Biomedical subjects

M Bergman

Publications and source records attributed to M Bergman.

At least 19 recordsLinked to original sources

PubMed1995

Effects of amiodarone on beating rate and Na-K-ATPase activity in cultured neonatal rat heart myocytes.

1. The purpose of this study was to examine the possibility that the cellular action of amiodarone is mediated by inhibition of thyroid hormone regulatory functions within the myocardial cell. We measured the rate of cell beating and the activity of Na-K-ATPase in cultured neonatal rat heart myocytes. 2. Amiodarone (0.25 and 1 microgram/ml) reduced beating rate up to 75% within 20 min, and Na-K-ATPase activity up to 40% within 2 hr. No toxic effects were detected in the treated cells. 3. The inhibitory actions of amiodarone on beating rate and Na-K-ATPase activity were the same in myocytes grown in the presence or absence of 3-iodothyronine (T3, 5 nM). 4. These data indicate that amiodarone affects beating rate and Na-K-ATPase activity independently of thyroid hormone. It is suggested that interference of amiodarone with thyroid hormone action is not the only mechanism by which this drug modulates some functions of the myocardial cell.

Amiodarone↗

PubMed1995

The use of combination internal fixation and hybrid external fixation in severe proximal tibia fractures.

Forty-eight patients with 50 severe fractures of the proximal tibia were followed prospectively for 2-4 years (mean 2.7 years) to evaluate the use of limited internal fixation combined with external fixation in the treatment of these injuries. There were 27 men and 21 women ranging in age from 20 to 74 years. Fractures were classified according to the A0 system (Mast J, Ganz R, Jacob R: Planning and reduction technique in fracture surgery. Berlin, Springer-Verlag, 1989), which included 5 A3, 6 C1, 16 C2, and 23 C3 fractures. All patients in this series healed; 48 fractures healed in an average of 12 weeks without subsequent surgery. There were two (4%) nonunions requiring bone graft. The average hospital special surgery knee score was 90 (68-100). Grading criteria for anatomical outcome revealed there were 17 (34%) excellent results, 24 (48%) good results, 6 (12%) fair results, and 3 (6%) poor results. In conclusion, this treatment method is associated with a high percentage of good and excellent results. Combined internal and external fixation combines the advantages of anatomic, stable fixation with less soft-tissue dissection and eliminates the need for large implants.

Adult↗

PubMed1995

Overexpressed Csk tyrosine kinase is localized in focal adhesions, causes reorganization of alpha v beta 5 integrin, and interferes with HeLa cell spreading.

The C-terminal Src kinase p50csk phosphorylates Src family tyrosine kinases and down-regulates their activity in vitro. To gain insight into the cellular functions of this potentially antioncogenic enzyme, we have overexpressed the csk cDNA by using an inducible promoter in HeLa cells. Despite some differences in basal Src activity in the clones analyzed, Src activity was not significantly suppressed, while the amount of p50csk and Csk activity increased at least 10-fold during 3 days of induction. Immunofluorescence for the induced p50csk was localized in the cytoplasm and distinctly in focal adhesions, in which the amount of phosphotyrosine containing proteins was also increased. Point and deletion mutagenesis experiments showed that localization in focal adhesions was dependent on the SH2 and SH3 domains of Csk but not on its catalytic activity. Csk formed a complex with the focal adhesion protein paxillin in cells, and its SH2 domain was shown to interact with pp125FAK and paxillin in vitro. After Csk induction, the cells became spherical and more loosely attached to the culture substratum, and the alpha v beta 5 integrin complex (vitronectin receptor) of focal adhesions was redistributed to a novel type of structure consisting of punctate plaques on the ventral cell surface. These phenotypic changes occurred in several clones analyzed and were totally reversible when Csk was switched off, but they did not occur in cells overexpressing the catalytically inactive Csk R-222 mutant or luciferase. Our results thus show that a fraction of cellular Csk is targeted to focal adhesions via its SH2 and SH3 domains, probably interacting with tyrosyl-phosphorylated focal adhesion proteins. They also suggest that Csk is involved in the regulation of integrins controlling cell attachment and shape.

CSK Tyrosine-Protein Kinase↗

PubMed1994

Rapid and efficient purification of Src homology 2 domain-containing proteins: Fyn, Csk and phosphatidylinositol 3-kinase p85.

To analyse the regulation of Src family tyrosine kinases in vitro, we have purified Fyn and Csk, a kinase capable of regulating Fyn activity by phosphorylation, from baculovirus-infected insect cells. The proteins were purified by affinity purification over a phosphotyrosine column. Highly purified proteins were eluted from the resin by a salt gradient and further purified by ion-exchange chromatography. This purification scheme was successfully applied to a third, unrelated protein that also contains the Src homology 2 (SH2) domain, namely the 85 kDa subunit of phosphatidylinositol 3-kinase, indicating that this method is versatile and should prove applicable to any protein with an accessible SH2 domain. The binding of Csk to different phosphopeptides was tested, and specificity for the autophosphorylation site of Fyn was demonstrated. Pure Csk was used to phosphorylate Fyn and down-regulate its kinase activity, and the kinetic parameters of both the active and the repressed forms of Fyn were determined. Repression of Fyn activity by Csk reduced binding of Fyn to phosphopeptides to undetectable levels, supporting the model that predicts an intramolecular interaction of the Fyn SH2 domain with a C-terminal phosphotyrosine residue.

Amino Acid Sequence↗

PubMed1994

Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1.

We have studied the signal transduction pathways of fibroblast growth factor receptor-4 (FGFR-4) and FGFR-1, which showed virtually identical acidic fibroblast growth factor binding profiles as well as tyrosine autophosphorylation upon activation in transfected L6 rat myoblasts and NIH3T3 mouse fibroblasts. A prominently tyrosyl-phosphorylated doublet of polypeptides of 85 kDa coprecipitated with activated FGFR-4 from both cell lines studied, but these polypeptides were not detected upon immunoprecipitation of activated FGFR-1. Furthermore, FGFR-4 induced only a weak tyrosyl phosphorylation of phospholipase C-gamma and no detectable tyrosyl phosphorylation of the SHC adaptor proteins in contrast to FGFR-1. No phosphorylation of Ras GTPase-activating protein, p64 Syp/PTP1D tyrosine phosphatase, or association of the GRB2 adaptor protein SH2 domain with these receptors was detected. Unlike FGFR-1, FGFR-4 induced only a barely detectable phosphorylation of the cellular serine/threonine kinase Raf-1 and a weaker tyrosyl phosphorylation of mitogen-activated protein kinases than FGFR-1. Despite these differences, stimulation of both receptors resulted in increased DNA synthesis.

3T3 Cells↗

PubMed1994

Tyrosine phosphorylation of CD45 phosphotyrosine phosphatase by p50csk kinase creates a binding site for p56lck tyrosine kinase and activates the phosphatase.

Src family protein tyrosine kinases (PTKs) play an essential role in antigen receptor-initiated lymphocyte activation. Their activity is largely regulated by a negative regulatory tyrosine which is a substrate for the activating action of the CD45 phosphotyrosine phosphatase (PTPase) or, conversely, the suppressing action of the cytosolic p50csk PTK. Here we report that CD45 was phosphorylated by p50csk on two tyrosine residues, one of them identified as Tyr-1193. This residue was not phosphorylated by T-cell PTKs p56lck and p59fyn. Tyr-1193 was phosphorylated in intact T cells, and phosphorylation increased upon treatment with PTPase inhibitors, indicating that this tyrosine is a target for a constitutively active PTK. Cotransfection of CD45 and csk into COS-1 cells caused tyrosine phosphorylation of CD45 in the intact cells. Tyrosine-phosphorylated CD45 bound p56lck through the SH2 domain of the kinase. Finally, p50csk-mediated phosphorylation of CD45 caused a severalfold increase in its PTPase activity. Our results show that direct tyrosine phosphorylation of CD45 can affect its activity and association with Src family PTKs and that this phosphorylation could be mediated by p50csk. If this is also true in the intact cells, it adds a new dimension to the physiological function of p50csk in T lymphocytes.

Amino Acid Sequence↗

PubMed1994

Rak, a novel nuclear tyrosine kinase expressed in epithelial cells.

We have identified a new tyrosine kinase from human breast cancer cells called Rak (a Russian word for cancer) that shares 51% identity with c-Src. Sequencing of the full-length complementary DNA revealed that Rak is a tyrosine kinase with a molecular weight of 54,000 that contains SH2 and SH3 domains, as well as tyrosine residues analogous to the autophosphorylation and regulatory tyrosines of the Src family. Biochemical and site-directed mutagenesis analyses revealed that a carboxy-terminal peptide of p54rak was phosphorylated by a cytoplasmic tyrosine kinase (CSK) and that, as in the Src family, it is the COOH-terminal tyrosine that is phosphorylated by CSK. However, there were some properties of Rak that are distinct from Src-like kinases: (a) expression of Rak was predominantly in epithelial-derived cell lines and tissues, especially normal liver and kidney, and cell lines of breast and colon origin; (b) Rak does not harbor the NH2-terminal glycine essential for myristylation and membrane localization; and (c) Rak possesses a putative bipartite nuclear localization signal in the SH2 domain, and subcellular fractionation studies revealed that p54rak resides predominantly in the nucleus. In addition, p54rak was overexpressed in subsets of primary human epithelial tumors, suggesting that p54rak may have a role in human cancer. Thus, Rak is a novel epithelial-associated nuclear tyrosine kinase that may represent a unique subfamily of the Src-related kinases.

Amino Acid Sequence↗

PubMed1993

Suppression of c-Src activity by C-terminal Src kinase involves the c-Src SH2 and SH3 domains: analysis with Saccharomyces cerevisiae.

The kinase activity of c-Src is normally repressed in vertebrate cells by extensive phosphorylation of Y-527. C-terminal Src kinase (CSK) is a candidate for the enzyme that catalyzes this phosphorylation. We have used budding yeast to study the regulation of c-Src activity by CSK in intact cells. Expression of c-Src in Saccharomyces cerevisiae, which lacks endogenous c-Src and Y-527 kinases, induces a kinase-dependent growth inhibition. Coexpression of CSK in these cells results in phosphorylation of c-Src on Y-527 and suppression of the c-Src phenotype. CSK does not fully suppress the activity of c-Src mutants lacking portions of the SH2 or SH3 domains, even though these mutant proteins are phosphorylated on Y-527 by CSK both in vivo and in vitro. These results suggest that both the SH2 and SH3 domains of c-Src are required for the suppression of c-Src activity by Y-527 phosphorylation.

CSK Tyrosine-Protein Kinase↗

PubMed1992

The human p50csk tyrosine kinase phosphorylates p56lck at Tyr-505 and down regulates its catalytic activity.

Protein tyrosine kinases participate in the transduction and modulation of signals that regulate proliferation and differentiation of cells. Excessive or deregulated protein tyrosine kinase activity can cause malignant transformation. The catalytic activity of the T cell protein tyrosine kinase p56lck is normally suppressed by phosphorylation of a carboxyl-terminal tyrosine, Tyr-505, by another cellular protein tyrosine kinase. Here we characterize a human cytosolic 50 kDa protein tyrosine kinase, p50csk, which specifically phosphorylates Tyr-505 of p56lck and a synthetic peptide containing this site. Phosphorylation of Tyr-505 suppressed the catalytic activity of p56lck. We suggest that p50csk negatively regulates p56lck, and perhaps other cellular src family kinases.

Amino Acid Sequence↗

PubMed1992

The c-src tyrosine kinase (CSK) gene, a potential antioncogene, localizes to human chromosome region 15q23----q25.

We have previously reported the cloning of a novel cytoplasmic tyrosine kinase, CSK. This tyrosine kinase has been shown to downregulate the tyrosine kinase activity of the c-src oncoprotein through tyrosine phosphorylation of the c-src carboxyl terminus. Cell transformation by src oncoproteins is caused by several oncogenic mechanisms, which interfere with this phosphorylation. The CSK gene could therefore potentially function as an antioncogene. We have here mapped the CSK gene to 15q23----q25 by in situ hybridization.

CSK Tyrosine-Protein Kinase↗

PubMed1992

Daily dose calculations from measurements of intra-oral mercury vapor.

Measurements of intra-oral mercury vapor from amalgam fillings are discussed. It was shown that the only quantity which it is possible to measure is the mercury release rate, and that the concentrations of mercury vapor in the oral cavity published in most earlier studies are the mercury concentrations in the measuring cell of the measuring apparatus and not the concentrations in the oral cavity. The consequences for the daily dose equations of the facts that the mercury source is present inside the oral cavity and that the amount of mercury released during a certain time is limited are discussed. It was found that most daily dose equations used have a questionable mercury distribution on inspiration, expiration, and swallowing. Re-calculations of almost all the available daily dose data showed a mean daily dose value of about 1.3 micrograms Hg/day (range, 0.3-2.2 micrograms Hg/day). The mean swallowed amount of mercury from intra-oral mercury vapor was calculated as being in the order of 10 micrograms Hg/day (range, 2.4-17 micrograms Hg/day), resulting in an estimated absorption of about 1 microgram Hg/day from the gastro-intestinal tract.

Air Pollution, Indoor↗

PubMed1992

A clinical examination of ceramic (Cerec) inlays.

Two hundred and five Cerec ceramic inlays placed by 8 dentists in 72 patients were examined independently by 3 calibrated evaluators 12-24 months after insertion, using the criteria of the California Dental Association (CDA) and also certain periodontal variables. Proximal dental plaque and bleeding on probing were not seen more often on Cerec surfaces than on control homologous surfaces. Ten patients reported postoperative sensitivity after treatment with Cerec inlays. Excellent CDA ratings for Color and Surface were obtained in 57% and 26%, respectively, and for Anatomic Form and Margin Integrity in 55% and 83%, respectively. Obvious differences were seen among the participating dentists with regard to the clinical quality of Cerec inlays. At present, the long-term performance of the Cerec technique cannot be predicted.

Adolescent↗

PubMed1992

Piezoelectricity in dental materials, a conceivable cause of postrestorative sensitivity.

With the increased use of tooth-colored posterior inlays reports of postrestorative sensitivity have also increased. One of the symptoms the patients complain of is a sharp pain when the inlays are loaded through chewing and biting. Many explanations for the causes of dissimilar types of postrestorative sensitivity have been offered, but one conceivable explanation that has not hitherto been studied is the direct piezoelectric effect in dental materials. Direct piezoelectric effect means that when certain anisotropic crystals are mechanically loaded, a charge is generated on the surface. The aim of the present study was to examine whether this physical phenomenon occurs in certain materials intended for dental use. Specimens of four different dental ceramics and one indirect composite resin for inlays were mechanically loaded with various forces, and the current was directly recorded. Currents of up to 0.9 microA with a pulse duraton of 0.4 msec were extracted, and it cannot be excluded that the piezoelectric phenomenon and related properties may cause postrestorative sensitivity. This has to be taken into consideration when posterior inlays of the types concerned are used.

Acrylic Resins↗

PubMed1992

Frequency selectivity as a potential measure of noise damage susceptibility.

The notched-noise procedure of Patterson (1974, Journal of the Accoustical Society of America, 55, 802-809; 1976, Journal of the Acoustical Society of America, 59, 640-654) was employed in revealing changes in auditory frequency selectivity (FS) in noise-exposed industrial workers in manufacturing plants in which noise levels in the working environment exceeded 90 dB(A). With 4 kHz as the test frequency, both threshold and FS measures were applied to three groups of non-exposed young adults (total N = 61) for reference values and to workers in three different factories, some ('noise-exposed') working in noise levels over 90 dB(A) (total N = 222). In another study involving 185 workers only the FS test was repeated after a work session, and the results are reported on 31 who worked in high noise levels. Pre-work-shift data showed that when thresholds were better than 30-dB HL most FS values were 10 dB or more, while subjects with hearing threshold levels beyond that showed reduced FS. Two post-work-shift studies of 144 ears of the noise-exposed workers showed significant deleterious changes in both thresholds and FS but the relationships were different in the two studies. The findings indicate that the notched-noise test is sensitive to noise-induced auditory damage, even after a single work-shift. Attractive features of the procedure are that it reduces the need for a quiet test environment and that it can be more resistant to testee manipulation or threshold 'learning' effects, often seen in industrial audiometric testing.

Acoustics↗

PubMed1992

The castability of unalloyed titanium in three different casting machines.

The general demand for a variety of fine detail work made of titanium has resulted in the development of equipment/systems for the casting of this metal. Dental casting machines suitable for the casting of titanium are now also available. The aim of the present study was therefore to evaluate the possibility of precision casting of dental crown restorations of unalloyed titanium. The three kinds of casting equipment currently used in Sweden were tested by evaluating the crown edge diameter of 10 titanium crowns processed by each one of the titanium casting machines. The results revealed that clinically acceptable margins can be obtained but also that further improvements in processing have to be achieved before titanium casting can be considered as uncomplicated as the casting of traditional dental gold alloys.

Crowns↗

PubMed1992

Base plate wax, dimensional stability and sorption of active components following treatment with disinfectant solutions.

The influence of seven disinfectants on the dimensional stability of a base plate wax, Tenax, was studied. Two methods for treatment were tested - immersion for one hour and spraying respectively. After spraying no significant influence on the wax could be established and after immersion four of the seven disinfectants, including Cidex and K-644, likewise had no significant influence on the dimensional stability. The wax specimens did not show any significant weight increase (less than one per cent) after immersion for four days but in four disinfectant solutions the surface properties of the wax specimens had changed showing that active components of the disinfectants were absorbed into or adsorbed on the wax surface.

Absorption↗

PubMed1992

Intraocular pressure level in glaucomatous and nonglaucomatous eyes after complicated cataract surgery and implantation of an AC-IOL.

The effects of a semiflexible, one-piece, open-loop anterior-chamber intraocular lens (AC-IOL) implanted after intracapsular or extracapsular cataract extraction complicated by posterior-capsular or zonular rupture on intraocular pressure (IOP) level and the control of previous glaucoma were studied in 48 eyes with primary implantation and in 10 eyes with secondary implantation. Fifty-four percent of the eyes with primary implantation had exfoliation syndrome; anterior vitrectomy was performed in 60.4%. An immediate pressure rise (IOP greater than or equal to 30 mm Hg) was observed in 29.3% of the eyes. The long-term IOP level (median follow up, 21.5 months) was less than or equal to 20 mm Hg in 83.7% and between 21 and 29 mm Hg in the remaining 16.3%. In three of the nine glaucomatous eyes, the medication had to be increased; in the remaining six, the IOP could be controlled with the previous or reduced medication or with none at all. In three out of the 49 (6.1%) nonglaucomatous eyes, glaucoma medication was started during the follow up. All of these eyes had exfoliation syndrome and two of the fellow eyes had similar IOPs and were receiving similar medication. The results indicate that the semiflexible, open-loop AC-IOL has little effect on IOP and seems to be a safe alternative, even in glaucomatous eyes, if a posterior chamber lens cannot be used.

Adult↗

PubMed1991

The effect of dietary vitamin E and beta-carotene on oxidation processes in the rat testis.

The effects of dietary vitamin E and beta-carotene were studied on enzymes involved in arachidonic acid metabolism and other related enzymes in the rat testis. Groups of rats were fed various soybean oil-based semi purified diets. Group 1 was fed a vitamin E-supplemented diet (+E - beta); Group 2 was fed a beta-carotene-supplemented diet (-E + beta); Group 3, the control group (-E - beta) was fed a vitamin E-deficient diet; and Group 4, the standard diet group (S), was fed vitamin E plus beta-carotene-standard diet. Soybean oxidized oil was added to the three diet groups - (+E - beta), (- E + beta) and (- E - beta), whereas the diet of S group contained non-oxidized oil. After 8 weeks rats were killed, blood and testis samples were collected for biochemical determinations. Vitamin E deficiency caused significant increase in testis thiobarbituric acid value and activities of testis NADPH oxidase, testis 15-lipoxygenase and in plasma pyruvate kinase. In contrast, significant decreases were observed in activity of testis prostaglandin synthetase, compared with antioxidant-supplemented diet groups. We also found a significant increase in 15-lipoxygenase activity in (- E + beta) diet group, compared with (- E - beta) diet group. Fatty acid analysis of testis parenchyma indicated decrease in palmitate (16:0) and arachidonate (20:4(n - 6)), and increase in oleate (18:1(n-6)) linoleate (18:2(n - 6)) and linolenate (18:3(n - 3)), when compared (-E - beta) diet group with vitamin E-supplemented diet groups. The results suggest that dietary vitamin E has a role in both enzymatic and non-enzymatic peroxidation of polyunsaturated fatty acids in the testis.

Animals↗