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Biomedical subjects

U Lindberg

Publications and source records attributed to U Lindberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Specificity of the interaction between phosphatidylinositol 4,5-bisphosphate and the profilin:actin complex.

Profilactin, the profilin:actin complex, which is present in large amounts in extracts of many types of eukaryotic cells, appears to serve as the precursor of microfilaments. It was reported recently that profilactin interacts specifically with phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (Lassing and Lindberg: Nature 314:472-474, 1985.) The present paper describes in detail the behaviour of profilactin and profilin in the presence of different types of phospholipids and neutral lipids under different conditions. PtdIns(4,5)P2 is the only phospholipid found so far which in the presence of 80 mM KCl and at Ca2+ concentrations below 10(-5) M effectively dissociates profilactin with the resulting polymerization of the actin. Phosphatidylinositol 4-monophosphate exhibits some activity but phosphatidylinositol is inactive. Both calf spleen profilin and profilin from human platelets form stable complexes with PtdIns(4,5)P2 micelles. PtdIns(4,5)P2 is active also when incorporated together with other phospholipids in mixed vesicles.

Actin Cytoskeleton↗
PubMed1988

Evidence that the phosphatidylinositol cycle is linked to cell motility.

Transmembrane signaling via specific ligand/receptor interactions induces the immediate polymerization of actin and formation of microfilament assemblies close to the plasma membrane. The profilin:actin complex appears to provide the actin for this filament formation. A clue to the nature of the regulatory mechanism involved was recently found in that phosphatidylinositol 4,5-bisphosphate can bind to profilin, dissociate the profilactin complex, and thus liberate actin for polymerization. This suggests that the phosphatidylinositol (PI) cycle, which plays important roles in cellular regulation, also might control microfilament-based motility. We show here that neomycin, a drug which has a high affinity for phosphoinositides and in vivo interferes with the PI cycle, inhibits the polymerization of actin in platelets induced either by thrombin or by ADP. When ADP was used as agonist (but not in the case of thrombin) the induction of actin polymerization could also be blocked by the addition of aspirin. Introduction of Ca2+ into platelets by the use of the ionophore A23187 or stimulation of protein kinase C (PkC) by the phorbol ester TPA did not induce actin polymerization; neither did the addition of a combination of these two agents. Retinoic acid which inhibits PkC was also without effect on thrombin-induced actin polymerization.

Actins↗
PubMed1987

Personality traits in subtypes of alcoholics.

Earlier studies have identified at least two distinct subgroups of alcoholics: Type II with early onset and high genetic loading and Type I with late onset in which genetic factors seem to be of minor importance. In the present study, type I and type II alcoholics are compared on stable personality traits determined by the Karolinska Scales of Personality. Both groups were found to have high scores on scales that measured somatic anxiety, psychic anxiety, muscular tension, impulsiveness, detachment, psychastenia, suspicion, guilt and inhibition of aggression. Both groups had low scores on the scale that measured socialization. Type II alcoholics had significantly higher scores than type I alcoholics on Somatic Anxiety and Verbal Aggression scales and significantly lower scores on Socialization and Inhibition of Aggression scales. On the Impulsive Sensation-Seeking Psychopathy factor (Impulsiveness + Monotony Avoidance - Socialization), type II alcoholics were significantly differentiated from both type I alcoholics and healthy volunteers. Results of this study were consistent with those of other studies indicating that alcoholism accompanied by antisocial behavior should be kept separate from alcoholism that is unrelated to antisocial behavior.

Adult↗
PubMed1986

The correlation between arthroscopic findings and the patellofemoral pain syndrome.

For this study, 1,784 arthroscopies were analysed. Abnormalities of the patellofemoral joint consisting of patellar malalignment and/or patellar chondral damage were present in 175 (10%). Two types of lesion were identified, distinguished by the alignment of the patellofemoral joint, namely, subluxation with or without chondral damage (group I) and chondral damage without subluxation (group II). Group I (mean age, 25 years) included a greater proportion of women than group II; in 72%, the predominant clinical feature was patellofemoral pain syndrome (PFPS). Group II (mean age, 43 years) included fewer women; PFPS was found in only 32%, but in 82% there were signs of degenerative joint disease, which could explain the symptoms. Patellar subluxation was correlated to the PFPS, whereas chondral damage alone was not.

Adult↗
PubMed1985

Time-resolved X-ray scattering study of actin polymerization from profilactin.

The polymerization of actin in solutions of purified calf spleen actin or profilactin (1-10 mg . ml-1) was followed by synchrotron radiation X-ray solution scattering. At the concentration used, polymerization of actin from profilactin or actin occurs without any lag phase. It is shown by a combination of solution scattering, model calculations and electron microscopy that contrary to the conclusions from previous viscometry studies, filaments form without any lag phase in profilactin solution but aggregate in bundles or networks. This phenomenon is independent of the method used to induce polymerization: slow temperature increase, temperature jump in the presence of polymerizing salts or fast mixing with salt. This aggregation explains the lower final viscosity levels, as compared to actin solutions, observed during the polymerization of actin from profilactin.

Actins↗
PubMed1985

Changes in the organization of actin and myosin in non-muscle cells induced by N-ethylmaleimide.

There is evidence from in vitro studies that the SH reagent N-ethylmaleimide (NEM) causes the formation of ATP-resistant rigor-complexes between actin and myosin, and NEM-modified heavy meromyosin has been used by Cande et al. to study the contractile process during cytokinesis. It is reported here that treatment of tissue-cultured cells with NEM causes an immediate cessation of all motile activities and a simultaneous stabilization of the ultrastructure of the cell visualized on lysis with detergent-containing buffers. After NEM treatment a 5- to 10-fold increase in the amount of myosin was found associated with the detergent-resistant cell residues. As suggested by immunoelectron microscopy, using antibodies to non-muscle myosin together with gold-labelled protein A, increasing amounts of myosin filaments became associated with the microfilament assemblies of the cell with time of NEM treatment. In addition to this there was a slow, progressive reorganization of the cortical wave of microfilaments. The structures interpreted as myosin filaments were visualized at relatively high resolution. The immunoelectron microscopy finally also indicated the presence of a non-filamentous form of myosin in agreement with the results of others.

Actins↗
PubMed1985

Urinary tract infection in children with type I diabetes.

The prevalence and incidence of bacteriuria in 304 girls and 337 boys with type I diabetes was studied by screening for bacteriuria at their regular outpatient controls. In 90 girls and 108 boys a urine specimen was sampled every third month during a year. The prevalence of bacteriuria was 3/304 in girls and 0/337 in boys. During the one year follow-up one of the 90 girls had pyelonephritis and two cystitis while none of the boys had bacteriuria. It is concluded that the rate of urinary tract infection in young diabetic persons does not differ from that present in healthy young people.

Adolescent↗
PubMed1984

Separation of non-muscle isoactins in the free form or as profilactin complexes.

Profilactin prepared from calf spleen by the standard procedure (Carlsson, L., Nyström, L.-E., Sundkvist, I., Markey, F., and Lindberg, U. (1977) J. Mol. Biol. 115, 465-483) can be further fractionated by chromatography on hydroxyapatite into two major peaks; one containing profilin in combination with gamma-actin (PA gamma) and the other combined with beta-actin (PA beta). Both complexes were shown to consist of 1 mol each of the two proteins. The two forms of profilin, PI (intact form) and PII (lacking the COOH-terminal glutamine and tyrosine residues) (Malm, B., Larsson, H., and Lindberg, U. (1983) J. Muscle Res. Cell Motil. 4, 569-588), were found unequally distributed between the two major peaks of PA, such that PA gamma contained mainly PI and PA beta both PI and PII. The significance of this finding remains unclear. Isoelectrofocusing showed that PI from both isoforms of PA had an isoelectric point of 9.08. Profilin II gave rise to two major bands on isoelectrofocusing having isoelectric points of 9.12 and 9.18, respectively. Finally it was shown that the two isoforms of actin can be separated from each other in the absence of profilin also by chromatography on hydroxyapatite. In this case, ATP remains bound to the actins eluted from the chromatographic matrix and both actins were shown to polymerize on addition of salts as judged by viscometry.

Actins↗
PubMed1984

The organization of microfilaments in spreading platelets: a comparison with fibroblasts and glial cells.

Platelets respond to stimulatory agents in general by the formation of long spikelike surface projections built up of tightly bundled microfilaments. During contact stimulation this is followed by a second phase when thin membrane lamellae grow out between the projections. This behaviour resembles that seen for instance in fibroblasts and glial cells, sending out microspikes and lamellipodia as a step in their advancement over solid substrata. Conditions, designed earlier for the preservation and visualization of the fragile organization of microfilaments and microtubules in the peripheral, highly motile parts (leading lamellae) of such cells (Höglund et al. (1980) J. Musc. Res. Cell Motility, 1:127-146), were used here to produce high-resolution images of the ultrastructural organization of platelets spreading on a solid substratum. This revealed an unexpected arrangement of actin filaments running parallel to the advancing edge, and small tufts of microfilaments on the outside of this edge-bundle. Cytochalasin D caused a regression of the spikelike projections as well as of both types of structures in the advancing platelet lamella and led to the appearance of a dense filamentous mat in juxtaposition to the plasma membrane. Analysis of the actin pools using the DNAase inhibition assay showed that the dramatic reorganizations of actin seen during the two phases of contact stimulation was reflected in a shift in the G/F-actin ratio only during the early phase.

Actins↗
PubMed1983

The profilin--actin complex: further characterization of profilin and studies on the stability of the complex.

Two forms of profilin can be isolated from calf spleen profilactin by chromatography on phosphocellulose. They can be distinguished by C-terminal analysis, which suggests that one of them lacks the C-terminal tyrosine and the penultimate glutamine residue. This is confirmed by treatment of profilin (+Tyr) with carboxypeptidase A, which removes the C-terminal tyrosine (rapidly) and the penultimate glutamine residue (slowly), and thereby converts it to the other form as judged by chromatography on phosphocellulose. The two forms of profilin differ also in solubility and in mobility during so-called 'charge shift' electrophoresis, indicating differences in their ability to bind detergents. Recombination studies using profilin with or without a modified C-terminus demonstrated that this part of profilin is relatively unimportant for the interaction with actin. On the other hand, experiments with native and modified actin revealed that the C-terminus of actin is of the utmost importance for the stability of the profilactin complex. Analysis of the u.v. absorbance and far-u.v. circular dichroism spectra of profilin and actin did not reveal any major changes in the conformation of the proteins accompanying the modifications at the C-terminal ends. Finally, it is reported that purified profilactin contains variable amounts of a protein factor which causes an apparent stabilization of profilactin in solution.

Actins↗
PubMed1983

The effect of platelet-derived growth factor on morphology and motility of human glial cells.

Platelet-derived growth factor (PDGF) is a mitogen for several cell types in culture. It is documented in this work that one of the earliest effects of PDGF on serum-starved glial cells is an induction of intensive motile activity. Within the first minute after the addition of PDGF thin membrane lamellae grow out around almost all of the cell circumference. Later, circular arrangements of small ruffles appear on the dorsal surface of the cells. These rings of ruffles vary in size and some encircle almost the whole cell. The organization of the peripheral weave of microfilaments in the PDGF-induced advancing lamellae was closely similar to that of normally growing cells. In the regions of the circular arrangements of ruffles there was an extensive reorganization of the surface actin with unusual arrangements of microfilament bundles and polygonal networks. There was also a general intensification of the translocation of membrane ruffles and spikes from the cell periphery towards the centre of the cell, increased micropinocytotic activity and shuttling of intracellular particles.

Cell Movement↗
PubMed1982

A 90 000-dalton actin-binding protein from platelets. Comparison with villin and plasma brevin.

Affinity chromatography of Ca2+-containing extracts of platelets on DNAase I-Sepharose, using Ca2+-free buffer as eluant, selects a 1:1 complex of a 90 000-dalton protein with actin. The complex shows little interaction with either DNAase or actin unless Ca2+ is present. In the presence of Ca2+, the complex nucleates polymerization of actin, reduces the viscosity attained, and delays filament formation from profilactin with characteristics closely resembling those shown by chicken villin. Proteolysis of the native proteins indicates structural similarity between the platelet protein and villin or villin core; limited proteolytic digestion in the presence of SDS distinguishes the platelet protein from villin but not from the functionally related plasma protein, brevin. The platelet protein is not accessible to enzyme-mediated iodination of surface components on intact cells. The term 'platelet brevin' is proposed for the protein.

Actins↗
PubMed1982

Nucleation of actin polymerization from profilactin. Opposite effects of different nuclei.

The lag in polymerization of calf spleen profilactin in response to addition of MgCl2 can be overcome by small amounts of spectrin-actin-band 4.1 complex, covalently crosslinked actin oligomers or sonicated F-actin. All of these factors also nucleate polymerization of pure actin. Another nucleator of actin polymerization, villin, delays filaments formation from profilactin. A simple model of the interaction of profilin with actin can explain these apparently conflicting results in terms of the polarity with which actin filaments elongate from the different nuclei.

Actins↗