Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of the remmant kidney tissue in uremic patients undergoing hemodialysis treatment has rarely been considered to influence the changes in lipoprotein and lipid metabolism. Twenty hemodialyzed patients with remnant kidneys and 11 anephric patients were studied to examine whether the presence or the absence of remnant kidney leads to qualitative or quantitative changes of the lipids and lipoproteins. Anephric patients showed a significantly higher triglyceride level, 3.66 +/- 0.49 (SEM) mmol/L v 2.34 +/- 0.09 mmol/L in patients with remnant kidneys (P less than .01), higher very-low-density lipoprotein (VLDL) triglycerides, 1.24 +/- 0.30 mmol/L v 0.69 +/- 0.09 (P less than .04), and higher HDL-triglycerides, 1.22 +/- 0.29 mmol/L v 0.66 +/- 0.09 mmol/L (P less than .04). APO-AI was significantly decreased in anephric patients, 95.2 +/- 13.3 mg/dL v 129.7 +/- 6.02 mg/dL in patients with remnant kidneys (P less than .01). APO-B was similar in both groups. All APO-C and APO-E were significantly lower in anephric patients, APO-CI 6.13 +/- 0.87 mg/dL v 8.47 +/- 0.42 mg/dL in patients with remnant kidneys (P less than .01), APO CII 1.00 +/- 0.01 mg/dL v 10.0 +/- 0.01 mg/dL (P less than .0001), APO-CIII 10.12 +/- 1.43 mg/dL v 26.0 +/- 2.86 mg/dL (P less than .0005), and APO-E 8.0 +/- 0.02 mg/dL v 12.0 +/- 0.01 mg/dL (P less than .03). These results point out important differences between women and men. In women binephrectomy promotes a decreased concentration of all APO-C but has no influence on APO-AI concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in lipoproteins induced by the remnant kidney tissue or binephrectomy in chronic uremic patients treated by hemodialysis. 249 13

The effect of metoprolol, a beta 1-blocker, on atherogenesis was evaluated in rabbits fed a diet supplemented with 0.25% cholesterol and 3% coconut oil for 21 weeks. After 7 weeks on the diet, the rabbits were randomly divided into treated (n = 22) and untreated (n = 22) groups. Treated animals received metoprolol subcutaneously by an osmotic pump for 14 weeks, resulting in a plasma level of 774 +/- 69 nM during the investigation. Plasma concentrations of cholesterol, triglycerides, and phospholipids did not differ between the two groups. Nor were there any significant differences between the two groups in plasma concentrations of apolipoprotein A-I, apolipoprotein B, apolipoprotein C-III, and apolipoprotein E measured by electroimmunoassay. At the end of the study, the aortas were cut into three portions and the extent of atherosclerosis was determined by morphometry. The group that had received metoprolol had significantly (p less than 0.015) less atherosclerosis in the aorta (ascending plus arch 37.8 +/- 6.8%, thoracic 32.9 +/- 6.1%, abdominal 19.8 +/- 6.1% of total intimal area; mean +/- SEM) than the controls (ascending plus arch 54.9 +/- 7.1%, thoracic 48.0 +/- 6.2%, abdominal 25.9 +/- 5.5%).
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PMID:Effect of metoprolol on diet-induced atherosclerosis in rabbits. 334 91

The effect of isocaloric high and low carbohydrate (Carb) diets on the structure and apoprotein composition of plasma high density lipoproteins (HDL) was assessed in four healthy men. The high Carb diet contained 65% calories as Carb and 15% as fat; the low Carb was 15% and 65%, respectively, with protein fixed at 20% of calories in each case. Cholesterol was 400 mg/day and the P/S ratio of the fat was 0.4. Each diet was sequentially consumed for periods of 3 weeks. At the end of each 3-week study period, plasma HDL2 and HDL3 were isolated by zonal ultracentrifugation and their apoprotein and lipid compositions were determined. Compared to the low Carb diet, the high Carb diet was associated with an increase in the size of HDL2 (116.0 +/- 1.8 vs. 109.1 +/- 1.8 A) and in the content (mean weight % +/- SEM) of apoE (2.81 +/- 0.71 vs. 1.79 +/- 0.49, P less than 0.01) and of apoC-II (1.73 +/- 0.09 vs. 1.11 +/- 0.12, P less than 0.01). HDL2 apoC-III content was not significantly different on the two diets (6.49 +/- 0.50 vs. 7.42 +/- 1.21). On the two diets, HDL3 size and HDL3 apoE content were not significantly changed. HDL3 apoC-II and apoC-III, however, were higher on the high Carb diet, P less than 0.05. The ratio (by weight) of HDL2 apoE/HDL2 apoC-II + C-III increased on the high Carb diet compared to the low Carb diet (0.344 +/- 0.058 vs. 0.228 +/- 0.053, P less than 0.01). We suggest that the increased amount of apolipoprotein E in HDL2 may influence its rate of catabolic clearance and may account for the well-known decrease in plasma HDL-cholesterol in subjects on high Carb diets.
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PMID:Effect of a high carbohydrate diet on the content of apolipoproteins C-II, C-III and E in human plasma high density lipoprotein subfractions. 684 45

Eight male cynomolgus monkeys (Macaca fascicularis) on a normal chow diet were orally administered gemfibrozil daily using a weekly rising dose protocol for 3 weeks (50, 125, and 200 mg/kg per day). At these drug doses, Lp[a] levels were reduced: 83.7% +/- 3.2 (SEM), (P < 0.024); 63.7% +/- 4.1 (P < 0.013); and 36.2% +/- 1.1 (P < 0.002), respectively, of pretreatment values. Lp[a] reduction was directly related to blood gemfibrozil concentration (range 36-428 microM, r = 0.969) and occurred without concomitant changes in apolipoprotein B. Three weeks posttreatment Lp[a] levels returned to pretreatment values. A specific ribonuclease protection assay demonstrated that liver apolipoprotein[a] (apo[a]) mRNA expression was decreased in all animals to an average of 19.1% +/- 3.0 (P < 0.0026), of pretreatment values after the 200 mg/kg treatment, whereas, albumin, apolipoprotein A-I, apolipoprotein E, and glyceraldehyde-3-phosphate dehydrogenase mRNAs were unchanged. Lp[a] levels were unaffected by gemfibrozil in HepG2 cells permanently transfected with an apo[a] 10-kringle cDNA construct containing partial 5'- and 3'-untranslated sequences and under control of a constitutive CMV promoter. However, both Lp[a] and apo[a] mRNA in primary cynomolgus monkey hepatocytes were coordinately lowered in a dose-dependent fashion by gemfibrozil. Thus, Lp[a] can be regulated by gemfibrozil at the level of apo[a] mRNA expression.
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PMID:Gemfibrozil significantly lowers cynomolgus monkey plasma lipoprotein[a]-protein and liver apolipoprotein[a] mRNA levels. 766 7

Polyunsaturated dietary fat (n-3 and n-6) results in less atherosclerosis in monkeys compared to lard (Parks, J.S., Kaduck-Sawyer, J., Bullock, B.C., and Rudel, L.L., Arteriosclerosis 10, 1102-1112; Rudel, L.L., Parks, J.S., Johnson, F.L., and Babiak, J., J. Lipid Res. 27, 465-474, 1986). We hypothesized that this was due, in part, to a decreased reactivity of low density lipoproteins (LDL) with arterial proteoglycans (PG). To test this hypothesis, cynomolgus monkeys were fed diets containing lard, safflower oil (n-6 polyunsaturated; Poly), menhanden fish oil (FO), or oleic acid-rich safflower oil (oleinate; Mono) for 14 mon, and plasma LDL were isolated and characterized. Several properties of LDL thought to be important in the interaction of LDL with arterial PG were measured including LDL particle size, chemical composition, sialic acid content, density distribution, apolipoprotein E (apoE) content and cholesteryl ester transition temperature. Plasma LDL cholesterol concentrations (mg/dL) after 14 mon of diet consumption averaged (mean +/- SEM): FO (366 +/- 45), Lard (352 +/- 27), Poly (279 +/- 24), and Mono (230 +/- 43). The composition of LDL was similar among diet groups except that FO LDL were relatively depleted of cholesteryl ester and enriched in protein and were smaller in size. LDL sialic acid content was similar among diet groups (4.5-5.0 micrograms/mg LDL protein). The LDL apoE/B molar ratio, a measure of the apoE content per LDL particle averaged: Mono (3.0 +/- 1.0), Poly (2.0 +/- 0.1), Lard (1.8 +/- 0.5), and FO (1.0 +/- 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary polyunsaturated fat decreases interaction between low density lipoproteins and arterial proteoglycans. 781 98

We analysed a well-characterized group of 83 patients (43 men, 40 women; mean age +/- SEM: 65.5 +/- 0.6 years at the 10-year examination) with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and in 123 control subjects (56 men, 67 women; mean age +/- 0.9 years) retrospectively for the relationship of apolipoprotein E (apo E) genotypes (E2/3, E3/3 vs E3/4, E4/4) to the incidence of clinical macrovascular disease and its risk factors and the incidence of microvascular complications of diabetes during the first 10 years of NIDDM, as well as carotid intima-media thickness measured by B-mode ultrasound at the 10-year examination. In patients with NIDDM, apo E4 genotype showed no relationship to clinical events or carotid intima-media thickness. However, in the control subjects with apo E4, the incidence of non-fatal myocardial infarction during the follow-up was increased (apo E4 positivity: 17.1%; apo E4 negativity 5.1%; p = 0.035) and they had higher common carotid intima-media thickness than those with apo E2/3 or apo E3/3 (1.15 +/- 0.05 mm vs 1.01 +/- 0.03 mm, p = 0.008). Apo E genotype groups showed no relationship to microvascular complications of diabetes, although control subjects with apo E4 positivity showed a higher frequency of microalbuminuria than those lacking apo E4. We conclude that apo E4 was a marker of vascular disease and increased atherosclerosis in non-diabetic subjects, whereas in the diabetic patients these relationships were absent. It is likely that NIDDM per se influences the vascular risk so overwhelmingly that the effects of other risk factors are obscured.
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PMID:Divergent association of apolipoprotein E polymorphism with vascular disease in patients with NIDDM and control subjects. 930 Feb 24

Posterior cingulate cortex is the site of earliest reductions in glucose metabolism and qualitatively different laminar patterns of neurodegeneration in Alzheimer's disease (AD). This study used multivariate analyses of area 23 in 72 cases of definite AD to assess relationships between laminar patterns of neurodegeneration, neurofibrillary tangle (NFT) and senile plaque (SP) densities, age of disease onset and duration, and apolipoprotein E (ApoE) genotype. No age-related changes in neurons occurred over four decades in 17 controls and regression analysis of all AD cases showed no relationships between neuron, SP, and tau-immunoreactive NFT densities. Principal components analysis of neurons in layers III-Va and eigenvector projections showed five subgroups. The subgroups were independent because each had a full range of disease durations and qualitatively different laminar patterns in degeneration suggested disease subtypes (ST). Cases with most severe neuron losses (STSevere) had an early onset, most SP, and highest proportion of ApoE epsilon4 homozygotes. Changes in the distribution of NFT were similar over disease course in two subtypes and NFT did not account for most neurodegeneration. In STII-V with moderate neuron loss in most layers, cases with no NFT had a disease duration of 3.5 +/- 0.9 years (mean +/- SEM), those with most in layers IIIc or Va had a duration of 7.3 +/- 1 years, and those with most in layers II-IIIab had a duration of 12.1 +/- 1 years. In STSevere, cases with highest NFT densities in layers II-IIIab also were late stage. Finally, epsilon4 homozygotes were most frequent in STSevere, but four statistical tests showed that this risk is not directly involved in neurodegeneration. In conclusion, multivariate pattern recognition shows that AD is composed of independent neuropathological subtypes and NFT in area 23 do not account for most neuron losses.
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PMID:Multivariate analysis of laminar patterns of neurodegeneration in posterior cingulate cortex in Alzheimer's disease. 974 63

We measured somatostatin-like immunoreactivity, using a radioimmunoassay which does not cross react with cortistatin-like immunoreactivity, in postmortem frontal cortex (Brodmann area 9) from 32 patients, of different apolipoprotein E genotypes, and presenting with different degrees of cognitive impairment. Eleven subjects and eight patients presented with no (controls) or limited memory impairments (Borderline), respectively. Six patients with clinical criteria for possible Alzheimer's disease also presented with clinical or brain imaging of cerebrovascular disease (mixed dementia) and seven patients were classified as Alzheimer's disease (AD). In the 6 months preceeding their deaths, all subjects had been evaluated by Folstein's Mini Mental State examination (MMS). Sixty nine percent of patients with MMS >20 did not carry the epsilon 4 allele while 66% of patients with MMS <10 did. Somatostatin concentrations (ng/mg wet weight) were significantly lower in the patients carrying the epsilon 4 allele (E2/3: 0.71 +/- 0.05, n = 19 vs. E4: 0.42 +/- 0.06, n = 13; mean +/- SEM, P < 0.001). These results, which are reminiscent of those obtained on cholinergic markers, suggest that apolipoprotein E4 is involved in the somatostatinergic dysfunction early after the onset in AD.
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PMID:Loss of somatostatin-like immunoreactivity in the frontal cortex of Alzheimer patients carrying the apolipoprotein epsilon 4 allele. 983 17

The increased risk of hyperlipidemia on the development of complications of atherosclerosis is well established. Cholesterol-lowering therapies lead to a decrease in the incidence of vascular thrombotic events that is out of proportion to the reduction in plaque size. This suggests that the occurrence of acute thrombosis overlying a disrupted plaque is influenced by changes in lipid levels. The influence of acute hyperlipidemia on the development of thrombosis overlying an atherosclerotic plaque in vivo has not been extensively studied. We used a murine model of vascular injury induced by a photochemical reaction to elicit thrombus formation overlying an atherosclerotic plaque. Fifteen apolipoprotein E-deficient mice were maintained on normal chow until the age of 30 weeks. Five days before the induction of thrombosis, 6 mice were started on a high fat diet, and 9 mice were continued on normal chow. Mice then underwent photochemical injury to the common carotid artery immediately proximal to the carotid bifurcation, where an atherosclerotic plaque is consistently present. Mice maintained on normal chow developed occlusive thrombi, determined by cessation of blood flow, 44+/-5 minutes (mean+/-SEM) after photochemical injury, whereas mice fed a high fat chow developed occlusive thrombosis at 27+/-3 minutes (P<0.02). Histological analysis confirmed the presence of acute thrombus formation overlying an atherosclerotic plaque. These studies demonstrate a useful model for assessing the determinants of thrombosis in the setting of atherosclerosis and show that acute elevations in plasma cholesterol facilitate thrombus formation at sites of atherosclerosis after vascular injury.
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PMID:Hyperlipidemia promotes thrombosis after injury to atherosclerotic vessels in apolipoprotein E-deficient mice. 1089 25

Wild-type C57BL mice are known to be susceptible to diet-induced atherosclerosis, whilst C3H mice are resistant. We investigated the effect of these background strains on the hyperlipidaemia and atherosclerosis that develops in mice deficient in apolipoprotein E (apoE(-/-)). Male and female apoE(-/-) mice on C3H/HeNHsd (C3H) and C57BL/6J (C57) backgrounds were fed atherogenic Western diet for 12 weeks. Serum cholesterol and triglyceride concentrations were measured and atherosclerosis quantified in the aortic sinus. C3H apoE(-/-) mice fed normal diet had 1.5 2 fold higher serum cholesterol levels than C57 apoE(-/-) mice and 4-5 fold higher serum triglyceride concentrations. Feeding Western diet caused a 4-5 fold increase in serum cholesterol in all mice, but levels of triglyceride were either attenuated or were unaffected in C3H apoE(-/-) and C57 apoE(-/-) mice, respectively. C3H apoE(-/-) mice had approximately 2 fold higher serum cholesterol and 4 fold higher triglyceride concentrations than the C57 apoE(-/-) mice throughout the study. Serum triglyceride concentrations were 35-108% higher in male C3H apoE(-/-) than female C3H apoE(-/-) mice. Most of the lipids were present in the very low density lipoprotein (VLDL)/chylomicron fraction in both strains of mice whether they were fed normal or Western diet. Notwithstanding the lower plasma lipid concentrations, atherosclerotic lesion areas were more than 2-fold larger in C57 apoE(-/-) than in C3H apoE(-/-) mice (males 68 +/- 11 x 10(3) vs 30 +/- 6 x 10(3) females 102 +/- 12 x 10(3) vs 41 +/- 8 x 10(3) microm2. mean +/- SEM).
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PMID:C3H apoE(-/-) mice have less atherosclerosis than C57BL apoE(-/-) mice despite having a more atherogenic serum lipid profile. 1092 15


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