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L Carlsson

Publications and source records attributed to L Carlsson.

At least 19 recordsLinked to original sources
PubMed1997

Targeted disruption of the V(H) 81X gene: influence on the B cell repertoire.

We have generated a mutant mouse in which the most D-proximal V(H) gene (V(H)81X) has been disrupted by introducing a neomycin-resistance gene into the V(H)81X exon by means of gene targeting in embryonic stem cells. The mutant mice generated are unable to express the V(H)81X gene but appear to display a normal pattern of B cell differentiation as well as normal numbers of bone marrow and peripheral B cells from fetal life all through ontogeny. They mount normal immune responses to several different antigens tested. In contrast, the distribution of V(H) gene rearrangements in the V(H)7183 family is altered in homozygous mutant mice. Thus, the antibody repertoire of the targeted mice is modified, at least as far as the expression of V(H)7183 genes is concerned.

Animals↗
PubMed1997

Myringotomized mice develop myringosclerosis in the pars flaccida and not in the pars tensa.

The development of myringosclerosis has been correlated with increased production of oxygen-derived free radicals. For the present study, we used a null mutant mouse lacking extracellular superoxide dismutase to test the hypothesis that increased production of free radicals can cause the development of myringosclerosis. Null mutant mice and wild-type, control mice were myringotomized and kept in ambient air for 3 weeks. Both groups developed myringosclerosis in the pars flaccida, but not in the pars tensa. The sclerotic lesions were visible in both the light and the electron microscope but not in the otomicroscope. In particular, the localization of the sclerotic deposits was found beneath both the inner and outer epidermal epithelium. No difference concerning the extent or number of sclerotic lesions between the null mutant and the wild-type mice could be distinguished.

Animals↗
PubMed1996

Accuracy of machine milling and spark erosion with a CAD/CAM system.

A method for manufacturing crowns and fixed partial dentures based on CAD/CAM has been developed as an alternative to the lost wax technique and the casting of an alloy. In this process two steps are included: milling and spark erosion. The computer-assisted design (CAD) relies heavily on the accuracy of the milling and spark erosion processes to achieve a clinically acceptable restoration. These two processes must be able to produce the crown data generated in the CAD files. This study evaluated the accuracy of the Procera CAD/CAM system in creating specific geometric bodies that were compared with the known dimensions in the CAD files for these bodies. The manufacturing errors of milling (ellipse +/- 6.5 microm, square +/- 3.4 microm, and cylinder +/- 5.8 microm) and spark erosion (ellipse +/- 8.6 microm and square +/- 10.4 microm) were determined. The accuracy of this manufacturing process demonstrated that this system was capable of producing a crown with a clinically accepted range for marginal opening gap dimension of less than 100 microm.

Analysis of Variance↗
PubMed1996

Measuring fit at the implant prosthodontic interface.

Four centers in the United States and Sweden have been working for 2 years to develop systems and methods for measuring fit at the prosthodontic interface. Two systems are based on stylus contact techniques, one system uses a laser as its reader source, and one system is photogrammetric. All the systems are capable of providing data as three-dimensional x, y, and z axes coordinate values that can be transformed into linear and angular data that characterize the bearing surfaces of abutments or abutment replicas and their mating components in the prosthesis framework. The centroid, a single point computed from the collected data, was the measurement unit, derived for these bearing surfaces, that was used to compare the systems. All four methods can most likely detect misfits that are relevant in the clinical setting; however, only one system can be used intraorally. When any measurement system is assessed, the data should always be examined for repeatability to establish the reliability of the system. This investigation made comparisons among the measurement methods used at the four centers. It was apparent from this study that comparisons of data from measurement systems should be rounded to the nearest 10 microns. The SDs determined in the comparisons were larger than 5 microns and therefore misfits should be calculated in terms smaller than 10 microns. This final point is important to the clinician who relies on research reports about precision of fit when selecting treatment approaches in caring for the implant prosthodontic needs of their patients.

Calibration↗
PubMed1996

Electrophysiological and inotropic characterization of a novel class III antiarrhythmic agent, GLG-V-13, in the mammalian heart.

GLG-V-13, a novel 3,7-diheterabicyclo(3.3.1)nonane, was examined both in vivo and in vitro to characterize its electrophysiological, hemodynamic, and inotropic properties. In anesthetized guinea pigs, GLG-V-13 [0.5-500 micrograms/kg intravenously (i.v.), n = 6] lengthened the epicardial monophasic action potential (MAP) duration, the atrioventricular (AV) conduction time and the RR interval in a dose-dependent manner. At the highest dose, these variables were increased by 30, 13, and 23%, respectively. No significant effects were noted on QRS duration or blood pressure (BP). In rabbit atrial and papillary muscle preparations, GLG-V-13 (0.32-3.2 mg/L) did not exert a negative inotropic action and in isolated rabbit cardiomyocytes the agent blocked the rapidly activating delayed rectifier K+ current (IKr, EC50 = 48 micrograms/L). In 10 intact anesthetized mongrel dogs, the left ventricular (LV) endocardial MAP was measured during atrial pacing before and after administration of GLG-V-13 (3 and 6 mg/kg i.v.). As compared with the drug-free state, the agent induced a significant prolongation of the MAP at all pacing frequencies (2.0-4.5 Hz). In 15 anesthetized dogs studied 1-4 days after two-stage ligation of the left anterior descending coronary artery (LAD), the antiarrhythmic/proarrhythmic potential of GLG-V-13 was compared with that of lidocaine. ECG, His bundle, LV (IZepi), and composite and normal zone composite electrograms were recorded. Programmed electrical stimulation (PES) and burst pacing (4.0-7.0 Hz) were delivered to the right ventricular outflow tract. In the drug-free state, sustained monomorphic ventricular tachycardia (SMVT) was inducible in 6 dogs (6 of 15). After lidocaine, SMVT was induced in 7 other dogs (13 of 15). GLG-V-13 prevented induction of SMVT in 5 of 6 dogs; a proarrhythmic action was noted in 1 dog only. GLG-V-13 slowed the heart rate (HR), increased the AH and the HV intervals, prolonged the paced (2.5 Hz) QT interval, and increased the ventricular effective refractory period (VERP). These effects were associated with 2:1 block of late potentials in the IZepi electrograms, a phenomenon also observed during rapid atrial pacing (2.5-3.5 Hz), suggestive of a marked prolongation of refractoriness in the ischemically damaged myocardium. In light of the recent Cardiac Arrhythmia Suppression Trial (CAST) study, the antiarrhythmic efficacy, together with the low proarrhythmic potential and lack of cardiodepressant properties of GLG-V-13, may merit further investigation of this novel class III antiarrhythmic agent.

Animals↗
PubMed1996

Lidocaine and nisoldipine attenuate almokalant-induced dispersion of repolarization and early afterdepolarizations in vitro.

INTRODUCTION: Treatment with Class III antiarrhythmic agents may lead to increased dispersion of repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na(+)- or Ca(2+)-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. METHODS AND RESULTS: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent almokalant (0.1 microM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33% +/- 4.2%, n = 18) than in the VM (17% +/- 5.9%, n = 18, P < 0.05). In six of the preparations, addition of 1, 5, and 25 microM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 microM lidocaine, the remaining prolongation was 7% +/- 12.2% (P < 0.05 vs time controls) in the PF and 14% +/- 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 microM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, but attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with almokalant (0.3 and 1 microM, respectively) at an APD of 828 +/- 41.4 msec. In six separate preparations pretreated with lidocaine (5 microM), the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 microM) did not influence the response to almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. CONCLUSION: At concentrations that did not affect the APD in the VM but reduced the APD in the PF, lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, on the other hand, inhibited almokalant-induced EADs directly. Hence, the primary APD-prolonging effect of a Class III agent may be preserved, but the risk of proarrhythmias reduced, during concomitant treatment with low concentrations of a Na(+)- or Ca(2+)-blocking agent.

Action Potentials↗
PubMed1996

Rhythm anomalies related to delayed repolarization in vivo: influence of sarcolemmal Ca++ entry and intracellular Ca++ overload.

The present study examined how Ca++ entry and intracellular Ca++ overload may contribute to the appearance of torsades de pointes in the setting of delayed repolarization. In anesthetized rabbits, the infusion of methoxamine and the selective I kappa s blocker almokalant (8.8 micrograms/kg.min) was associated with a lengthening of the QTU interval (37 +/- 2.6 ms, P < .001) and the appearance of torsades de pointes in 9/10 rabbits. In rabbits pretreated with nisoldipine (7.7 or 37 micrograms/kg i.v.), the incidence of almokalant-induced torsades de pointes was reduced to 7/10 (P = .5820 vs. vehicle) and 1/10 (P = .0006) rabbits, respectively. This occurred without attenuating the QTU-prolonging effect of almokalant (47 +/- 7.0 ms and 56 +/- 8.6 ms, respectively). Likewise, pretreatment with flunarizine (0.5 or 3.0 mg/kg i.v.) reduced the incidence to 1/6 (P = .0076) and 0/6 animals (P = .0009), respectively. In 10 of the rabbits that were given nisoldipine or flunarizine and did not experience torsades de pointes with almokalant, BAY K 8644 (0.11 mg/kg) was injected. In six of these rabbits, BAY K 8644 promptly induced torsades de pointes. In four vehicle-pretreated rabbits that experienced torsades de pointes with almokalant, acute injection of nisoldipine (37 micrograms/kg) abruptly suppressed the proarrhythmia. In separate experiments, rabbits were treated with ryanodine or BAPTA-AM and were subsequently administered almokalant. Compared with the vehicle-pretreated rabbits, these interventions did not significantly reduce the incidence of torsades de pointes (from 6/5 rabbits to 3/8 and 3/8 rabbits, respectively, P = .1776). The results demonstrate that Ca++ entry through the L-type Ca++ channel may be of crucial importance for the induction of torsades de pointes in the acquired long QT syndrome.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Expression of Fc gamma RIII defines distinct subpopulations of fetal liver B cell and myeloid precursors.

We have isolated four distinct fetal liver (FL) populations based on the expression of AA4.1 and the low-affinity Fc gamma receptors type II and III (Fc gamma RII/III), and characterized them with respect to B cell, T cell, and myeloid precursor content. Polymerase chain reaction analysis revealed that the prevalent Fc gamma R isoform at this stage of FL development (day 12 of gestation) was Fc gamma RIII. Two of the four populations, one which expressed AA4.1 but little if any Fc gamma RII/III (AA4.1+), and one which expressed abundant levels of both markers (AA4.1+/FcR+), contained B cell precursors that grew and differentiated to generate VHDJH-rearranged B-lineage cells on S-17 stromal cells in the presence of IL-7. When cultured on FLST2 stromal cells only the AA4.1+ cells generated VHDJH-rearranged B-lineage cells. T cell precursors as assayed by their ability to repopulate fetal thymi in organ culture were found only in the AA4.1+ fraction. In contrast to the lymphoid precursors, myeloid precursors able to generate colonies in methyl cellulose cultures were found in all four fractions including the one which expressed Fc gamma RII/III but no AA4.1 (FcR+) and the one which expressed neither marker (AA4.1-/FcR-). The AA4.1+ population which contained both B cell and T cell precursors was enriched for precursors from many myeloid lineages including the most immature ones which generated multilineage colonies. In contrast, the AA4.1+/FcR+ population, which also contained B cell precursors, was almost devoid of myeloid precursors and the few that were detected were committed to the macrophage lineage. The population defined as FcR+ was also enriched for precursors; however, the majority of these were committed to the erythroid, the macrophage and the mast cell lineage. The fourth population which expressed neither marker (AA4.1-/FcR-) was enriched for relatively mature erythroid precursors which were not present in any of the other fractions. Together, these findings demonstrate that fractionation of FL cells on the basis of AA4.1 and Fc gamma RII/III expression distinguishes subpopulations of B cell and myeloid precursors and suggests that the low-affinity Fc gamma RIII could play a role in the development of early hematopoietic cells at this stage of ontogeny.

Animals↗
PubMed1995

A specific and sensitive method for the determination of linamarin in Urine.

A method is described for the quantitative determination of the cyanogenic glycoside linamarin. A preseparation procedure for urine samples was necessary to remove interfering substances. This was done by solid-phase extraction on a silica column containing cyclohexyl functional groups, which retained linamarin but allowed thiocyanate to pass unrestricted through the column. After elution of linamarin from the column by 35% (v/v) aqueous methanol, the glycoside was quantified following enzymatic hydrolysis, using the specified enzyme linamarase, and the free cyanide thus liberated was estimated spectrophotometrically. This method allowed quantification of linamarin in urine down to 10 mumol/l, with an estimated recovery of 91%. In 75 Tanzanian subjects consuming insufficiently processed cassava, the mean (+/- SD) urinary linamarin concentration was 104 (+/- 104) mumol/l (range 0 - 644 mumol/L), while that for thiocyanate was 486 (+/- 451) mumol/l (range 10-2,940 mumol/l), giving an approximate 1:5 molar concentration ratio between urinary linamarin and thiocyanate.

Chromatography, Affinity↗
PubMed1995

Prevention of class III-induced proarrhythmias by flecainide in an animal model of the acquired long QT syndrome.

The influence of the class Ic agent, flecainide, on the incidence of class III-induced torsades de pointes was examined in an animal model of the acquired long QT syndrome. Twenty-four chloralose-anaesthetized rabbits were pretreated at random with flecainide or vehicle and subsequently given a concomitant infusion of methoxamine and the class III antiarrhythmic agent almokalant. In seven out of eight vehicle-treated rabbits, almokalant induced torsades de pointes which was preceded by a significant lengthening of the JTU interval (used as an indirect measure of ventricular repolarization time) by 55 +/- 9.2 msec. Flecainide dose-dependently reduced the incidence of almokalant-induced torsades de pointes. Hence, in a group of rabbits given a low dose (0.14 mumol/kg + 1.4 mumol/kg/hr) of flecainide, four out of eight animals experienced torsades de pointes (P = 0.1538 versus vehicle) whereas no case (n = 8) was observed after a higher dose (4.8 mumol/kg + 4.8 mumol/kg/hr, P = 0.0007). In the former group almokalant induced a maximal increase in the JTU interval not differing from that seen in the vehicle-treated group (58 + 12.1 msec, P > 0.05). Pretreatment with the high dose of flecainide, however, caused a significant attenuation of the almokalant-induced lengthening of the JTU interval (18 +/- 6.5 msec. P < 0.05). It is concluded that flecainide reduces the risk of proarrhythmia in the setting of delayed repolarization partially by attenuating the primary electrophysiological effect of class III agents.

Adrenergic alpha-Antagonists↗
PubMed1995

Electrophysiological characterization of a novel class III antiarrhythmic agent, GLG-V-13 in the mammalian heart.

GLG-V-13, a novel 3,7-diheterabicyclo[3.3.1]nonane, was examined both in vivo and in vitro in order to characterize its electrophysiological, haemodynamic and inotropic properties. Left ventricular epicardial monophasic action potential (MAP), surface ECG and mean arterial blood pressure (MBP) were recorded in six pentobarbital-anaesthetized, artificially ventilated and thoracotomized guinea-pigs. When studied in an intravenous dose interval ranging between 0.5 micrograms/kg and 500 micrograms/kg, GLG-V-13 dose-dependently lengthened the MAP duration (p < 0.05 at doses above 5 micrograms/kg), the atrioventricular conduction time (p < 0.05 at doses above 1 microgram/kg) and the RR interval (p < 0.05 at doses above 25 micrograms/kg). At the highest dose (500 micrograms/kg) these variables were increased by 30%, 13% and 23%, respectively. Only minor effects were noted on intraventricular conduction time (QRS interval) and MBP. In rabbit atrial and papillary muscle preparations, GLG-V-13 (0.32 to 3.2 mg/l) did not exert negative inotropic action. In 10 intact anaesthetized mongrel dogs, left ventricular endocardial MAP at 90% repolarization (MAP90) was measured during atrial pacing before and after administration of GLG-V-13, 3 and 6 mg/kg i.v., respectively.

Action Potentials↗
PubMed1995

Roentgen stereophotogrammetric analysis as a predictor of mechanical loosening of knee prostheses.

The tibial components in 143 patients with total knee replacements performed before 1988 were assessed for micromotion using roentgen stereophotogrammetric analysis (RSA) over a period of 13 years. The fixation of the prostheses remained clinically sound in all cases, although revision had been required for other reasons in seven. In a second group taken from all cases with RSA available on our full database to 1990, 15 tibial components had been followed by RSA from the insertion until, 1 to 11 years after the initial arthroplasty, they were revised for mechanical loosening of the tibial component; 12 of these comprised all the loosenings in the base group, thus making a total of 155 consecutive cases, while an additional three were inserted after the base material had been compiled. The mean migration in the first group was about 1 mm at one year, but subsequent migration was slower, reaching a mean of about 1.5 mm after ten years. About one-third migrated continuously throughout follow-up, while two-thirds ceased to migrate after one to two years. In the revision group, 14 components had migrated continuously and at one year significantly more than those in the first group. One revision case lacked the crucial one-year follow-up and could not be classified. These findings suggest that mechanical loosening begins early in the postoperative period. Clinical symptoms which necessitate revision, seen at this stage in 20% of abnormally migrating tibial components, may not appear until up to ten years after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Insulin-promoter-factor 1 is required for pancreas development in mice.

The mammalian pancreas is a mixed exocrine and endocrine gland that, in most species, arises from ventral and dorsal buds which subsequently merge to form the pancreas. In both mouse and rat the first histological sign of morphogenesis of the dorsal pancreas is a dorsal evagination of the duodenum at the level of the liver at around the 22-25-somite stage, and shortly thereafter a ventral evagination appears as a derivative of the liver diverticulum. Low levels of insulin gene transcripts are already present and restricted to the dorsal foregut endoderm at 20 somites, suggesting that pancreas- or insulin gene-specific transcriptional factors are present in this region before the onset of morphogenesis. Insulin-promoter-factor 1 (IPF1) is a homeodomain protein which, in the adult mouse pancreas, is selectively expressed in the beta-cells and binds to and transactivates the insulin promoter. In mouse embryos, IPF1 expression is restricted to the developing pancreatic anlagen and is initiated when the foregut endoderm is committed to a pancreatic fate. We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas. The mutant pups survive fetal development but die within a few days after birth. The gastrointestinal part and all other internal organs were normal in appearance. No pancreatic tissue and no ectopic expression of insulin or pancreatic amylase could be detected in mutant embryos and neonates. These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation.

Animals↗
PubMed1994

Bone response to hydroxyapatite-coated and commercially pure titanium implants in the human arthritic knee.

Rough and smooth commercially pure (c.p.) titanium implants and hydroxyapatite-coated (HA-C) implants were inserted in arthritic human knees and left in situ in order to compare the response of bone to these three implants. Radiographic examination alone could not determine if bone apposition had occurred. After 3 and 6 months, histomorphometric analyses of undecalcified sections, 10 microns thick, revealed a statistical significance in the amount of bone apposition to rough-surfaced and HA-C implants as compared with smooth uncoated implants. Most of the rough-surfaced c.p. titanium implants and the HA-C implants had achieved bone apposition on the order of 50%. No statistically significant differences in apposition were seen between the rough-surfaced and HA-C implants. The smooth c.p. titanium implants were mostly encapsulated in fibrous tissue.

Arthritis↗
PubMed1994

A gene family encoding heterogeneous histone H1 proteins in Trypanosoma cruzi.

A gene family encoding a set of histone H1 proteins in Trypanosoma cruzi is described. The sequence of 3 genomic and 4 cDNA clones revealed the presence of several motifs characteristic of histone H1, although heterogeneity at the polypeptide level was evident. The clones encode histone H1 proteins of an unusually small size (74-97 amino acids), which lack the globular domain found in histone H1 of higher eukaryotes. All histone H1 mRNAs from T. cruzi are polyadenylated, although no typical polyadenylation signal was found. Furthermore, the genes encoding the histone H1 proteins in T. cruzi are found in a tandem array containing 15-20 gene copies per haploid genome. This tandem array is located on a large chromosome of 2.2 Mb.

Amino Acid Sequence↗
PubMed1994

Induction of rhythm abnormalities in the fetal rat heart. A tentative mechanism for the embryotoxic effect of the class III antiarrhythmic agent almokalant.

OBJECTIVES: The aim was to test the hypothesis that the recently reported embryotoxic effect of class III antiarrhythmic agents may be a result of electrophysiological disturbances induced by these agents. METHODS: Comparative studies of drug effects in the adult and fetal rat were performed using three experimental models: (1) effects of almokalant upon pregnancy and fetal mortality in rats given daily doses of 0, 10, 50, 100, or 400 mumol.kg-1 orally in the diet on days 6-15 of pregnancy; (2) effects of d-sotalol (1-1000 microM), almokalant (0.1-100 microM) and dofetilide (0.01-10 microM) on the adult and fetal cardiac action potential in vitro; (3) voltage clamp recordings in single fetal and adult ventricular myocytes superfused with almokalant (0.5 microM). RESULTS: In the groups of rats treated with 100 and 400 mumol.kg-1, respectively, the body weight gain was decreased from day 12 of gestation, and there were no viable fetuses at termination of pregnancy. In atrial as well as ventricular tissue, the class III agents induced a concentration dependent prolongation of the fetal action potential duration, accompanied by a reduction in heart rate and eventually the appearance of rhythm abnormalities and/or early afterdepolarisations. The adult action potential duration remained unaffected. An almokalant sensitive current (probably the delayed rectifier, IK) could be evoked both in the fetal and in the adult ventricular cells. CONCLUSIONS: Class III antiarrhythmic agents were shown to induce fetal mortality and rhythm abnormalities in the rat heart. Although they do not prove a causal relationship between these effects, our observations may have implications for the clinical use of class III antiarrhythmic agents in women of childbearing potential.

Action Potentials↗
PubMed1994

Assay systems for the growth hormone-binding protein.

The first method used for detection of growth hormone-binding protein (GHBP) in biological fluids was based on the incubation of the sample with radiolabeled GH followed by separation of bound and free GH by gel exclusion chromatography. Recently, other methods have been developed which are faster and easier to use. These methods include variants of the original binding/column assay (e.g., separation of bound and free GH is obtained by immunoprecipitation, charcoal adsorption, ion exchange chromatography, or HPLC), and a ligand-mediated immunofunctional assay (LIFA), in which a monoclonal antibody is used to capture the GHBP on a microtiter plate; all binding sites are saturated with GH and an anti-GH antibody is used to detect the amount of GH (endogenous and exogenous) bound to the GHBP. To permit comparison of results obtained by different methods we have cross-validated the LIFA with two different binding assays: (i) the original long column assay (column assay), and (ii) an assay based on immunoprecipitation (RIPA) of the GH/GHBP complex with an anti-GHBP antibody.

Adolescent↗