90%) of apolipoprotein C mass lost from triacylglycerol-rich lipoproteins was not recoverable in HDL, whereas in the normal subject this was less than 15% and intermediate in the other two hypertriglyceridemic men. This indicates a new potential catabolic pathway for C apolipoproteins, direct loss from the circulation during remnant particle removal, which was also evident from B apolipoprotein studies. Furthermore, unlike in the normal subject transfer of C apolipoprotein radioactivity from triacylglycerol-rich lipoproteins to HDL was greater than that of mass, also suggesting heterogeneity in C apolipoprotein catabolism. The studies show that C apolipoprotein metabolism may be disturbed in severely hypertriglyceridemic subjects: the lack of conservation of these proteins within HDL may exacerbate the degree of hyperlipoproteinemia.

Adult↗
PubMed1982

Changes in very low density lipoproteins with cholesterol loading in man.

We have studied the effects of cholesterol loading in man, seeking changes in VLDL that may define a population of particles that resemble the atherogenic beta-VLDL in experimental animals. Comparisons were made in 6 men during two diets, containing either 200 mg or 1700 mg cholesterol daily. Although the total plasma cholesterol did not rise significantly over 4 wk of cholesterol loading (mean +/- SD 178 +/- 41 to 194 +/- 48 mg/dl), distinct changes in lipoprotein composition occurred; (1) HDL cholesterol rose significantly (34 +/- 4 to 41 +/- 5) and plasma apoprotein AI rose from 118 +/- 10 to 129 +/- 9 mg/dl. (2) Within VLDL, the proportion of apoproteins E:C rose from 0.18 to 0.32 (p less than 0.005), though the apoprotein E concentration did not change, (3) Within VLDL, the ratio of cholesteryl esters:triglycerides rose, (4) Within VLDL (Sf 20-400) a population of particles that bound to heparin on heparin-sepharose columns increased threefold; since these particles were richer in apoprotein E and in cholesteryl ester than were VLDL not bound to heparin, we conclude that cholesterol loading leads to an increase in smaller VLDL particles, possibly partly catabolized VLDL or independently secreted IDL, that resemble findings in cholesterol fed animals, and (5) Transport kinetics of apoprotein B in VLDL studied in four subjects did not show a rise in production but this does not rule out increased secretion of a cholesteryl ester, apoprotein E enriched subpopulation of VLDL.

Adolescent↗
PubMed1981

Low density and high density lipoprotein kinetics and sterol balance in vegetarians.

Vegetarians have lower than average plasma lipid levels. Possible mechanisms were studied by measuring the kinetics of LDL-B protein and HDL-AI protein in 7 young male vegetarians and 6 omnivorous control subjects; sterol balances were also determined in a further study with the 6 additional control subjects whose intake of cholesterol was low. Plasma total cholesterol, LDL cholesterol and LDL-B protein were significantly lower in the vegetarians and plasma AI protein concentrations also tended to be lower. The flux or production of LDL was significantly lower, 9.1 +/- 2.3 mg/kg/d (mean +/- SD) compared to 11.8 +/- 0.6 mg/kg/d in the controls and appeared to explain the low levels of LDL. The fractional removal rate of HDL-AI protein was significantly greater in the vegetarians (0.043 +/- 0.011 versus 0.027 +/- 0.011 for the fractions of pool 1 cleared per hour) and appeared to account for the low plasma AI levels. In the second study, bile acid excretion was significantly lower in the vegetarians and estimated cholesterol synthesis was in the low normal range. Low rates of LDL-B protein formation have been reported in other subjects with low LDL cholesterol concentrations and in the vegetarians presumably reflect the composite of several dietary factors.

Adult↗
PubMed1981

Metabolism of C-apolipoproteins: kinetics of C-II, C-III1 and C-III2, and VLDL-apolipoprotein B in normal and hyperlipoproteinemic subjects.

The turnover and metabolism of the individual C apolipoproteins (C-II, C-III1, and C-III2) were studied following the injection of 125I-labeled VLDL into 15 normal and hyperlipoproteinemic subjects. The C apolipoproteins from very low density lipoprotein (VLDL) and high density lipoprotein (HDL) were separated by analytical isoelectric focusing, and subsequent densitometric scanning and radioassay of the stained bands yielded values for specific activity. In 13 of 15 subjects, kinetics of C-II, C-III1, and C-III2 were best described by a one-pool model, whereas two subjects showed biexponential kinetics. The specific activity-time curves for VLDL and HDL were super-imposable, indicating rapid exchange of all C apolipoproteins in hyperlipidemic as well as in normal subjects. In each subject the half-life was similar for C-II, C-III1, and C-III2, which suggests similar synthesis and catabolic mechanisms for each C apolipoprotein. The mass of exchangeable C-II (range 1.0-5.8 mg/kg), C-III1 (2.6-20 mg/kg), and C-III2 (2.0-13 mg/kg) increased with plasma triglyceride concentrations. Values for flux of C-II were 1.0-2.8 mg/d per kg, for C-III1 1.6-5.6 mg/d per kg, and for C-III2 1.2-3.1 mg/d per kg, but they were not related to levels of plasma triglyceride. However the irreversible fractional catabolic rates were inversely related to C apolipoprotein (and triglyceride) mass, suggesting that expansion in C apolipoprotein pool size is related to slower removal, due to the longer residence time of triglyceride-rich VLDL particles in plasma. This was confirmed by similar findings for B apolipoprotein kinetics in VLDL carried out simultaneously.

Adult↗
PubMed1980

Turnover of apoproteins A-I and A-II of high density lipoprotein and the relationship to other lipoproteins in normal and hyperlipidemic individuals.

The kinetics of the major apoproteins of high density lipoproteins (HDL), A-I(apoA-I) and A-II(apoA-II), were studied from the specific activity-time curves of these apoproteins, after reinjection of radioiodine-labeled HDL. In all 20 subjects, HDL apoprotein kinetics conformed to a two-pool model. The total fractional removal rates for the two apoproteins were similar, although the irreversible fractional removal rate appeared to be slightly greater for apoA-I. The mean transport for A-I and A-II was 12.2 mg/kg/day and 5.0 mg/kg/day, respectively. The mass of the apoprotein pools was strongly correlated with apoprotein production rate and also, to a lesser degree and inversely, with the irreversible fractional catabolic rate. Transport was directly correlated with body weight. Higher fractional catabolic rates, including the transfer rates between the two pools, were observed in five hypertriglyceridemic subjects; in contrast, five subjects with familial hypercholesterolemia tended to show lower fractional catabolic rates. These findings were supported by (1) a strongly positive correlation between the transport rates of HDL A-I and of very low density lipoprotein (VLDL) apoB, determined simultaneously in 10 subjects; and (2) a significant inverse correlation between the irreversible fractional removal rate of HDLA-I and the concentration of low density lipoprotein (LDL) apoB, measured in 15 subjects. These observations underline the metabolic interrelationships of the major lipoprotein classes. Two subjects with familial hyperalphalipoproteinemia showed enlarged pool sizes, but normal transport, with irreversible fractional removal rates that were in the lower range for the group of 20 subjects.

Adult↗