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Biomedical subjects

H Eriksson

Publications and source records attributed to H Eriksson.

At least 145 records · Page 8Linked to original sources

Spontaneous association of purified major histocompatibility class I antigens with recipient cells after removal of detergent.

Affinity chromatography purified major histocompatibility class I antigens (MHC class I) from rat (RT-1) and mouse (H-2) became spontaneously associated with human lymphocytes after removal of the non-ionic detergent Triton X-100 by adsorption to Biobeads SM-2. No increased cell death was observed immediately after association with the new MHC class I antigen. However, after 20 h at 37 degrees C, cells with transferred antigen showed a lower viability than untreated cells. Long-time survival of the recipient cells improved if the MHC class I antigens were incorporated into liposomes. Lipids of differing compositions were investigated and the best long-term cell survival and the highest levels of transferred antigen were obtained with phosphatidylcholine liposomes. The transferred antigen exhibited time- and temperature-dependent removal from the cell surface and complement-mediated lysis of the cells indicated that some of the antigen was introduced into the membrane of the recipient cells.

Animals↗

A carbohydrate epitope associated with human squamous lung cancer.

A monoclonal antibody, 43-9F, specifically recognizes a tumor-associated antigen expressed both on surface membrane glycoproteins and on secreted soluble mucins of human squamous lung carcinoma (SLC) cells, and the corresponding antigen can be detected as a circulating tumor marker in plasma of SLC patients. Thin-layer chromatography immunostaining of neutral glycolipids extracted from SLC cells reveals a 43-9F-reactive glycolipid whose carbohydrate structure, as determined by fast atom bombardment-mass spectrometry, is identical with that of an Lea-active pentaglycosylceramide described previously: Gal beta 1-3[Fuc alpha 1-4]-GlcNAc beta 1-3Gal beta 1-4Glc-Cer. However, the Lea-active oligosaccharide hapten, lacto-N-fucopentaose II, with the same carbohydrate structure, fails to inhibit binding of 43-9F, and a well-characterized anti-Lea monoclonal antibody blocks only 40% of 43-9F binding sites on SLC cells, suggesting that the major epitope recognized by 43-9F is more complex than the Lea epitope. To search for a higher affinity 43-9F epitope among more complex oligosaccharides, a mixture of tritiated neutral oligosaccharide alditols from pooled human milk was passed through a 43-9F affinity column. A major retarded oligosaccharide was purified by high-performance liquid chromatography and shown by fast atom bombardment-mass spectrometry to have the following structure: Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal beta 1-4[Fuc alpha 1-3] GlcNAc beta 1-3Gal beta 1-4Glc. Oligosaccharides containing this sugar sequence are at least 100-fold more active than lacto-N-fucopentaose II as competitive inhibitors of 43-9F. Thus, antibody 43-9F binds to the above difucosyl Lea-X determinant with high affinity and weakly cross-reacts with the Lea antigen under some conditions such as occurs in thin-layer chromatography and enzyme-linked immunosorbent assay where multiple weak interactions of the decavalent IgM antibody may occur.

Antibodies, Monoclonal↗

The use of a fluorescent lipid as a non-covalent bound tracer of integral membrane proteins.

Solubilized and affinity purified major histocompatibility class I and class II antigens (MHC-I, MHC-II) were incorporated into liposomes, which contained a fluorescent lipid, by adsorption of the detergent to Biobeads SM-2. The fluorescent lipid was used as a non-covalently bound tracer to detect antibody-mediated agglutination of liposomes with MHC antigens. After incorporation of the membrane proteins into liposomes of different lipid composition, phosphatidylcholine was chosen as a lipid matrix. The use of a fluorescent lipid as a tracer of membrane proteins was demonstrated by the detection of human beta 2-microglobulin association with mouse MHC-I. Furthermore the method was used to measure the amount of liposomes containing two different membrane proteins.

Chemical Precipitation↗

Risk factors for type 2 (non-insulin-dependent) diabetes mellitus. Thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913.

This report presents data on antecedents of Type 2 (non-insulin-dependent) diabetes mellitus in a homogeneous sample of randomly selected 54-year-old men from an urban Swedish population with a diabetes incidence of 6.1% during 13.5 years of follow-up. The increased risk leading to diabetes for those in the top quintile compared to the lowest quintile of the distribution of statistically significant risk factors were: body mass index = 21.7, triglycerides = 13.5, waist-to-hip circumference ratio = 9.6, diastolic blood pressure = 6.7, uric acid = 5.8, glutamic pyruvic transaminase = 3.9, bilirubin = 3.2, blood glucose = 2.7, lactate = 2.4 and glutamic oxaloacetic transaminase = 2.0. Those with a positive family history of diabetes had 2.4-fold higher risk for developing diabetes than those without such a history. In a multivariate analysis glutamic pyruvic transaminase, blood glucose, body mass index, bilirubin, systolic blood pressure, uric acid and a family history of diabetes were all significantly associated with the development of diabetes. Our study demonstrates the great importance of adiposity and body fat distribution for the risk of diabetes. A number of established risk factors for coronary heart disease are risk factors for diabetes as well. Disturbed liver function and increased levels of lactate are early risk factors for diabetes - presumably indicators of the presence of impaired glucose tolerance and/or hyperinsulinaemia.

Alanine Transaminase↗

Musculo-skeletal symptoms as related to working conditions among Swedish professional fisherman.

The present study has confirmed the concern of previous investigators that professional fishing is a strenuous occupation. We have been able to show that complaints of symptoms from the musculo-skeletal system are common, and that they follow a logical pattern in terms of the influence of a few key parameters, such as age, number of years in the fishing trade, type of fishing and type of working tasks on board. There is reason to believe that these findings provide a sound basis for action-oriented research and a development programme focusing on reducing the risk of fishermen acquiring chronic chronic disorders of the musculo-skeletal system. In a subsequent article we shall present such a programme, which has been carried out for the Swedish fishery.

Journal Article↗

Workload and ergonomics measures in Swedish professional fishing.

The major types of professional coastal fishery in Sweden were studied. A questionnaire indicated that symptoms from the musculo-skeletal system were common and that certain symptoms related to certain types of fishing. Working tasks inducing severe workload were identified. They concerned handling the fishing gear as well as handling the catch. Ergonomics measures to decrease the workload were suggested and evaluated through ergonomics assessment, measurements of oxygen uptake and working posture analyses. It was found that ergonomics measures can be taken which are efficient in reducing the load on the musculo-skeletal system of the fishermen.

Journal Article↗

Evidence for a direct effect of thyroid hormones on the hepatic synthesis of estrogen receptors in the rat.

The role of thyroid hormones in the regulation of estrogen receptor turnover in the rat liver was studied. Animals subjected to thyroidectomy or hypophysectomy in combination with different hormone substitutions, were used. The receptor level in control animals was 53 fmol/mg cytosol protein. Thyroidectomy for 28 days caused a dramatic reduction to 20 fmol/mg, whereas hypophysectomy for 9 days resulted in an even more substantial reduction to 11 fmol/mg protein. If animals, hypophysectomized for 9 days, were given triiodothyronine (T3) for 9 days the hepatic estrogen receptor concentration was elevated to 22.5 fmol/mg protein. Estradiol given together with T3 did not cause any further increase in the receptor level. We conclude that thyroid hormones affect the hepatic synthesis of estrogen receptors on two levels, via a direct action on the liver and via an indirect modulation of the pituitary hormone synthesis/release.

Animals↗

Early heart failure in the population. The study of men born in 1913.

A cross-sectional analysis of characteristics possibly associated with congestive heart failure (CHF) was performed among 644 men, all 67 years of age and randomly selected from the general population. A total of 13% had symptoms and signs of overt CHF. Another 10% had early or "latent" CHF. Among overt CHF cases, 46% had hypertension, 55% coronary heart disease and 79% any one of these conditions. Among "latent" CHF cases, the corresponding proportions were 52%, 25% and 65%. Simple indices of left ventricular diastolic function and filling pressure as well as of pulmonary artery pressure were closer related to the CHF stage, than were measures of systolic left ventricular function. Smoking habits, hypertension, blood lipids, weight and other measures of body fat, blood glucose, and serum insulin were all correlated to CHF stage. In a multivariate analysis, smoking habits, hypertension, body weight, and serum insulin were independently and significantly correlated to CHF stage.

Aged↗

Dyspnoea of cardiac origin in 67 year old men: (1). Relation to systolic left ventricular function and wall stress. The study of men born in 1913.

The relation between dyspnoea of presumed cardiac origin and disturbed left ventricular systolic function was studied in a group of 67 year old men from the general population of Gothenburg, Sweden. Forty two men with cardiac dyspnoea were identified and 45 controls were randomly selected from a screened cohort of 644 men. Dyspnoea was graded according to the World Health Organisation standard, and M mode echocardiography, carotid pulse tracing, an apex cardiogram, and phonocardiography were used to evaluate the grade of dyspnoea and its relation to systolic time intervals, left ventricular ejection indices, and wall stress. The dyspnoea grade was significantly related to the left ventricular end systolic dimension, to septal and posterior wall fractional thickening, and to ejection indices such as fractional shortening. The dyspnoea grade was also significantly correlated with the ratio of end systolic wall stress to end systolic volume index. There was a close relation between end systolic wall stress and mean velocity of circumferential fibre shortening adjusted for heart rate. This relation did not clearly show reduced inotropy in the dyspnoeic men. There was no relation between the degree of dyspnoea and the systolic time intervals. Among the systolic variables obtained by echocardiography the only abnormal finding in mild to moderate dyspnoea was an increased end systolic dimension. The grade of cardiac dyspnoea seemed to be related to the degree of systolic left ventricular dysfunction, which was considerably impaired in severe dyspnoea. In population studies left ventricular end systolic dimension and fractional shortening may provide sufficient information on systolic function without the need to assess variables that are independent of load.

Aged↗

Dyspnoea of cardiac origin in 67 year old men: (2). Relation to diastolic left ventricular function and mass. The study of men born in 1913.

The relation of cardiac dyspnoea to diastolic left ventricular dysfunction was examined in a sample of 67 year old men from the general population of Gothenburg, Sweden. Forty two men with cardiac dyspnoea and 45 controls were selected from the screened cohort of 644 men. M mode echocardiography, apexcardiography, and phonocardiography were used to evaluate heart sounds, diastolic time intervals, aortic root motion (atrial emptying index); peak rate of change in left ventricular dimension, left atrial and ventricular size; and left ventricular mass. There was a significant relation between dyspnoea grade and left ventricular mass and posterior wall thickness. Dyspnoea grade also correlated significantly with the amplitude of the rapid filling wave and the third heart sound, atrial emptying index and left atrial size, the pulmonary component of the second heart sound, and the dimension of the right ventricle. In mild to moderate dyspnoea fractional shortening was normal, but posterior wall thickness and left atrial dimension were increased. The time from the second heart sound to the O point of the apexcardiogram, adjusted for heart rate, was significantly prolonged in mild to moderate dyspnoea, but not in severe dyspnoea. There was a significant decrease of rate adjusted isovolumic relaxation time, probably secondary to altered loading conditions, in severe dyspnoea, but not in mild to moderate dyspnoea. When the effect of systolic function was excluded multivariate analyses showed that the relation between dyspnoea grade and left atrial dimension persisted. The finding that diastolic abnormalities of the heart contributed to the generation of cardiac dyspnoea may have implications for treatment.

Aged↗

The diurnal variation of serum hyaluronan in health and disease.

The variation of the serum concentration of hyaluronan during the day and between days has been investigated. In a group of healthy volunteers, the mean hyaluronan level was very stable over time except for a moderate but significant elevation after rising from bed in the morning. Patients with rheumatoid arthritis showed markedly increased hyaluronan concentrations 0.5-2 h after leaving bed. Patients with primary biliary cirrhosis exhibited high and rather constant levels during the day. A reference group of hospitalized patients with other diseases did not show any diurnal variation. The best reproducibility in hyaluronan determinations is obtained if specimens are taken before the subjects rise from bed or a few hours later, i.e. after the morning elevation of serum hyaluronan has subsided. In rheumatoid arthritis valuable information can be obtained by repeated sampling during the morning hours.

Adult↗

Quality of life in early heart failure. The study of men born in 1913.

To see whether well-being and quality-of-life are affected in congestive heart failure (CHF), a number of health variables, self-assessed and objectively measured, were estimated among 67-year-old men sampled from the general population of Gothenburg, Sweden. Based on history, physical examination and drug treatment, 407 men were studied and grouped into 4 stages of CHF, ranging from no signs or symptoms of CHF to advanced CHF. Men with CHF had more of other cardiovascular disease manifestations, utilized more health care, and reported less well-being and a higher rate of self-assessed disability than men with no CHF. These quality-of-life changes were found not only in the overt cases but also in early CHF. Regardless of CHF stage, quality-of-life seemed more affected in men on drug treatment, compared with those not treated.

Clinical Protocols↗

Association between expression of a tumor-associated carbohydrate epitope and the proliferative and tumorigenic activity of a human squamous lung cancer cell line and epitope-positive and -negative sublines.

A previously described epitope (designated 43-9F) with high specificity for human squamous carcinoma and adenocarcinoma of the lung is here reported to be associated with the proliferative and tumorigenic activity of a cloned human squamous lung carcinoma (SLC) cell line (SLC-L11) and a number of cloned sublines. Lines with appreciable 43-9F epitope density (43-9F+) had a short population doubling time and were tumorigenic in athymic nude mice, whereas clones with low 43-9F epitope density (43-9F-) of the same line had longer population doubling times and did not result in 43-9F- tumors in athymic nude mice. Some of the 43-9F- clones reverted to the 43-9F+ phenotype and then became tumorigenic. Two other SLC lines (SLC-L12 and SLC-L13), positive and negative, respectively, for 43-9F also expressed tumorigenic and proliferative behavior concordant with the data for SLC-L11 and its sublines. Cell lines of human squamous cell carcinomas had a pronounced intratumoral heterogeneity in respect to 43-9F epitope expression. Fluorescence-activated cell sorting of cells with high and low 43-9F density and subsequent cloning demonstrated that the cloning capacity was confined almost exclusively to cells with high antigen density. Immunoaffinity chromatography and gel filtration showed that the epitope was expressed in glycoproteins with molecular weights in the range of 5 X 10(6)-5 X 10(4). Mild alkaline hydrolysis reduced the binding of 43-9F antibody to SLC-glycoproteins while neuraminidase treatment augmented the 43-9F antibody binding. It is concluded that expression of 43-9F+ glycoproteins seems linked to the proliferative and tumorigenic features of human squamous lung carcinoma cell lines.

Animals↗

Relation of dyspnea to left ventricular wall motion disturbances in a population of 67-year-old men.

Dyspnea, a potential early symptom of coronary artery disease and congestive heart failure, was evaluated to establish its relation to left ventricular wall motion abnormalities. A group of 67-year-old men, drawn from the general population of Gothenburg, Sweden, was studied. Acceptable studies by 2-dimensional echocardiography were obtained from 42 of 49 men with dyspnea of presumed cardiac origin, and from 45 randomly selected nondyspneic control subjects. Both groups originated from a random population sample of 644 men. All men with akinesia, not limited to the basal inferolateral segment, were dyspneic. Akinesia (inferolateral segment only) was found in 4 of 45 control subjects (9%). Six of 20 men (30%) with low-grade dyspnea and 5 of 5 men with the most severe grade of dyspnea had 1 or more akinetic segments. The severity of dyspnea was related to regional wall motion disturbances (as classified in 11 anatomic segments [p less than 0.02 to p less than 0.0001]) and to presence and number of akinetic segments (p less than 0.0001). The degree of dyspnea was correlated to anterior (p less than 0.0001) but not inferior akinesia. The regional wall motion disturbances measured by echocardiography still contributed significantly to the explanation of dyspnea when taking into account the presence or absence of clinical coronary artery disease determined from a 12-lead electrocardiogram, the history of angina pectoris and myocardial infarction, and the findings on chest x-ray films. Thus, presumed cardiac dyspnea is a sensitive marker of regional wall motion disturbances. Furthermore, the location of these disturbances may be of importance for the hemodynamic changes leading to cardiac dyspnea.

Aged↗

Forskolin blocks carbachol-mediated ion-permeability of chick myotube nicotinic receptors and inhibits binding of 3H-phencyclidine to Torpedo microsac nicotinic receptors.

Forskolin, a commonly used adenylate cyclase activator, was found to inhibit reversibly the carbachol-induced ion-translocating capacity of the nicotinic acetylcholine receptor (nAChR) on chick myotubes in a dose- (IC50 = 20 microM) and time-dependent manner. This effect was not correlated to increases in cellular cAMP. Forskolin, at a concentration (50 microM) that totally blocked the carbachol-induced 86Rb influx, caused no change in carbachol or alpha-bungarotoxin binding to chick myotube nAChR in situ. In contrast, in the presence of carbachol, forskolin inhibited (IC50 = 10 microM) the binding of 3H-phencyclidine, a putative nAChR ion-channel ligand, to Torpedo microsac nAChR. Inhibition of 3H-phencyclidine binding in the absence of carbachol was not complete. Membrane leakage studies on myotubes, measuring 3H-efflux from 2-deoxy-D(1-3H)-glucose loaded cells and electrophysiological measurements of membrane properties supported the interpretation that forskolin induced decreases in plasma membrane permeability. In conclusion, forskolin blocks the carbachol-mediated increase in permeability of the nAChR channel by (1) binding to the ion-channel (open state) and (2) generally perturbing the plasma membrane function possibly by interfering with the protein-lipid interface.

Animals↗