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Biomedical subjects

C Ericson

Publications and source records attributed to C Ericson.

At least 19 recordsLinked to original sources

Capillary and rotating-tube isoelectric focusing of a transmembrane protein, the human red cell glucose transporter.

The human red cell glucose transporter (Glut1) is a transmembrane protein. Monomeric Glut1 was purified by ion-exchange chromatography in the presence of the non-ionic detergent n-dodecyl octaoxyethylene (C12E8). For focusing, the ionic strength of the solution of C12E8-Glut1 complexes with co-purified lipids was lowered by dialysis, the detergent concentration was increased and carrier ampholytes were added. Focusing was done for 5 min at 3000 V in a methyl cellulose-coated glass capillary (50 microns I.D.). The anolyte H3PO4 was then replaced by NaOH for mobilization towards the anode. Absorbance monitoring at 280 nm showed two groups of zones at pH 6 and 8. Similarly, isoelectric focusing in a rotating quartz tube (3 mm I.D.) gave Glut1 zones at pH 5.5 and 8.0. Phosphorus analysis revealed that the Glut1 zone at pH 8 contained more phospholipids than did the other one. The above results together with previously determined and calculated isoelectric points (pI) of Glut1 indicate that the Glut1 at pH 8 is monomeric and that the zone at pH 5.5-6 represents oligomeric materials. The pI 8.0 at 22 degrees C applies for monomeric Glut1 in the absence of urea. The results exemplify that capillary isoelectric focusing of hydrophobic membrane proteins is possible.

Chromatography, Ion Exchange

Genetic and environmental determinants of cholesterol and HDL-cholesterol concentrations in blood.

Serum cholesterol and HDL-cholesterol have been studied in 274 Swedish nuclear families. The families were ascertained through the Swedish twin registry and consisted of married mono- and dizygous twins, their spouses and with at least one adult child. Total cholesterol was determined using an enzymatic colorimetric method and HDL-cholesterol by the heparin-manganese chloride precipitation method. The genetic analysis was performed using a path analytic model to resolve genetic and cultural heritability, marital correlations and maternal effects. Genetic heritability was 0.50 and 0.37 for total cholesterol and HDL-cholesterol, respectively. Cultural heritability was small, 0.04, for cholesterol but substantial 0.22, for HDL-cholesterol. A maternal effect was evident for cultural inheritance for HDL-cholesterol but not for cholesterol.

Adult

The effect of Gemfibrozil on human serum apolipoproteins and on serum reserve cholesterol binding capacity (SRCBC).

The lipid lowering drug Gemfibrozil significantly increased the levels of HDL-apoproteins, apoA-I and apoA-II in a group of 20 Swedish hyperlipemic males who were given 1200 mg daily of the drug for 8 weeks and thereafter submitted to a 4 weeks placebo period. It strikingly increased serum reserve cholesterol in binding capacity (SRCBC). No change was observed in "free" apoA-I or inthe level of Lp(a) lipoprotein. The results suggest that the effect of Gemfibrozil on HDL, may be particularly striking on a subclass (or on subclasses) of HDL responsible for most of SRCBC. The findings suggest that Gemfibrozil may become a useful drug for hyperlipidemic people, if its safety in pharmacological doses can be established.

Apolipoproteins

Effect of gemfibrozil on serum lipid levels.

A short term investigation of the effect of Gemfibrozil in 1200 mg daily doses has been carried out in a group of 20 Swedish males, 9 Lp[a+] and 11 Lp[a-]. The effect of 8 weeks of treatment upon serum lipids resembled those found in previous trials, with a significant decrease in serum total cholesterol. In this series, even VLDL cholesterol and apoB levels decreased significantly. With the apparent exception of HDL cholesterol, there was no suggestion that Lp[a+] individuals responded less well to treatment than did Lp[a-] individuals.

Cholesterol

In vitro studies of the interaction of isolated Lp(a) lipoprotein and other serum lipoproteins with glycosaminoglycans.

The interaction of isolated Lp(a) lipoprotein or other lipoprotein classes with different glycosaminoglycans (GAG) bound to activated Sepharose was studied. In contrast to LDL, the Lp(a) lipoprotein did not bind to the GAG tested if sodium was used as a buffer cation. In the presence of Ca++, however, even the Lp(a) lipoprotein was bound to GAG. This type of binding, probably mediated by divalent cation bridges, is apparently not a simple function of the GAG used. Addition of GAG in solution revealed that this binding may be the only one existing under physiological conditions, and it appears possible that the Lp(a) lipoprotein is bound more firmly to GAG than is LDL under such conditions.

Calcium

In vitro studies of the interaction of calcium ions and other divalent cations with the Lp(a) lipoprotein and other isolated serum lipoproteins.

The interaction of isolated Lp(a) lipoprotein with different divalent cations was studied and compared to that of other isolated lipoprotein classes. Purified Lp(a) lipoprotein was found to be most sensitive to the metal ions tested, and the Lp(a) lipoprotein was the only lipoprotein which was precipitated by calcium ions alone. The precipitation apparently depends on the ionic radii of the cations used as well as on the lipoprotein class tested. The precipitation reaction between calcium ions and the Lp(a) lipoprotein, and the interaction between calcium ions and LDL (without precipitation) seem to follow the known rules for small ion-macromolecule interaction reasonably well. The calcium ion - Lp(a) lipoprotein interaction results in a small aggregate. The binding is of ionic type and the precipitation reaction is initially reversible. It was estimated that LDL particles have a mean of 290 equivalent and non-interacting binding sites for calcium ions. The above observations concerning the Lp(a) lipoprotein may be of interest in view of the significantly higher frequency of early coronary heart disease in Lp(a+) than in Lp(a-) individuals, and in view of the previously reported biochemical differences between individuals of different Lp phenotype.

Calcium

Interaction of isolated Lp(a) lipoprotein with calcium ions and glycosaminoglycans in vitro.

The interaction between the lipoprotein carrying the Lp(a) antigen, i.e. the Lp(a) lipoprotein, and agarose gels substituted with glycosaminoglycans, as well as the precipitation of the Lp(a) lipoprotein by Ca++ were studied. Comparisons between Lp(a) lipoprotein and other serum lipoproteins were conducted. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were bound to the tested glycosaminoglycans at low ionic strength of sodium chloride, but no binding was found with the Lp(a) lipoprotein. However, Ca++ as a divalent buffer cation gave a precipitating Ca++-Lp(a) lipoprotein complex even at a physiological Ca++ concentration. VLDL and LDL were not precipitated under these conditions. These findings may be of interest in relation to the previously reported higher frequency of the phenotype Lp(a+) in subjects with coronary heart disease.

Agar

Co-trimoxazole in the long-term treatment of pyelonephritis with normal and impaired renal function.

The effect of co-trimoxazole was studied in 29 cases of acute or chronic pyelonephritis. The therapy produced the desired effect in 22 out of 23 cases and in the 6 cases treated prophylactically. We used a special dosage schedule for the combination of sulphamethoxazole and trimethoprim in the treatment of patients with normal renal function and with varying degrees of renal impairment. The results show that the plasma concentrations were at satisfactory therapeutic levels, with no accumulation of the three substances and without causing any toxic side effects, even in patients with severe impairment of the renal function. The mean duration of the treatment was 12.3 months. The material is, however, not largelu enough to warrant the recommendation of standardized treatment according to the schedule described, in spite of the favourable experience gained. It does, however, permit us to recommend that the plasma concentrations should be determined, particularly of the total sulphamethoxazole in patients with severely impaired renal function.

Acute Disease

Lp(alpha) lipoprotein and pre-beta1-lipoprotein in relation to lipid levels in males.

Previous studies have shown that a slow-moving pre-beta-lipoprotein fraction, named the pre-beta1-lipoprotein, occurred significantly more frequently among subjects with coronary heart disease (CHD) than among healthy individuals. This lipoprotein is closely related to, and probably identical with, the Lp(a) lipoprotein. Immunological tests likewise showed that Lp(a) lipoprotein was significantly more common among patients with CHD than among controls. Mean cholesterol and triglyceride levels were higher in pre-beta1-lipoprotein positive than in pre-beta1-lipoprotein negative individuals. Lp(a+) individuals tended to have higher serum cholesterol values than did Lp(a-) persons but there was no difference in the mean triglyceride value. This apparent discrepancy seems to be due to the presence in occasional sera of lipoprotein fractions with pre-beta1-mobility, usually of a VLDL nature. These lipoproteins are not associated with the Lp(a) lipoprotein.

Antigens

Lp(a) lipoprotein/pre-beta1-lipoprotein in Swedish middle-aged males and in patients with coronary heart disease.

A strong, positive association (P smaller than 0.0001) was found between the presence in serum of pre-beta1-lipoprotein upon electrophoresis in 0.5% agarose and the Lp(a+) phenotype in a series of 103 males aged 50-52 years participating in a health control study and in a series of 58 patients with sustained myocardial infarction. Both lipiprotein phenomena were more prevalent in the 58 patients than in the 103 presumably healthy males. The lack of any significant difference between total cholesterol values in the patients and the controls, despite the higher frequency of phenotype Lp(a+) in the former group, argues against the suggestion by Walton et al. (1974) that the increased Lp(a+) frequency in patients with coronary artery disease may be caused by a general increase in the concentration of low density lipoproteins (LDL).

Cholesterol

Bacteremia: the significance of outside versus inside hospital origin.

168 patients with bacteremia seen in 1965-1969 were studied with regard to mortality rate, age and sex distribution, sources of infection, predisposing factors and infecting organisms. Special attention was drawn to outside hospital originating bacteremia vis-a-vis hospital-acquired bacteremia. In general, the results obtained were essentially in agreement with earlier experiences elsewhere. The most striking observations were, firstly, the grave prognosis associated with hospital-acquired bacteremia and, secondly, the dominant role played by gram-negative bacilli.

Adolescent