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Biomedical subjects

E D Janus

Publications and source records attributed to E D Janus.

At least 73 records · Page 4Linked to original sources
PubMed1992

Plasma apolipoprotein (a) is increased in type 2 (non-insulin-dependent) diabetic patients with microalbuminuria.

Patients with Type 2 (non-insulin-dependent) diabetes mellitus complicated by microalbuminuria or albuminuria, have an increased risk of developing macrovascular disease and of early mortality. Because lipoprotein abnormalities have been associated with diabetic nephropathy, this study tested the hypothesis that levels of apolipoprotein (a) are elevated in patients with Type 2 diabetes and increased levels of urinary albumin loss. Levels of apolipoprotein (a) in diabetic patients with microalbuminuria (n = 26, geometric mean 195 U/l, 95% confidence interval 117-324) and albuminuria (n = 19, 281 U/l, 165-479) were higher than in non-diabetic control subjects (n = 140, 107 U/l, 85-134, p < 0.05), and in the albuminuric group than diabetic patients without urinary albumin loss (n = 58, 114 U/l, 76-169, p < 0.05). Patients with microalbuminuria and albuminuria had levels comparable with patients undergoing elective coronary artery graft surgery (n = 40, 193 U/l, 126-298). Apolipoprotein (a) levels were higher in diabetic patients with macrovascular disease than in those without (n = 49, 209 U/l, 143-306 vs n = 54, 116 U/l, 78-173, p < 0.05). These preliminary results suggest that raised apolipoprotein (a) levels of Type 2 diabetic patients with microalbuminuria and albuminuria may contribute to their propensity to macrovascular disease and early mortality.

Aged↗
PubMed1991

Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria.

Patients with insulin-dependent diabetes mellitus (IDDM) have a significantly increased risk of macrovascular disease, particularly if they have persistent proteinuria. To determine whether altered levels of apolipoprotein(a) [apo(a)], the plasminogenlike glycoprotein of the potentially atherogenic lipoprotein(a); contribute to the increased risk of atherosclerosis, apo(a) levels were measured in 107 patients with IDDM and compared with nondiabetic control subjects and male elective coronary artery graft patients. Apo(a) levels were increased in diabetic patients with microalbuminuria (geometric mean 245 U/L, 95% confidence interval [CI] 142-427, n = 30) and albuminuria (mean 196 U/L, 95% CI 97-397, n = 18) with levels comparable to patients with coronary artery disease (mean 193 U/L, 95% CI 126-298, n = 40), which were higher than in the control group (mean 107 U/L, 95% CI 85-134, n = 140; P = 0.016). Apo(a) levels in diabetic patients without microalbuminuria (mean 86 U/L, 95% CI 63-116, n = 59) were comparable with the control population and less than in those with microalbuminuria (P less than 0.001) and albuminuria (P = 0.014). The elevated apo(a) levels found in patients with IDDM and increased urinary albumin loss may contribute to their heightened risk of macrovascular disease.

Adult↗
PubMed1990

Apolipoprotein E2-Dunedin (228 Arg replaced by Cys): an apolipoprotein E2 variant with normal receptor-binding activity.

Homozygosity for the apolipoprotein (apo) E variant apoE2(158 Arg----Cys) invariably gives rise to dysbetalipoproteinemia, and when associated with obesity or a gene for hyperlipidemia, results in type III hyperlipoproteinemia. The association of the E2/2 phenotype with type IV/V hyperlipoproteinemia rather than type III hyperlipoproteinemia in identical twin brothers led us to investigate the primary structure of their apoE. Lipoprotein electrophoresis on agarose gels confirmed the presence of increased very low density lipoproteins (VLDL) and chylomicrons but little, if any, beta-VLDL, indicating that these subjects did not have dysbetalipoproteinemia. When the apoE from these twins was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis on a system that can distinguish apoE2(158 Arg----Cys) from all other known apoE variants, it gave rise to two components. One had the unique mobility of apoE2(158 Arg----Cys), and one migrated in the position of the other variants of apoE (and normal apoE3), indicating that the brothers were heterozygous for apoE2(158 Arg----Cys) and a second apoE2 isoform. Cysteamine modification and isoelectric focusing showed that, like apoE2(158 Arg----Cys), the second apoE2 isoform also contained two cysteine residues. The structural mutation in the second apoE2 isoform was determined by peptide sequencing. Like normal apoE3, this variant had arginine at position 158, but differed from apoE3 by the substitution of cysteine for arginine at position 228. Total apoE isolated from the brothers had the same receptor-binding activity in a competitive binding assay as a 1:1 mixture of normal apoE3 and apoE2(158 Arg----Cys).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
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↗
PubMed1988

Cholesterol in the plasma very low density lipoprotein fraction in patients with type III hyperlipoproteinemia: analysis of factors which modulate its concentration.

Anthropometric data, plasma lipoprotein lipid levels, and post-heparin lipoprotein lipase (PHLPL) activity were measured in nine patients with type III hyperlipoproteinemia (HLP) and two hypocholesterolemic subjects with the apo-E2/2 phenotype. Five type III HLP patients were treated with clofibrate. Log PHLPL activity was inversely correlated (r = -0.667, p less than 0.05) and age was positively correlated (r = 0.706, p less than 0.05) with cholesterol levels in the VLDL fraction of plasma from type III HLP patients. The correlation between log PHLPL and VLDL cholesterol levels remained significant when age was held constant in partial correlation analysis. Together age and log PHLPL activity accounted for 77% of individual variation in VLDL cholesterol levels in the type III patients. Clofibrate treatment raised PHLPL activity (+48%, p less than 0.05) and reduced the levels of VLDL cholesterol (-67%, P less than 0.05), VLDL triglycerides (-40%, P less than 0.02), and the ratio cholesterol/triglyceride in VLDL (-50%, P less than 0.05) in five type III HLP patients. Mean PHLPL activity was higher in the hypocholesterolemic subjects with the apo-E2/2 phenotype compared to the type III HLP patients. These results suggest that lipoprotein lipase activity and factors associated with age modulate the levels of abnormal and atherogenic remnant particles (beta-VLDL) in the VLDL plasma fraction of type III HLP patients.

Adult↗
PubMed1987

Apolipoprotein E2-Christchurch (136 Arg----Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia.

The primary structure of apolipoprotein E (apo E) was investigated in seven type III hyperlipoproteinemic patients with the apo E-2/2 phenotype. Six of the patients had identical two-dimensional tryptic peptide maps. These differed from the normal apo E3 map by the altered mobility of a single peptide. Amino acid analysis and sequencing showed that apo E2 in these patients had a substitution of 158 Arg----Cys. The presence of this mutation in six of the seven type III patients confirms that this is the most common form of apo E2. The seventh type III patient had a unique map with a new peptide resulting from a substitution of 136 Arg----Ser. He was heterozygous for this and for the more common apo E2 (158 Arg----Cys) variant. His very low-density lipoprotein contained approximately five times more apo E2 (136 Arg----Ser) than apo E2 (158 Arg----Cys), as determined by cysteamine treatment and peptide mapping. This new apo E2 mutant thus appears to contribute significantly to the patient's hyperlipidemia.

Adult↗
PubMed1986

Familial type V hyperlipoproteinaemia in identical twins homozygous for apoliprotein variant E2: report.

Hyperchylomicronaemia and elevated very low density lipoproteins were found in relatively obese 47 year old identical twin brothers. Lipoprotein apoprotein studies showed the presence of apoprotein CII, the activator of lipoprotein lipase, and both men were homozygous E2/2. Studies on the ability of the brothers to clear triglyceride rich particles showed some impairment of post heparin lipase activity, and a slower clearance of infused fat emulsion. The values improved after weight loss. There was some evidence of impaired capacity of the patients' high density lipoprotein to activate post heparin lipoprotein lipase.

Apolipoprotein E2↗
PubMed1986

Trends in blood lead levels in Christchurch (NZ) and environs 1978-85.

Blood lead levels have been monitored since 1974 and have shown a significant decrease (p less than 0.001) from 1978 to 1985 in 2830 subjects from Christchurch and environs. From a baseline in August 1978-81 to August 1985 blood lead levels in a population which had no relevant exposure to lead other than that from the general environment have fallen in adult males and females (greater than 17 years) by 42%, and in school and pre-school children greater than 9 months by 44% and 46% respectively. Reduction of blood lead has accelerated during the last three years. This can be linked to changes in dietary intake and clean up of lead in domestic and industrial environments. Over this decade the lead content of petrol (0.84 g/l) and petrol sales have remained unchanged.

Adolescent↗
PubMed1985

Smoking, lung function, and alpha 1-antitrypsin deficiency.

From 1970 to 1983, 69 individuals (aged from infancy to 87 years) with homozygous alpha 1-antitrypsin deficiency (ZZ) were followed up. 12 had liver disease. Amongst the 33 patients with emphysema mean age of onset of dyspnoea in smokers (32 years) was significantly lower than that in non-smokers (51 years). Mean age at death (excluding that from liver disease) was 48 years in smokers and 67 in non-smokers. In non-smokers mean FEV1 was 77% of that predicted, but in smokers it was only 38% of that predicted. In non-smokers, FEV1 declined with age, but there was considerable individual variation. In smokers, the decline correlated with the extent of cigarette smoking in pack years. Mean decrease in FEV1 in non-smokers was abnormally high (80 ml/year), but significantly less than the massive mean decline of 317 ml/year in smokers. In ex-smokers the mean rate of decrease was 61 ml/year.

Adult↗
PubMed1985

Vesicoureteric reflux: segregation analysis.

Complex segregation analysis was applied to data from 88 families containing at least one person with vesicoureteric reflux. Analysis showed that a single major locus was the most important causal factor in this condition, with the mutant allele being dominant to the normal allele and having a gene frequency of about 0.16%. Forty-five percent of gene carriers will have vesicoureteric reflux and/or reflux nephropathy as adults and 15% will develop renal failure, compared to 0.05% and 0.001%, respectively, for those not carrying the gene. This analysis confirms the importance of screening close relatives of persons with proven vesicoureteric reflux or reflux nephropathy.

Adolescent↗
PubMed1985

Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment.

Apolipoprotein E phenotypes were determined on 417 consecutive lipid clinic patients using an isoelectric focussing technique. Of the 15 patients with phenotype E2/2, 13 (3.1%) had type III hyperlipoproteinaemia and 2 obese identical twins had type V. A further 20 patients (4.8%) had similar plasma and lipoprotein lipid levels but were E2 heterozygotes (14 E3/2 and 6 E4/2). They displayed a widened pre-beta-band almost confluent with the beta-band rather than the broad beta-band shown in classical E2/2 type III patients. In view of the similarities between these heterozygotes and the classical homozygous (E2/2) type III patients and their occurrence in the same families we suggest the nomenclature homozygous and heterozygous type III. In a subsequent comparison between 30 E2/2, 22 E3/2 and 8 E4/2 type III individuals the only significant difference in plasma and lipoprotein lipid parameters was a lower VLDL cholesterol to triglyceride ratio of 0.85 in E3/2 patients than that of 1.24 in E2/2 patients (P less than 0.01). Both homozygous and heterozygous patients showed premature ischaemic heart disease and both responded dramatically and similarly to treatment with clofibrate. These observations indicate that apo E phenotyping is worthwhile in all patients with combined hyperlipidaemia and that homozygous and heterozygous type III hyperlipoproteinaemia is not uncommon.

Adult↗
PubMed1984

Industrial lead exposure: a review of blood lead levels in South Island industries, 1974-83.

Relative risks of increased lead absorption found in 31 occupations were investigated. Serial red cell lead measurements on 1319 males and 186 females provided a mean and range for each occupational type. The magnitude of the mean and percentage of raised levels identified the degree of occupational risk. The mean red cell lead for 50% of employees was within the regional usual range for those not occupationally exposed. In 77% the mean red cell lead was less than 4.1 mumol/l. Of the remainder, 4% had levels greater than 5.7 mumol/l and 1% had levels greater than 7.7 mumol/l. Our findings have been used to manage local chronic and acute lead problems.

Erythrocytes↗