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K Christiansen

Publications and source records attributed to K Christiansen.

At least 37 records · Page 2Linked to original sources

Preliminary estimates of the direct costs associated with endemic diseases of livestock in Great Britain.

Many 'economic' studies of livestock diseases in Great Britain have been carried out over time. Most studies have considered just one or two diseases and used a different methodology and valuation base from other studies, hampering any comparative assessment of the economic impact of diseases. A standardized methodology was applied to the estimation of the direct costs to livestock production of some 30 endemic diseases/conditions of farm animals in Great Britain. This involved identification of the livestock populations at risk, estimation of the annual incidence of each disease in these populations, identification of the range and incidence of physical effects of each disease on production, valuation of the physical effects of each disease and estimation of the financial value of output losses/resource wastage due to a disease and the costs of specific treatment and prevention measures. The wider economic impacts of disease (such as the implications for human health, animal welfare and markets) were not included in the assessments. Using this standardized methodology with common financial values, a simple spreadsheet model was constructed for each disease. Given the paucity of appropriate disease data for economic assessment, 'low' and 'high' values were used to reflect uncertainties surrounding key disease parameters. Preliminary estimates of the value of disease output losses/resource wastage, treatment and prevention costs are presented for each disease. Despite the limitations of the spreadsheet models and of the estimates derived from them, we conclude that the models represent a useful start in developing a system for the comparative economic assessment of livestock diseases in Great Britain.

Animals↗

Involvement of PI 3-kinase and activated ERK in facilitating insulin-stimulated triacylglycerol synthesis in hepatocytes.

Triacylglycerol synthesis was studied in hepatocytes isolated from fasted/refed rats by EDTA perfusion. Insulin induced a 1.5-fold increase in glucose incorporation into triacylglycerol. Insulin-stimulated triacylglycerol synthesis and insulin-stimulated protein kinase B/Akt activity were inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY 294002, and the mitogen-activated protein kinase kinase inhibitor PD 98059. Inhibition of p70 ribosomal protein-S6 kinase with rapamycin was without effect. Insulin-stimulated pyruvate dehydrogenase activity was abolished by phosphatidylinositol 3-kinase inhibitors. No effect of insulin on acetyl CoA carboxylase activity was observed.

Acetyl-CoA Carboxylase↗

Fusidic acid adverse drug reactions.

Unlike trials conducted today on new antimicrobials, the introduction of fusidic acid was not accompanied by extensive studies on toxicity and side effects. The early studies on small numbers of patients reported fusidic acid to be a nontoxic drug with the main side effects being gastrointestinal tract discomfort, diarrhoea and headache. Case reports of hepatotoxicity were reported from 1972. A retrospective analysis showed this to be reversible and mainly associated with intravenous administration. Rarely reported side effects are granulocytopenia, thrombocytopenia and venous spasm. Skin reactions, including contact dermatitis, are uncommon. After many years of use the most common side effects reported for fusidic acid are minor and relate to the gastrointestinal tract.

Acute Kidney Injury↗

Fusidic acid non-antibacterial activity.

In 1978 the first report was published indicating that fusidic acid had an immunomodulatory effect. This study describing an in vitro effect on white cells was followed by an in vivo study showing improved survival in heart transplanted mice. In 1990 these immunomodulatory effects were shown to be related to suppression of cytokine production in animal models of septic shock and insulin dependent diabetes. Disease modulation has been investigated in a number of immunologically mediated diseases, HIV infection, Behcet's disease, Crohn's disease, uveitis and scleroderma. However whether fusidic acid has any useful function as an immunomodulating agent has yet to be fully explored.

Acquired Immunodeficiency Syndrome↗

Are new antibiotics on the horizon?

BACKGROUND: The development of new antimicrobials is driven by the emergence of resistant bacteria, a change in disease pattern such as that caused by opportunistic and nosocomial infections and a need for improved pharmacokinetics or reduced adverse reactions. OBJECTIVE: This article looks at the emerging resistances of significance in the 1990s and then at the new antibiotics that are either to be released or are under development. DISCUSSION: Although some of these antibiotics show great promise, their long term value will ultimately be determined by how appropriately they are used by the medical community.

Anti-Bacterial Agents↗

Levels of prothrombin activation peptide F1+2 in patients with a bleeding tendency.

Numerous recent publications point to significant improvements in haemostasis in the bleeding patient suffering from haemophilia with inhibitors when a recombinant activated factor VII (rFVIIa) molecule is administered in high doses. In theory, activated factor VII (FVIIa) is believed to initiate haemostasis through its physiological interaction with tissue factor at sites of cellular injury, whereby factor X (FX) activation and, in consequence, thrombin formation is amplified. There has been speculation, however, whether high circulating FVII procoagulant (FVII:C) levels may induce systemic coagulation activation. The present retrospective investigation was undertaken to study, ex vivo, the influence of treatment with rFVIIa as assessed by the sensitive marker of prothrombin conversion, prothrombin fragment F1+2, in plasma samples. Study subjects consisted of: seven people suffering from thrombocytopenia participating in a study of the influence of rFVIIa on the bleeding time, in whom serial plasma samples had been collected before and subsequently at 10, 60 and 180 min after infusion of rFVIIa; four haemophilia A patients with inhibitors to FVIII undergoing surgery; two haemophilia A patients with inhibitors treated with rFVIIa for minor bleedings on 16 occasions in whom plasma samples had been collected before and 10-15 min after rFVIIa infusion; and two FVII-deficient patients undergoing treatment with rFVIIa. A group of seven haemophilia A patients with no signs of inhibitors subjected to a pharmacokinetic study of a plasma-derived FVIII concentrate served as controls. In the group of thrombocytopenic patients our results showed a mean increase in F1+2 following doses of 50 microg/kg body weight and 100 microg/kg body weight of rFVIIa of 1.1 and 1.4 nmol/l, respectively, with a gradual increase over time, but there was no significant correlation between FVII:C and the corresponding values of F1+2. During and after haemophilic inhibitor surgery, a mean increase in F1+2 of 1.44 nmol/l (range 0.6-3.2 nmol/l) was found, whereas 16 matched samples collected during treatment for minor bleedings showed a mean increase in F1+2 of 0.10 nmol/l (range -0.12 to 0.20 nmol/l). In FVII-deficient individuals, the mean rise in F1+2 was <0.10 nmol/l. In the control group, the mean elevation of F1+2 was 0.13 nmol/l (range -0.5 to 0.7 nmol/l). Hence, our results show that only discrete changes in F1+2 follow administration of rFVIIa.

Adult↗

Insulin stimulated glycogen synthesis in isolated rat hepatocytes: effect of protein kinase inhibitors.

Glycogen synthesis was studied in rat hepatocytes isolated by EDTA perfusion. Insulin induced a one and a half to twofold increase in glucose incorporation into glycogen. Insulin stimulated glycogen synthesis was inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin (IC50 approximately 40 nM) and LY 294002 (IC50 approximately 20 microM) and the mitogen-activated protein kinase kinase inhibitor PD 98059 (IC50 approximately 40 microM). Wortmannin was without appreciable effect on non-insulin stimulated glycogen synthesis, while LY 294002 and PD 98059 also inhibited the non-insulin stimulated glycogen synthesis. Rapamycin, an inhibitor of p70 ribosomal protein-S6 kinase, was without effect on glycogen synthesis regardless of insulin stimulation.

Androstadienes↗

Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery.

Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group and the control group regarding the expression of adhesion molecules or the oxidative burst activity. In the steroid group the fluid gain during extracorporeal circulation (ECC) was 683 ml (median) compared to 1488 ml in the control group. Steroids prevented hyperthermia in the postoperative period but did not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity or the expression of adhesion molecules on granulocytes following CPB.

Capillary Leak Syndrome↗

Genetic study of African populations: polymorphisms of the plasma proteins TF, PL, F13B, and AHSG in populations of Namibia and Mozambique.

Genetic variations of four highly polymorphic serum proteins, TF, PI, F13B, and AHSG, were tested to distinguish one black African and one Khoisan population of southwest Africa. The results show that indeed the systems TF, PI, and AHSG are of high value for anthropological genetics: The allele frequencies for these systems enable clear identification of and distinction between black African and Khoisan populations. The F13B locus, on the other hand, reveals for both the black African and the Khoisan populations specific and unique African variants: a high frequency of F13B*2 and the lowest frequency of F13B*3 so far worldwide. The new data are compared with results for TF and PI in another black African population of Mozambique, which Rodewald et al. (1988) had studied previously. The dendrogram, based on genetic distance data D and average linkage cluster analysis, shows minimal distance between both black African populations of Namibia and Mozambique and marked distance between those and the Khoisan population of Namibia.

Alleles↗

Subjective assessment of sitting comfort.

Experts in ergonomics research on sitting comfort recommend a number of so-called objective assessment techniques as well as subjective judgements in order to select the best seat for a given purpose and a defined group of future users. In this paper, a variety of subjective evaluation methods such as general comfort rating, body area comfort rating, chair feature checklists, and direct ranking ranking of chairs are presented, and their pros and cons are discussed.

Consumer Behavior↗

The effect of camptothecin on topoisomerase I catalysis.

The existence of a covalent intermediate in topoisomerase I catalysis allows uncoupling of the cleavage and ligation half-reactions on partially single-stranded DNA substrates containing a highly preferred interaction site. Using this model DNA substrate system we have demonstrated that the cleavage reaction requires bipartite interaction with two distinct DNA duplex regions; One located around the cleavage site (region A) and another located on the side holding the 5'-OH end generated by cleavage (region B). The postcleavage complexes containing the enzyme covalently attached at an internal position are capable of ligating DNA strands matching the noncleaved strand. Previously, we have characterized the effect of the antitumor agent camptothecin on the two half-reactions of topoisomerase I catalysis on DNA substrates allowing bipartite DNA interaction. The obtained results demonstrated that the drug only inhibited the ligation reaction leaving the cleavage reaction unaffected at the studied site. Here, we report that camptothecin also impairs ligation of the cleaved strand to a dinucleotide within region A in the absence of additional DNA contacts. When these results are taken together with the observation that camptothecin-trapped topoisomerase I-DNA complexes preferentially are generated at sites containing guanine immediately 3' to the cleavage position, it suggests that camptothecin inhibits the ligation reaction by forming a reversible ternary complex with the enzyme and DNA at the cleavage site within region A.

Antineoplastic Agents, Phytogenic↗

Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I.

Topoisomerases are involved in many aspects of DNA metabolism such as replication and transcription reactions. Camptothecins, which stabilize the covalent intermediate of topoisomerase I and DNA are effective, though toxic, drugs for cancer therapy. In this study, a new class of topoisomerase I inhibitors was identified, and their mode of action was characterized using recombinant human topoisomerase I preparations and human HL-60 leukemic cells. Quercetin and the related natural flavones, acacetin, apigenin, kaempferol, and morin, inhibit topoisomerase I-catalyzed DNA religation. In contrast to camptothecin, these compounds do not act directly on the catalytic intermediate and also do not interfere with DNA cleavage. However, formation of a ternary complex with topoisomerase I and DNA during the cleavage reaction inhibits the following DNA religation step. 3,3',4',7-Tetrahydroxy-substituted flavones stabilize the covalent topoisomerase I-DNA intermediate most efficiently. Enhanced formation of covalent topoisomerase I-DNA complexes was also demonstrated in human HL-60 cells. In contrast, synthetic 3,5'-dibromo- 4'-hydroxy-3-methylflavones bind selectively to topoisomerase I in its non-DNA-bound form and block the following DNA binding step. As a consequence, these synthetic flavonoids are capable of counteracting topoisomerase I-directed effects of camptothecin. Inhibition of DNA binding is obtained by voluminous hydrophobic substituents in 6-position of the flavone structure. Our data show that selective inhibitors of both half-reactions of topoisomerase I can be derived from the flavone structure.

Base Sequence↗

The distribution of plasminogen (PLG) polymorphism in the Namibian !Kung San and Kavango populations.

Genetic polymorphism of the PLG serum protein was examined in the Namibian !Kung San and Kavango (Bantu) populations by means of IEF technique. The two samples revealed very similar allele frequencies (!Kung San: PLG*A = 0.8351, PLG*B = 0.1649; Kavango: PLG*A = 0.8228, PLG*B = 0.1732 and PLG*M4 = 0.004). The Namibian distributions were within previously observed African PLG ranges. The effects of natural selection were also discussed.

Adult↗

The subcellular localization of newly synthesized cytochrome b5.

The fate of newly synthesized cytochrome b5 was studied in rat hepatocytes. Using an antibody specific for microsomal cytochrome b5, we found newly synthesized microsomal cytochrome b5 in both mitochondria and a mitochondria associated membrane fraction as well as in microsomes. Newly synthesized cytochrome b5 was quickly removed from the site of synthesis on free ribosomes and inserted into membranes at random. No migration of newly synthesized cytochrome b5 between cellular compartments was observed and therefore the assembly of the apoprotein with the heme moiety is apparently not taking place in any particular cellular compartment.

Animals↗

Insertion of functional intact insulin receptors into hepatocytes.

Isolated insulin receptors were inserted into hepatocytes by fusion with receptor-lysophospholipid micelles. The number of receptors was increased approximately two times as monitored by insulin binding experiments. Addition of exogenous receptors resulted in increased receptor autophosphorylation. The exogenous added receptors could be coupled to the intracellular effector system as shown by increased phosphorylation of the insulin receptor substrate 1, IRS-1, and by increased glycogen synthesis. The co-incorporated lysophospholipid was partly metabolized to phospholipid. This method for introducing insulin receptors into cells represents a novel system to study the pathway of insulin signalling and may provide information as to the role of variation of receptor number in insulin action in cellular metabolism of specific cells.

Animals↗

Use of a multiplex PCR to detect and identify Mycobacterium avium and M. intracellulare in blood culture fluids of AIDS patients.

The presence of mycobacteria in blood culture fluids (BACTEC) of AIDS patients with positive growth indices (GIs, > 20 U) was investigated by using a multiplex PCR to detect and identify members of the genus Mycobacterium, M. avium, M. intracellulare, and M. tuberculosis. Three different methods of extracting mycobacterial DNA from blood culture fluid were compared for use with the multiplex PCR. Mycobacterial cells were pelleted from a small aliquot of blood culture fluid by centrifugation, and the DNA was extracted from cells by heat lysis or a sodium iodide-isopropanol or a phenol-chloroform method. DNAs of different sizes were amplified from a region of the MPB70 gene of M. tuberculosis (372 bp) and from a region of the 16S rRNA gene of members of the genus Mycobacterium (1,030 bp), M. intracellulare (850 bp), or M. avium (180 bp) as a multiplex PCR in a single tube. The amplified DNA products were detected by agarose gel electrophoresis and ethidium bromide staining in all 41 (100%) positive cultures after sodium iodide-isopropanol extraction, in 18 (44%) after heat lysis, and in 5 (12%) after phenol-chloroform extraction. Of the 41 positive cultures, 38 were identified as M. avium and 2 were identified as M. intracellulare by both routine methods and multiplex PCR. The remaining mycobacterium was identified as M. intracellulare by routine methods and as M. avium by the multiplex PCR. Another six blood cultures that were negative for the presence of acid-fast bacilli after Ziehl-Neelson staining were also negative by PCR. The study shows that the multiplex PCR is a useful method for the detection and identification of either M. avium or M. intracellulare in small samples of cultured BACTEC 13A fluid with positive GIs ranging from 21 to 999 U. The average time to positive GI was 18 days (median, 13 days) and ranged between 8 and 42 days. The multiplex PCR may permit cultured mycobacteria to be identified at an earlier stage than the routine methods which have been adapted for use with the BACTEC system. The results also show that the method selected for extracting mycobacterial DNA from blood culture fluids is crucial for providing sensitive and accurate PCR results.

AIDS-Related Opportunistic Infections↗

HP and GC subtype distribution in the !Kung San and Kavango in Namibia.

The distribution of the HP and GC serum protein polymorphisms in the !Kung San and Kavango (Bantu) populations in Namibia were examined. The obtained allele frequencies of GC marker system were very similar in both populations (GC*1F approximately equal to 0.80, GC*2 approximately equal to 0.10), while the distributions of the HP subtypes in the !Kung San sample (HP*1F = 0.0967, HP*1S = -.1452, HP*2FS = 0.7581) differed markedly from those in the Kavango one (HP*1F = 0.3791, HP*1S = 0.2375, HP*2S = 0.375). These results confirm previously reported allelic distributions in ethnically similar populations.

Adult↗