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Biomedical subjects

S Johansson

Publications and source records attributed to S Johansson.

At least 199 records · Page 11Linked to original sources
PubMed1989

Uptake and degradation in vivo and in vitro of laminin and nidogen by rat liver cells.

Laminin antigens are known to be present in the blood of normal individuals. In the present study we have investigated the fate of laminin-related molecules in the circulation. After intravenous injection in rats, the native laminin-nidogen complex, as well as the separated proteins, were rapidly eliminated from the blood (half-lives 2-10 min) by the liver. The large laminin fragments E1 and E8 (Mr 400,000 and 280,000 respectively), which contain the major cell-adhesion-promoting activities of laminin, were also cleared from the blood mainly by the liver, but the rate of uptake was an order of magnitude lower for these fragments than for laminin. This indicates that the uptake of laminin did not occur via cell-adhesion receptors. The endothelial cells of liver were the most important cell type in the uptake of laminin-nidogen complex, nidogen, laminin and fragment E1, whereas the parenchymal cells were responsible for more than 50% of the uptake of E8 in the liver. Studies in vitro with cultured liver endothelial cells and parenchymal cells demonstrated that the ligands were endocytosed and degraded independently of plasma factors. The results reveal that the level of laminin antigens in blood is a very complex parameter. It is not only dependent on the turnover of basement membranes, but also on the degree of degradation of the material released into the blood and on the functional state of the liver, particularly the liver endothelial cells.

Animals↗
PubMed1989

A substrate of the cell-attachment sequence of fibronectin (Arg-Gly-Asp-Ser) is sufficient to promote transition of arterial smooth muscle cells from a contractile to a synthetic phenotype.

Extracellular matrix components strongly influence the differentiated properties of isolated rat arterial smooth muscle cells during in vitro cultivation. The attachment and spreading of the cells on a substrate of fibronectin or a 105-kDa cell-binding fragment of fibronectin are accompanied by a structural and functional transformation, referred to as a transition or modulation from a contractile to a synthetic phenotype. Here, the ability of the cell-attachment sequence of fibronectin, Arg-Gly-Asp-Ser (RGDS), to promote this process was studied. The results demonstrate that freshly isolated smooth muscle cells attached to a substrate of the synthetic peptide Gly-Arg-Gly-Asp-Ser-Cys (GRGDSC) in a specific manner and as well as to substrates of fibronectin and the 105-kDa fragment. Subsequent spreading of the cells on the peptide substrate followed the same kinetics and was as extensive as on fibronectin, even if protein synthesis was blocked by treatment of the cultures with cycloheximide. Like fibronectin, the peptide substrate induced formation of actin filament bundles, again without ongoing protein synthesis. Moreover, it was as efficient as fibronectin in supporting the transition of the cells from a contractile to a synthetic phenotype as analyzed by electron microscopy. Antibodies against the beta subunit of the fibronectin receptor interfered with the attachment, spreading, and fine structural reorganization of the cells in a similar manner on substrates of fibronectin, the 105-kDa fragment, and GRGDSC. Taken together, the findings indicate that the cell-attachment sequence (RGDS) mimics intact fibronectin in promoting a change in the differentiated properties of arterial smooth muscle cells and does so by interacting with a cell surface receptor for fibronectin.

Actins↗
PubMed1989

Lack of correlation between the apolipoprotein B XbaI polymorphism and blood lipid levels in a Swedish population.

The possible connections between the apolipoprotein B (apo B) XbaI polymorphism and the serum levels of total cholesterol, triglycerides, LDL, HDL and apo B have been investigated among 187 randomly selected subjects from Gothenburg, Sweden. The interferences of age and sex on the serum lipoproteins and apo B concentrations were considered. Using multiple regression analysis, we compared the different lipid levels and the levels of apo B with the genotypes X1X1, X1X2 and X2X2 (X1 = without the XbaI restriction site, X2 = with the site), with age and with sex and with those factors combined with each other. A significantly higher concentration of serum cholesterol and LDL among men than among women was found and total serum cholesterol, LDL and apo B were positively correlated with age. The allele frequency of the XbaI polymorphism in the sample was 0.45 for the allele without the XbaI restriction site. No correlation was found between the apo B genotypes and the levels of serum lipoproteins or apo B.

Adult↗
PubMed1989

Characterisation of a secreted form of recombinant derived human growth hormone, expressed in Escherichia coli cells.

Recombinant DNA derived human growth hormone (rhGH), Genotropin, has been expressed in E. coli cells as a pre-hormone, where the heat stable enterotoxin II signal peptide (STII) was linked to hGH to get secretion of the hormone to the periplasmatic space. The pre-hormone was efficiently cleaved during secretion, by an endogenous signal peptidase generating the correct N-terminal (Phe) end as shown by protein sequence analysis. The purity of rhGH was studied by SDS-PAGE, in combination with laser densitometry and HI-HPLC. These techniques showed that the level of modified rhGH forms, e.g. aggregated and proteolytically cleaved (16 and 6 kDa) in the preparation was in the 0.5-1% range. Furthermore, evidence that the correct disulphide bonds (Cys53-Cys165; Cys182-Cys189) were formed in rhGH during secretion has been shown by a combination of tryptic fingerprint and amino acid analysis. CD-spectroscopic analysis suggested an identical secondary structure to that of pituitary derived human growth hormone (pit-hGH). Isoelectric focusing revealed an isoelectric point (pI) for rhGH of 5.0 similar to pit-hGH and in excellent agreement with the theoretical value 5.1, based on the primary sequence. Finally, an apparent molecular weight of 22,000 was obtained for rhGH, by SDS-PAGE. All these physico-chemical studies suggest that rhGH is structurally identical to pit-hGH, somatotropin.

Amino Acid Sequence↗
PubMed1989

Integrin-type fibronectin receptors of rat arterial smooth muscle cells: isolation, partial characterization and role in cytoskeletal organization and control of differentiated properties.

The spreading of freshly isolated rat arterial smooth muscle cells (SMCs) on a substrate of fibronectin (FN) is associated with marked changes in fine structure and function of the cells, collectively referred to as a modulation from a contractile to a synthetic phenotype. Recent studies have indicated that this process is mediated via an interaction between the minimal cell-attachment sequence of FN (RGDS) and cell surface receptors. Here, we report the isolation of such receptors by sequential chromatography on affinity columns of wheat germ agglutinin (WGA) and a 105-kDa cell-binding fragment of FN (105-kDa fragment). The receptor was composed of two proteins with electrophoretic mobilities in SDS-polyacrylamide gels of 160 and 115 kDa under nonreducing conditions and 150 and 130 kDa under reducing conditions. Immunoprecipitation of surface-labeled cells with a rabbit antiserum against the beta chain of the rat hepatocyte FN receptor similarly yielded two proteins of 160 and 115 kDa. In metabolically labeled cells an additional component of 105 kDa was precipitated, presumably representing a precursor of the 115-kDa protein. Immunocytochemical studies demonstrated that SMCs grown on laminin formed FN fibrils and actin filament bundles in close alignment with cell surface receptors after a few days of culture. In cells seeded on the 105-kDa fragment, the receptors were already arranged in parallel with actin filaments on the first day of culture. Later on, the cells secreted FN and laid down FN fibrils along the receptors on the cell surface and the actin filament bundles in the cytoplasm. Taken together, the findings indicate that arterial SMCs are equipped with FN receptors that belong to the integrin family of proteins and consists of alpha (160-kDa) and beta (115-kDa) subunits. The receptor complexes apparently play an important role in determining the differentiated characteristics of the cells, possibly by mediating a linkage between the extracellular matrix and the cytoskeleton.

Animals↗
PubMed1989

Action potentials of cultured human oat cells: whole-cell measurements with the patch-clamp technique.

Oat cells (of the small cell carcinoma of the lung) have been reported to generate calcium action potentials. The calcium channels have further been suggested to play a crucial role in the relation between oat cell carcinoma and the often associated myasthenic syndrome. We have examined cultured human oat cells (U-1690) under voltage-clamp conditions, using the patch-clamp technique. We found, contrary to previous reports, that the action potential was caused by sodium and potassium currents. No calcium current was detected under these conditions, which indicates that calcium channels, if present, are very rare. The findings restrict, but do not rule out, the hypothesis that calcium plays a key role in the carcinoma/myasthenic syndrome relation.

Action Potentials↗
PubMed1989

Effects of adrenaline and prior exercise on the release of alanine, glutamine and glutamate from incubated rat skeletal muscle.

Catecholamines have been proposed as important regulators of the rate of amino acid release from skeletal muscle. In the present study, we have investigated the influence of adrenergic action and its possible interaction with exercise on muscle release and tissue content of alanine, glutamine and glutamate. For this purpose epitrochlearis muscles were dissected from resting and exercised (1 and 2 h) rats and incubated for 1 h in the presence or absence of adrenaline. In addition, muscles from water-immersed resting rats were included to separate the influence of the stress involved in the swimming exercise from that of muscle contractile activity per se. In muscles from untreated resting rats, the release, tissue content and total amount (released amount + tissue content) of the three amino acids were not influenced by 10(-7) M adrenaline; when the adrenaline concentration was raised to 10(-5) M only the tissue content of glutamate was significantly changed (-50%, P less than 0.001). However, in muscles of rats subjected to 2 h prior exercise or water immersion, 10(-7) M adrenaline significantly increased the release of glutamine (+ 48% and +34%, P less than 0.05) and glutamate (+38% and +27%, P less than 0.05). Moreover, 1 h of water immersion resulted in a significant increase in muscle glutamine and glutamate compared to values from the exercised and control rats. The data suggest that adrenergic action is involved in the regulation of muscle amino acid transport during exercise and that the stress involved in exercise may mask the influence of contractile activity per se on formation of amino acids in skeletal muscle.

Alanine↗
PubMed1989

A model for the fast 4-aminopyridine effects on amphibian myelinated nerve fibres. A study based on voltage-clamp experiments.

The effect of 4-aminopyridine (4-AP) on the potassium currents in the node of Ranvier in myelinated nerve fibres was investigated with the voltage-clamp technique. The potential and time dependence of the currents in solutions with a high potassium concentration (114.5 mM) were studied. The block of the tail current was found to be less than that of the corresponding current during a potential step. Also, the time-course of the tail current was modified. In order to explain these findings, kinetic models of the 4-AP action were constructed and analysed numerically. A simple four-state model, in which 4-AP interacts only with open channels and where the binding is diphasically potential dependent, was found to account for the effects.

4-Aminopyridine↗
PubMed1989

Growth hormone regulates the rodent hepatic epidermal growth factor receptor at a pretranslational level.

Recent studies have implicated the involvement of pituitary factor(s) in the regulation of hepatic epidermal growth factor receptor (EGF-R) levels. In the present study the possible role of GH as a regulator of EGF-R has been examined by measuring hepatic EGF-R mRNA and EGF binding in intact and GH-deficient rats and mice before and after administration of GH. Using a human EGF-R probe, 10.5 and 6.0 kb transcripts were detected in mouse and rat liver by Northern gel analysis. EGF-R mRNA was quantified by solution hybridization, and EGF binding determined by incubation of 125I-labelled EGF with a low-density membrane fraction. Levels of hepatic EGF-R mRNA and binding of EGF in female rats were about two-thirds of those in male rats. GH-deficient (lit/lit) male and female mice had approximately 10 and 25% respectively of the levels of EGF-R mRNA and EGF binding of intact male and female mice. Furthermore, hypophysectomized rats exhibited a reduced level of EGF-R mRNA and EGF binding, corresponding to about 20% of the levels detected in intact male rats. When hypophysectomized male and female rats received recombinant human GH (hGH) either as intermittent injections or by continuous infusion using osmotic minipumps, the EGF-R mRNA and EGF binding levels increased to about half those of the intact male animals. No differences between intermittent or continuous administration of hGH on the induction of EGF-R mRNA or EGF binding could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A model for prediction of endometrial cancer.

An epidemiological statistical model was designed to identify women at low and high risk of developing endometrial cancer (EC). The model was based on a number of easily identified clinical factors such as hirsutism, parity, diabetes mellitus, body mass index (BMI) and smoking. A retrospectively collected series of 77 women aged 31 to 45 years with EC and a prospectively collected series of 122 women aged 43 to 70 years with EC were compared with 1409 controls. The participation frequencies in the two case materials were 83 and 87%, respectively. The series were examined by means of a questionnaire. In a stepwise multiple logistic regression analysis of the entire series the following variables were found to be significant; hirsutism, parity, BMI, diabetes mellitus and smoking.

Adult↗
PubMed1989

Longevity in women.

Cross-sectional and longitudinal studies on vital statistics and population-based samples document that women live longer than men. The sex mortality differential covers all ages and races in most developed nations. The magnitude of the sex mortality differential varies with age, being especially high at younger ages. The most important contributor to the difference in mortality between women and men is the major cause of death in men, i.e., cardiovascular diseases. The universality of the sex mortality differential in various geographical areas, the lower female infant mortality, and the possible hormonal-mediated relative protection of CHD in women all indicate that biological factors contribute to the lower mortality in women than in men. Secular changes in mortality of various diseases over short periods cannot be explained by innate endogenous alterations but instead have to be influenced by behavioral factors and other components of the environment. Longstanding biological differences between women and men might play a role in producing a relatively rapid emergence of sex mortality differential only by interaction with relatively new exogenous environmental factors. The vast majority of studies on the sex differential in mortality trends confirm the importance of smoking as a major contributor to the higher mortality in men than in women. Along this line, other behavioral factors also seem to influence longevity in women. With ongoing changes in society, especially increasing participation of women in the labor force, new components of the environmental setting will have to be assessed by comparable and identical instruments in different populations. Ongoing monitoring of trends in cardiovascular and noncommunicable diseases will provide valuable insight into the sex mortality differential and its determinants. Experimental studies on biological reactivity, sex endocrinology, and atherogenesis are also needed to help explain why women live longer than men.

Adult↗
PubMed1989

CHD in Sweden: mortality, incidence and risk factors over 20 years in Gothenburg.

Mortality from coronary heart disease (CHD) increased among Swedish men between 1968 and 1981, but after that, began to decline. CHD mortality in women decreased slightly, mostly among older women. From 1980, the incidence of non-fatal myocardial infarction (MI) started to decrease among men. Among middle-aged women, however, there was a significantly increased incidence. Mortality during the two years following hospital discharge decreased both in men and women between 1968 and 1985 in Gothenburg. Between one-sixth and one-fifth of major CHD events occur among patients with previous MI or angina pectoris. Serum cholesterol and smoking habits increased among middle-aged men from 1963 to 1973, but decreased thereafter. Blood pressure decreased, and the percentage of people on treatment increased. Blood pressure and serum cholesterol decreased among middle-aged women, but smoking and triglycerides increased. These different trends might explain an increasing CHD incidence among younger women but decreasing incidence and mortality among older women.

Age Factors↗
PubMed1988

Differential outgrowth of retinal neurites on purified extracellular matrix molecules.

Organotypic cultures of the embryonic retina were used to study the influence of extracellular matrix molecules on neurite elongation during development of the central nervous system. Microexplants from the chick retina (embryonic day 6) were grown in medium containing appropriate trophic support on purified matrix molecules adsorbed to plastic at various concentrations. The maximum neurite length obtained on each type of substratum was measured on day 4 of culture. No fiber outgrowth occurred on substrata of vitronectin or a hyaluronate-binding chondroitin sulfate proteoglycan. In contrast, neurite elongation was strongly promoted on laminin in a dose-dependent manner. Fibronectin elicited a neurite outgrowth corresponding to about one-third the length of the outgrowth on laminin. A 31,000-dalton fibronectin fragment representing the heparin-binding domain elicited neurite elongation comparable to that promoted by the intact fibronectin molecule. Other isolated domains of fibronectin, including the 105,000-dalton "cell-binding" domain, did not allow neurite outgrowth. Furthermore, preincubation of fibronectin substratum with antibodies to the heparin-binding fibronectin fragment entirely prevented outgrowth. Fiber outgrowth was also evoked on substrata of platelet factor 4, a protein binding heparan sulfate. Adding increasing concentrations of heparin progressively inhibited the neurite extension on laminin, whereas similar addition of soluble chondroitin sulfate proteoglycan had no effect. The results indicate that growing retinal neurites show strong preference for laminin versus fibronectin. Moreover, the outgrowth-promoting activity of both cell adhesion proteins seems to be localized to their heparin-binding regions. It is suggested that during development of the visual system, elongating retinal neurites can actively discriminate between different extracellular molecules by a mechanism that may involve participation of cell surface heparan sulfate proteoglycans.

Animals↗
PubMed1988

Fibronectin fibril formation involves cell interactions with two fibronectin domains.

Fibronectin fragments and domain-specific antibodies have been used to study the mechanism by which cells reorganize exogenous fibronectin substrata into fibrils. Fibroblasts prevented from protein synthesis, and hence not secreting endogenous fibronectin or other matrix components, reorganized exogenous fibronectin substrata into arrays resembling the matrix of normally cultured cells. Cells also formed fibrils from substrata containing mixtures of cell- and either of two different heparin-binding fibronectin fragments but not from either fragment alone. The gelatin-binding fragment alone or in conjunction with the cell-binding fragment did not promote fibril formation. Antibodies recognizing cell- and either heparin- or the gelatin-binding domains labeled fibrils formed by cells under normal culture conditions or when a substratum of intact fibronectin was used as the sole exogenous source. However, only antibodies recognizing the cell- or either heparin-binding fragment reduced fibrillogenesis from intact fibronectin substrates when added during cell spreading. These data suggest that formation of fibronectin fibrils can occur at the cell surface and that membrane components recognizing the cell- and the heparin-binding domains in fibronectin may cooperate in the assembly process.

Animals↗