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K Falk

Publications and source records attributed to K Falk.

At least 19 recordsLinked to original sources
PubMed2006

Orbital angular momentum contribution to the magneto-optical behavior of a binuclear cobalt(II) complex.

We report magnetic and magnetic circular dichroism investigations of a binuclear Co(II) compound. The Hamiltonian of the system involves an isotropic exchange interaction dealing with the real spins of cobalt(II) ions, spin-orbit coupling, and a low-symmetry crystal field acting within the (4)T(1g) ground manifold of each cobalt ion. It is shown that spin-orbit coupling between this ground term and the low-lying excited ones can be taken into consideration as an effective g factor in the Zeeman part of the Hamiltonian. The value of this g factor is estimated for the averaged experimental values of Racah and cubic ligand field parameters for high-spin cobalt(II). The treatment of the Hamiltonian is performed with the use of a irreducible tensor operator technique. The results of the calculation are in good agreement with experimental observations. Both a large effective g factor for the ground state and a large temperature-independent part of the magnetic susceptibility arise because of a strong orbital contribution to the magnetic behavior of the Co(II) dimer.

Circular Dichroism↗
PubMed2006

Longitudinal study of a natural outbreak of heart and skeletal muscle inflammation in Atlantic salmon, Salmo salar L.

Heart and skeletal muscle inflammation (HSMI) is a transmissible disease of farmed Atlantic salmon, Salmo salar L. It is characterized by significant epi-, endo- and myocarditis, as well as myositis, particularly involving red skeletal muscle. The aetiology of HSMI is currently unresolved, though a viral cause is suspected. Since its discovery in 1999, HSMI has become an increasing problem for the Norwegian farming industry, with some farms experiencing yearly outbreaks and subsequent economic losses. In the present study an Atlantic salmon farm was studied from December 2003 to April 2005. Samples from apparently healthy as well as clinically diseased fish were collected monthly and examined histopathologically. The first fish to be diagnosed with HSMI was sampled in May, 8 months after transfer to sea. A clinical outbreak of HSMI followed in June, when all fish in the sample had lesions consistent with HSMI. Subsequent samples revealed that cardiac lesions decreased in severity 2 months after the start of the outbreak, but that multiple foci of cellular infiltration and necrosis persisted throughout the year. There appeared to be a shift in lesion location from being most severe in the compact myocardium in early stages of disease to a greater involvement of the atrium and spongy layer of the ventricle in later samples. Late samples also showed increased fibrosis of cardiac tissue. In conclusion, HSMI appears to be a severe disease with elevated mortality, morbidity close to 100% and prolonged duration.

Animals↗
PubMed2004

Heart and skeletal muscle inflammation in Atlantic salmon, Salmo salar L: a new infectious disease.

Heart and skeletal muscle inflammation (HSMI) is a disease syndrome of unknown aetiology first observed in farmed Atlantic salmon, Salmo salar, in 1999. In the present study we have demonstrated for the first time that HSMI is an infectious disease. It was induced in Atlantic salmon post-smolts after injection with tissue homogenate from farmed Atlantic salmon previously diagnosed with HSMI. The lesions were also induced in cohabitating salmon given a corresponding injection without tissue homogenate. Six weeks post-challenge the fish that had been injected with tissue homogenate developed a serious epicarditis and myocarditis with mononuclear cell infiltrations in compact and spongy layers of the heart. Similar lesions were found in cohabitants after 10 weeks. The lesions were consistent with samples from field outbreaks of HSMI. No lesions were found in control fish. A viral aetiology is strongly suggested, as no difference in disease induction between an inoculum containing antibiotics and a non-treated inoculum was found. Further investigations are required in order to make conclusions regarding the cause and pathogenesis of HSMI.

Animals↗
PubMed2003

Antifibrinolytic proCPU is present in the peritoneal cavity during surgery.

The fibrinolytic capacity of the peritoneum plays a pivotal role in peritoneal wound healing. During surgery the balance between fibrin deposition and degradation is tilted towards deposition, leading to the formation of adhesions. In blood, carboxypeptidase U (CPU) stabilizes clots by retarding fibrinolysis. The purpose of this study was to investigate whether the more stable zymogen, proCPU, is also present in the peritoneal cavity and, if so, to examine its origin. Levels of proCPU were measured in plasma and serosal peritoneal fluid collected during surgery. Peritoneal biopsies were stained for proCPU. Two-dimensional gel electrophoresis was performed to study the protein composition of the serosal fluid compared to plasma and Western blotting to identify differences in glycosylation of proCPU, indicating possible different cellular origin. Cultured human mesothelial cells were examined for proCPU production under normal conditions and conditions mimicking surgery. We found comparable and correlating levels of proCPU in serosal fluid and plasma. ProCPU was also found where fibrin covered the injured peritoneal surface. A protein composition very similar in serosal fluid and plasma was shown by two-dimensional gel electrophoresis, and the proCPU pattern did not indicate a different origin. No proCPU production was found in cultured mesothelial cells. This is the first study to report on the presence of proCPU in the peritoneal cavity, which seems to be the result of plasma oozing out during the inflammatory reaction to the surgical trauma. This is likely to be important for the balance between fibrin deposition and degradation and thereby in the formation of postoperative adhesions.

Antifibrinolytic Agents↗
PubMed2001

IL-3 induces B7.2 (CD86) expression and costimulatory activity in human eosinophils.

Eosinophils in tissues are often present in intimate contact with T cells in allergic and parasitic diseases. Resting eosinophils do not express MHC class II proteins or costimulatory B7 molecules and fail to induce proliferation of T cells to Ags. IL-5 and GM-CSF induce MHC class II and B7 expression on eosinophils and have been reported in some studies to induce eosinophils to present Ag to T cells. The cytokine IL-3, like IL-5 and GM-CSF, is a survival and activating factor for eosinophils and the IL-3 receptor shares with the IL-5 and GM-CSF receptors a common signal transducing beta-chain. IL-3-treated eosinophils expressed HLA-DR and B7.2, but not B7.1 on their surface and supported T cell proliferation in response to the superantigen toxic shock syndrome toxin 1, as well as the proliferation of HLA-DR-restricted tetanus toxoid (TT) and influenza hemagglutinin-specific T cell clones to antigenic peptides. This was inhibited by anti-B7.2 mAb. In contrast, IL-3-treated eosinophils were unable to present native TT Ag to either resting or TT-specific cloned T cells. In parallel experiments, eosinophils treated with IL-5 or GM-CSF were also found to present superantigen and antigenic peptides, but not native Ag, to T cells. These results suggest that eosinophils are deficient in Ag processing and that this deficiency is not overcome by cytokines that signal via the beta-chain. Nevertheless, our findings suggest that eosinophils activated by IL-3 may contribute to T cell activation in allergic and parasitic diseases by presenting superantigens and peptides to T cells.

Antigen-Presenting Cells↗
PubMed2001

Vaccination, prevention, and treatment of experimental autoimmune neuritis (EAN) by an oligomerized T cell epitope.

Using a polypeptide oligomer harboring 16 repeats of the neuritogenic epitope (aa 58-73) of myelin P2 protein separated by spacers, enhancement of the immune response to the P2 protein, an important neuritogenic autoantigen in experimental autoimmune neuritis (EAN), was attempted. In contrast to a previous study with PLP-16-mer antigen-specific response of T cells was attenuated at all doses examined to a variable degree. Treatment of Lewis rats with the P2-16-mer up to 2 months before immunization with P2(53-78) (vaccination) or after immunization but before appearance of disease (prevention) had a strong tolerizing effect against the induction of EAN on immunization with P2(53-78). Moreover, rats injected with 200 microg of the P2-16-mer i.v. on day 11 after disease induction, at which time the initial signs of disease had appeared, were almost completely protected against progression of clinical disease, whereas animals treated with the same amount of monomeric control peptide developed severe disease (treatment). Similar results were obtained by i.v. treatment of adoptive-transfer EAN with the P2-16-mer. The lack of clinical signs of disease after 16-mer therapy could be correlated with a reduced proliferative response of P2(53-78)-specific lymph node cells. The frequency of apoptotic T cells in sciatic nerve or in lymph node cells, however, was not increased by the 16-mer treatment, suggesting that induction of anergy or other forms of peripheral tolerance may be responsible for the effect. Thus, the oligomerized P2 peptide antigen was highly effective in all three treatment modalities examined in this specific autoreactive T cell-mediated immune response.

Animals↗
PubMed2001

Strain variation, based on the hemagglutinin gene, in Norwegian ISA virus isolates collected from 1987 to 2001: indications of recombination.

Infectious salmon anemia (ISA) is caused by a virus that probably belongs to the Orthomyxoviridae and was first recorded in Norway in 1984. The disease has since spread along the Norwegian coast and has later been found in Canada, Scotland, the Faroe Islands, Chile, and the USA. This study presents sequence variation of the hemagglutinin gene from 37 ISA virus isolates, viz. one isolate from Scotland, one from Canada and 35 from Norway. The hemagglutinin gene contains a highly polymorphic region (HPR), which together with the rest of the gene sequence provides a good tool for studies of epizootics. The gene shows temporal and geographical sequence variation, where certain areas are dominated by distinct groups of isolates. Evidence of transmission of ISA virus isolates within and between regions is given. It is suggested that the hemagglutinin gene from different isolates may recombine. Possible recombination sites are found within the HPR and in the 5'-end flanking region close to the HPR.

Anemia↗
PubMed2001

Strong cooperativeness in the mononuclear iron(II) derivative exhibiting an abrupt spin transition above 400 K.

The spin crossover system, [Fe(bzimpy)(2)](ClO(4))(2).0.25H(2)O, was reinvestigated above room temperature (bzimpy = 2,6-bis(benzimidazol-2-yl)pyridine). The system exhibits an abrupt low-spin to high-spin transition at T(c) = 403 K. Liberation of a fractional amount of water does not affect the spin crossover: the system is perfectly reversible with a hysteresis width of DeltaT = 12 K. The existence of the hysteresis at such high temperature determines that the lowest limit of the solid-state cooperativity parameter is J/k > 403 K despite long iron(II) separations (10 A). The high cooperativeness has been assigned to a perfect pi-stacking of the benzimidazole rings in the crystal lattice at a distance as short as 3.6 A. Variable-temperature IR data and the heat capacity measurements match well the magnetic data. The thermodynamic properties are DeltaH = 17 kJ mol(-)(1), DeltaS = 43 J K(-)(1) mol(-)(1), so that the entropy of the spin transition shows a considerable contribution from the molecular vibrations. A theoretical model has been applied in fitting the magnetic data along the whole hysteresis path. A statistical distribution of the cooperativity parameter led to the feature that angled walls of the hysteresis loop are well reproduced.

Journal Article↗
PubMed2001

Phylogenetic analysis of infectious salmon anaemia virus isolates from Norway, Canada and Scotland.

The sequences of gene segments 2 and 8 from 10 different isolates of infectious salmon anaemia virus (ISAV) sampled in Norway, Canada and Scotland between 1987 and 1999 were determined and compared. Pairwise comparisons revealed a high degree of homology between the European isolates, with identities of 98 to 100% for both genes examined. The Canadian isolate showed identities of 84 and 87 to 88% with the European isolates for the nucleotide sequence of segments 2 and 8, respectively. Phylogenetic analyses were performed to establish the interrelationship between the European virus isolates. The evolutionary rate based on 4 Norwegian isolates clustered together in the analysis of segment 2 was calculated to be 0.96 x 10(-3) nucleotides site(-1) yr(-1). On the basis of this mutation rate it was estimated that the Norwegian Glesvaer 90 and Canadian Bay of Fundy 97 isolates diverged around 1900, which coincides with transportation of salmonids between Europe and North America starting in the late nineteenth century.

Amino Acid Sequence↗
PubMed2001

Synthesis of linear and comb-like peptide constructs containing up to four copies of a T cell epitope and their capacity to stimulate T cells.

Polypeptide constructs containing up to four copies of the T cell epitope 306-318 of influenza virus haemagglutinin have been synthesized on solid phase. Between the copies, a non-natural PEG-based spacer amino acid has been introduced. The oligomeric epitopes were analysed by RP-HPLC and ES-MS. The arrangement of the epitopes within the peptide constructs was either linear or comb-like. The proliferative response in a T helper cell assay induced by these oligomerized epitopes has been tested, showing that the linearly arranged epitopes are more effective than the comb-like oligomers.

Amino Acid Sequence↗
PubMed2001

Sodium polyacrylate potentiates the anti-adhesion effect of a cellulose-derived polymer.

Available methods for postoperative adhesion prevention are insufficient. A previous study demonstrated that LM-200, a bioadhesive cellulose derivative was effective in reducing adhesions. Increasing the viscosity of a polymer solution enhances the tissue separating properties. Theoretically, a combination of sodium polyacrylate (PA) and LM-200 would give more viscous solutions than LM-200 alone, and thus be more efficacious. Therefore the efficacy of various combinations of LM-200 and PA was investigated. A lesion was created in the peritoneum of mice. The solutions to be tested, or saline, were given intraperitoneally. One week post-operatively, adhesion formation was quantified and expressed as a percentage of the original lesion covered with adhesions. PA (0.01 and 0.03 wt%) given separately did not differ in adhesion reducing effect from LM-200 (p = 0.3710 and 0.3481) but PA (0.1 wt%) resulted in significantly less adhesion formation (p = 0.0004). The effect of LM-200 increased significantly when adding PA (0.01 wt%) (p = 0.0007) or PA (0.03 wt%) (p < 0.0001). When adding PA (0.1 wt%) the effect was even more pronounced (p < 0.0001). The combination of a bioadhesive cellulose derivative and the polymer PA, was effective in reducing postoperative adhesion formation and a dose-dependent increase in efficacy was obtained compared to using the two components separately.

Abdomen↗
PubMed2001

Reduction of experimental adhesion formation by inhibition of plasminogen activator inhibitor type 1.

BACKGROUND: Adhesion formation is a common cause of complications following surgery. A reduction in peritoneal fibrinolytic capacity during operation is a key mechanism in the early formation of adhesions. An increase in the main inhibitor of fibrinolysis, plasminogen activator inhibitor type 1 (PAI-1), is a major factor in the loss of fibrinolytic activity. The aim of this study was to investigate if inhibition of PAI-1 could reduce the formation of adhesions after surgery. METHODS: Mice (n = 53) were subjected to a standard surgical procedure in order to induce adhesion formation to the abdominal side wall. At the conclusion of the operation, fragments for antigen binding of polyclonal rabbit antibody against PAI-1 (PRAP-1) were injected intraperitoneally, at two different concentrations. Control animals received an equal volume of the vehicle (saline). One week after operation adhesion formation was quantified. RESULTS: Both doses of PRAP-1 significantly reduced adhesion formation compared with the saline control (P = 0.003 and P = 0.002). There were no signs of bleeding in the postoperative period or at reoperation. CONCLUSION: The present observations lend further support to the hypothesis of a pivotal role of fibrinolysis in the early formation of adhesions, and open up new possibilities for adhesion reduction by inhibiting PAI-1.

Animals↗
PubMed2001

Prevention of adhesions by surfactants and cellulose derivatives in mice.

OBJECTIVE: To evaluate the efficacy of hydrophobically modified ethyl (hydroxyethyl) cellulose (cellulose), sodium hyaluronate (hyaluronate) and phosphatidylglycerol, in the reduction of adhesion formation. DESIGN: Controlled study. SETTING: Experimental academic unit, Sweden. MATERIAL: NMRI mice. Solutions: (1) cellulose, (2) hyaluronate, (3) phosphatidylglycerol, (4) phosphatidylglycerol and cellulose, and (5) phosphatidylglycerol, cellulose and hyaluronate. INTERVENTIONS: A standard lesion was created in the parietal peritoneum in mice. One of the viscous solutions to be tested, or saline, was given intraperitoneally. MAIN OUTCOME MEASURES: Amount of adhesions found one week postoperatively. RESULTS: Cellulose; phosphatidylglycerol and cellulose; and phosphatidylglycerol, cellulose and hyaluronate all significantly reduced the amount of adhesions (p=0.0002, p=0.002, p < 0.0001), as did the hyaluronate alone (p < 0.05). Phosphatidylglycerol alone did not reduce the amount of adhesions. Combining cellulose with phosphatidylglycerol, or with hyaluronate, did not improve efficacy. CONCLUSION: Cellulose and hyaluronate were effective in reducing the formation of adhesions. Combining cellulose with hyaluronate or phosphatidylglycerol or both did not improve efficacy.

Animals↗
PubMed2000

[Time delay in the thrombolytic treatment of myocardial infarction].

INTRODUCTION: Thrombolytic treatment is central in the treatment of patients with myocardial infarction. MATERIAL AND METHODS: A cross-sectional study was conducted to determine the time delay incurred in thrombolytic treatment of patients with myocardial infarction in Ostfold Hospital, Fredrikstad, Norway. Over a seven-month period, 317 patients were diagnosed as having myocardial infarction. 80 patients (25%) received thrombolytic therapy, 68 of whom (85%) were eligible for the study. 12 patients were excluded either because of not meeting the inclusion criteria or because of incomplete data. RESULTS: The following median times were recorded: from onset of chest pain till first contact with the health care services, 59 minutes; from first contact till arrival at hospital, 32 minutes; from hospital arrival till initiation of treatment, 40 minutes; from onset of chest pain till initiation of treatment, 147 minutes. 38% of the patients received thrombolysis within 120 minutes of pain onset, and 35% received treatment within 30 minutes of arrival in hospital. There was no difference in time delay before contacting health care services among patients with or without a previous history of coronary heart disease, except for those who took nitroglycerine at onset of symptoms. They had the longest time delay. INTERPRETATION: In order to reduce time delay, doctors should give better instructions to patients with a previous history of coronary heart disease and conduct regular training programmes for hospital interns and nurses. It is further assumed that prehospital ECG and direct admission to the coronary care unit, or initiation of thrombolysis in the emergency department or in the ambulance, would result in a considerable reduction in time delay.

Adult↗
PubMed2000

Induction and suppression of an autoimmune disease by oligomerized T cell epitopes: enhanced in vivo potency of encephalitogenic peptides.

T cell epitope peptides derived from proteolipid protein (PLP139-151) or myelin basic protein (MBP86-100) induce experimental autoimmune encephalomyelitis (EAE) in "susceptible" strains of mice (e.g., SJL/J). In this study, we show that the encephalitogenic effect of these epitopes when injected subcutaneously in complete Freund's adjuvant was significantly enhanced if administered to the animal in a multimerized form as a T cell epitope oligomer (i.e., as multiple repeats of the peptide epitope, such as 16-mers). Oligomer-treated SJL/J mice developed EAE faster and showed a more severe progression of the disease than animals treated with peptide alone. In addition, haplotype-matched B10.S mice, "resistant" to EAE induction by peptide, on injection of 16-mers developed a severe form of EAE. Even more striking, however, was the dramatic suppression of incidence and severity of the disease, seen after single intravenous injections of only 50 microg of the PLP139-151 16-mer, administered to SJL/J mice 7 d after the induction of the disease. Although relapse occurred at about day 45, an additional injection several days before that maintained the suppression. Importantly, the specific suppressive effect of oligomer treatment was also evident if EAE was induced with spinal cord homogenate instead of the single peptide antigen. By contrast, the PLP139-151 peptide accelerated rather than retarded the progression of disease.

Animals↗
PubMed2000

Antigen-specific elimination of T cells induced by oligomerized hemagglutinin (HA) 306-318.

In a previous study we reported that oligomerized T cell epitopes "superactivated" CD4+ T cells. These oligomers, consisting of 12-16 copies of a peptide epitope derived from the hemagglutinin protein of influenza virus (HA306-318), induced a specific T cell response in amounts as little as 5 pg/ml. We now show that the improved antigenicity of these multimerized epitopes can also be utilized to induce "high zone tolerance". Tolerization, similar to activation, occurred at about 3 logs lower concentration of oligomer than of peptide. HA306-318-specific T cell cultures became nonresponsive to stimulation with peptide after incubation with 0.5-5 microg/ml HA306-318 12-mer. The nonresponsiveness was accompanied by a drastic down-regulation of the TCR and by T cell elimination by apoptotic cell death. In contrast, stimulation with peptide even at 50 microg/ml led to temporary induction of anergy. Consequently, induction of tolerance with the oligomer was permanent and no recovery of the cultures was seen in recall experiments 12-14 days after high zone exposure to the 12-mer.

Antigens, Viral↗
PubMed2000

Initial events in infectious salmon anemia virus infection: evidence for the requirement of a low-pH step.

We have investigated the initial steps in the interaction between infectious salmon anemia virus (ISAV) and cultured cells from Atlantic salmon (SHK-1 cell line). Using radioactively or fluorescently labelled viral particles we have studied the binding and fusion kinetics and the effect of pH on binding, uptake, and fusion of ISAV to SHK-1 cells and liposomes. As pH in the medium was reduced from 7.5 to 4.5, the association of virus to the cells was nearly doubled. The same effect of pH was observed when fusion between ISAV and liposomes was analyzed. In addition, the binding of ISAV to intact SHK-1 cells and to cell membrane proteins blotted onto filters was neuraminidase sensitive. However, the increased binding induced by low pH was not neuraminidase sensitive, probably reflecting activation of a fusion peptide at low pH. By using confocal fluorescence microscopy, the increased fusion of fluorescently labelled ISAV with the plasma membrane due to low pH could be demonstrated. When vacuolar pH in the cells was raised during inoculation with chloroquine or ammonium chloride, both electron and confocal microscopy showed accumulation of ISAV in endosomes and lysosomes. Production of infectious virus could be increased by lowering the extracellular pH during infection. Furthermore, chloroquine present during virus inoculation also caused a reduction in the synthesis of viral proteins in ISAV-infected cells as well as in the production of infective virus. These results indicate that ISAV binds to sialic acid residues on the cell surface and that the fusion between virus and cell membrane takes place in the acid environment of endosomes. This provides further evidence for a high degree of similarity between ISAV and influenza virus and extends the basis for the classification of this virus as a member of the Orthomyxoviridae family.

Ammonium Chloride↗