Search PubMed⌕ Search

Biomedical subjects

M Pettersson

Publications and source records attributed to M Pettersson.

At least 19 recordsLinked to original sources
PubMed2005

Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death.

AIMS: Drug-induced QTc-prolongation, resulting from inhibition of HERG potassium channels may lead to serious ventricular arrhythmias and sudden death. We studied the quantitative anti-HERG activity of pro-arrhythmic drugs as a risk factor for this outcome in day-to-day practice. METHODS AND RESULTS: All 284,426 case reports of suspected adverse drug reactions of drugs with known anti-HERG activity received by the International Drug Monitoring Program of the World Health Organization (WHO-UMC) up to the first quarter of 2003, were used to calculate reporting odds ratios (RORs). Cases were defined as reports of cardiac arrest, sudden death, torsade de pointes, ventricular fibrillation, and ventricular tachycardia (n = 5591), and compared with non-cases regarding the anti-HERG activity, defined as the effective therapeutic plasma concentration (ETCPunbound) divided by the HERG IC50 value, of suspected drugs. We identified a significant association of 1.93 (95% CI: 1.89-1.98) between the anti-HERG activity of drugs, measured as log10 (ETCPunbound/IC50), and reporting of serious ventricular arrhythmias and sudden death to the WHO-UMC database. CONCLUSION: Anti-HERG activity is associated with the risk of reports of serious ventricular arrhythmias and sudden death in the WHO-UMC database. These findings are in support of the value of pre-clinical HERG testing to predict pro-arrhythmic effects of medicines.

Adverse Drug Reaction Reporting Systems↗
PubMed2005

Treatment of a patient with a nodal peripheral T-cell lymphoma (angioimmunoblastic T-Cell lymphoma) with a human monoclonal antibody against the CD4 antigen (HuMax-CD4).

A patient with a CD4+ refractory peripheral T-cell lymphoma (PTL), subtype angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment all palpable enlarged lymph nodes disappeared. A decline of normal CD4+ T-cells in the blood mirrored the treatment effect. Shortly after stopping treatment the patient relapsed with new enlarged lymph nodes. This time no antitumor effect was seen when HuMax-CD4 treatment was reinstituted. No severe side effects were observed during the antibody treatment. This case report is the first describing that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to study further in patients with CD4+ PTL.

Aged↗
PubMed2004

Rotational isomerism of acetic acid isolated in rare-gas matrices: Effect of medium and isotopic substitution on IR-induced isomerization quantum yield and cis-->trans tunneling rate.

Rotational isomerization of acetic acid (CH3COOH) is studied in Ar, Kr, and Xe matrices. The light-induced trans-->cis reaction is promoted using resonant excitation of a number of modes in the 3500-7000 cm(-1) region, and the quantum yields for this process are measured for various acetic acid isotopologues and matrix materials. For excitation of acetic acid at energies above the predicted isomerization energy barrier (> or =4400 cm(-1)), the measured quantum yields are in average 2%-3%, and this is one order of magnitude smaller than the corresponding values known for formic acid (HCOOH). This difference is interpreted in terms of the presence of the methyl group in acetic acid, which enhances energy relaxation channels competing with the rotational isomerization. This picture is supported by the observed large effect of deuteration of the methyl group on the photoisomerization quantum yield. The trans-->cis reaction quantum yields are found to be similar for Ar, Kr, and Xe matrices, suggesting similar energy relaxation processes for this molecule in the various matrices. The IR-induced cis-->trans process, studied for acetic acid deuterated in the hydroxyl group, shows reliably larger quantum yields as compared with the trans-->cis process. For pumping of acetic acid at energies below the predicted isomerization barrier, the trans-->cis reaction quantum yields decrease strongly when the photon energy decreases, and tunneling is the most probable mechanism for this process. For the cis-->trans dark reaction, the observed temperature and medium effects indicate the participation of the lattice phonons in the tunneling-induced process.

Journal Article↗
PubMed2004

Association between low Apgar score and neonatal cholestasis.

AIM: To investigate the association between low Apgar score and the development of cholestasis. METHODS: Seventy-seven cholestatic infants, all referred to our tertiary centre and born between 1987 and 1996 were studied. Twenty-eight patients had biliary atresia (BA), 36 had various intrahepatic disorders and for 13 patients the aetiology of the cholestasis was unknown. Data on gestational age, mode of delivery, Apgar score and birthweight for the cholestatic infants and 1,118,270 control subjects born during the same time period were obtained from the Swedish Medical Birth Registry. If the Apgar score of the cholestatic patient was <7 at 1 min and/or <9 at 5 min and/or <9 at 10 min of age the available medical records were reviewed for signs of neonatal distress. RESULTS: Five cholestatic patients, all of them premature, fulfilled the Apgar criteria. For two of them the low Apgar score and need for immediate resuscitation were explained by major surgical problems. The other three patients, two with biliary atresia (BA) and one with Alagille syndrome, had clinical signs of neonatal distress. The incidence of low Apgar score in BA patients was 7% and in cholestatic patients without known aetiology 0%, neither figure differing significantly from that of the of the control group (2.6%). CONCLUSION: Low Apgar score is not more common in any of the cholestatic groups than in the general Swedish population of newborns. We suggest that aetiological associations other than low Apgar score need to be considered in infants with cholestasis of unknown cause.

Apgar Score↗
PubMed2003

The rate of change of a soil bacterial community after liming as a function of temperature.

The response of a bacterial community to liming of a forest humus soil (pH 4.9 increased to pH 7.5) was studied in the laboratory at three temperatures (5, 20, and 30 degrees C). As a comparison an unlimed soil (pH 4.9) and a soil limed in the field 15 years ago (pH around 6) were also included. The bacterial community tolerance of pH was measured using TdR incorporation. The pH of the bacterial suspensions (bacteria directly extracted from soil) was altered to 3.6 and 8.3 using different buffers before measuring TdR incorporation. The logarithmic ratio between TdR incorporation at 8.3 and 3.6 was then used as an indicator of the community pH tolerance. The rate of changes in the community tolerance to pH after liming was fastest for the soil incubated at 30 degrees C, but only minor differences in rate of change could be seen between samples incubated at 5 and 20 degrees C. Changes in phospholipid fatty acid (PLFA) pattern after increasing the pH were most rapid for the bacterial community in the soil incubated at 30 degrees C followed by the soil incubated at 20 degrees C, whereas no changes could be seen in the PLFA pattern of the soil incubated at 5 degrees C, even after 82 days' incubation. Thus, the changes in the PLFA pattern were considerably slower than the changes in bacterial community tolerance to pH measured using TdR incorporation.

Adaptation, Physiological↗
PubMed2001

Matrix isolation and ab initio study of the hydrogen-bonded H2O2-CO complex.

The structure, energetics, and infrared spectrum of the H2O2-CO complex have been studied computationally with the use of ab initio calculations and experimentally by FTIR matrix isolation techniques. Computations predict two stable conformations for the H2O2-CO complex, both of which show almost linear hydrogen bonds between the subunits. The carbon-attached HOOH-CO complex is the lower-energy form, and it has an interaction energy of -9.0 kJmol(-1) at the CCSD(T)/6-311++G(3df,3pd)// MP2/6-311++G(3df,3pd) level. The higher-energy form, HOOH-OC, has an interaction energy of 4.7 kJmol(-1) at the same level of theory. Experimentally, only the lower-energy form, HOOH-CO, was observed in Ar, Kr, and Xe matrices, and the hydrogen bonding results in substantial perturbations of the observed vibrational modes of both complex subunits. UV photolysis of the complex species primarily produces a complex between water and carbon dioxide, but minor amounts of HCO and trans-HOCO were found as well.

Journal Article↗
PubMed2001

Distinct and regulated expression of Notch receptors in hematopoietic lineages and during myeloid differentiation.

Hematopoietic development is a delicate balance of cell fate decisions in multipotent cells between self-renewal and differentiation. In multiple developmental systems, the Notch receptors are important factors regulating these processes. Hematopoietic progenitor cells have been shown to express Notch1, and studies with an activated intracellular form has revealed a functional role. To assess the function of other Notch members in hematopoiesis, we investigated the expression pattern of Notch1, Notch2, and Notch3 in hematopoietic lineages at the level of RNA and protein. We demonstrate that Notch1 and Notch2 are expressed in multiple lineages, and that Notch1 in particular appears to be regulated during myeloid differentiation. Notch1 was up-regulated and expressed at high levels in adherent macrophages. Mast cells expressed only low levels of Notch1 mRNA whereas Notch2 mRNA was highly expressed. In addition we could detect Notch3 mRNA and protein in cell lines representing mast cell progenitors. These expression patterns imply that the different Notch genes may have very distinct functions during hematopoiesis, and that Notch3 could be a specific regulator of mast cell development. The finding that Notch1 was up-regulated in the adherent cells developing from a multipotent progenitor cell line suggests that this protein may posses dual functions in hematopoiesis, i.e. at the stage of cell fate decision, and at the maturation stage of monocytes when adhesion to the specific microenvironment is accomplished.

Animals↗
PubMed2000

Characterization, chromosomal localization, and expression during hematopoietic differentiation of the gene encoding Arl6ip, ADP-ribosylation-like factor-6 interacting protein (ARL6).

Proliferation and differentiation of hematopoietic stem cells and progenitors are regulated by signals from the microenvironment, involving both secreted cytokines and adhesion molecules. The exact mechanisms by which cytokines act on hematopoietic development are still not well understood. To extend the molecular characterization of gene regulation during cytokine-induced hematopoiesis, we applied mRNA differential display to identify genes regulated when multipotent progenitor cells are allowed to differentiate into monocytes and neutrophils. Here we report the isolation and characterization of a gene that is downregulated during myeloid differentiation and encodes a 23-kDa protein with four putative transmembrane segments. The gene, which we named Arl6ip, is identical to a mouse gene recently identified by its physical interaction with ADP-ribosylation-like factor-6 (ARL6), belonging to the Ras superfamily. We add information on its full-length characterization as well as its regulation during hematopoiesis. It is expressed in all hematopoietic cell lineages, but the highest level of expression is found in early myeloid progenitor cells. Preliminary studies by immunofluorescence microscopy revealed that the ARL6IP protein is predominantly localized to intracytoplasmic membranes. This suggests an involvement of the Arl6ip gene in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A stable argon compound

The noble gases have a particularly stable electronic configuration, comprising fully filled s and p valence orbitals. This makes these elements relatively non-reactive, and they exist at room temperature as monatomic gases. Pauling predicted in 1933 that the heavier noble gases, whose valence electrons are screened by core electrons and thus less strongly bound, could form stable molecules. This prediction was verified in 1962 by the preparation of xenon hexafluoroplatinate, XePtF6, the first compound to contain a noble-gas atom. Since then, a range of different compounds containing radon, xenon and krypton have been theoretically anticipated and prepared. Although the lighter noble gases neon, helium and argon are also expected to be reactive under suitable conditions, they remain the last three long-lived elements of the periodic table for which no stable compound is known. Here we report that the photolysis of hydrogen fluoride in a solid argon matrix leads to the formation of argon fluorohydride (HArF), which we have identified by probing the shift in the position of vibrational bands on isotopic substitution using infrared spectroscopy. Extensive ab initio calculations indicate that HArF is intrinsically stable, owing to significant ionic and covalent contributions to its bonding, thus confirming computational predictions that argon should form a stable hydride species with properties similar to those of the analogous xenon and krypton compounds reported before.

Journal Article↗
PubMed2000

Isolation of MYADM, a novel hematopoietic-associated marker gene expressed in multipotent progenitor cells and up-regulated during myeloid differentiation.

A large number of hematopoietic cytokines and their receptors as well as transcription factors have been shown to be involved in maturation of blood cells. However, many of the genes important for the differentiation of multipotent stem cells to specific cellular lineages are still unknown. To identify novel genes involved in lineage selection of myeloid cells, we have applied differential display analysis during commitment toward granulocytes and macrophages of an IL-3-dependent multipotent progenitor cell line, FDCP-mix. One regulated cDNA represented a novel gene with restricted expression pattern within the hematopoietic system and was strongly up-regulated when FDCP-mix cells differentiated in GM-CSF, G-CSF, and M-CSF. The expression appears to be differentiation stage-specific in myeloid cells and is absent in B and T lymphocytes. Thus we found expression in normal mouse bone marrow enriched for stem cells and multipotent progenitors (c-kit+Sca-1+Lin- cells). When these cells were induced to differentiate toward myeloid cells, MYADM was up-regulated. In contrast, during conditions known to favor the development of B cell progenitors, the gene was down-regulated. The gene, termed MYADM for myeloid-associated differentiation marker gene, shows 100% identity to expressed sequence tags from early mouse embryonic development as well as from the mouse lung and from activated mouse macrophages. The predicted 32-kDa MYADM protein contains multiple hydrophobic putative transmembrane segments and has several potential consensus sites for phosphorylation. In view of its expression pattern, MYADM could serve as a new marker gene for hematopoietic differentiation. Although the function is unknown, antisense oligonucleotides were able to inhibit colony formation of c-kit+ Lin- bone marrow cells, suggesting an important role for MYADM in myeloid differentiation.

Amino Acid Sequence↗
PubMed2000

Vibrational Spectra of cis and trans Oxalyl Fluoride and Their Site-Selective IR-Induced Rotamerization in an Argon Matrix.

A cis/trans equilibrium mixture of matrix-isolated oxalyl fluoride was irradiated with a narrowband tunable IR source in the 2nu (CO) spectral region (3680-3710 cm(-1)). Rotamerization of cis into trans and vice versa was achieved (even site selective) by selective IR pumping. The experiments strongly aided a detailed IR analysis of both rotamers. For a complete vibrational analysis, low-temperature Raman measurements were also performed. With the exception of the torsional vibration of cis oxalyl fluoride, all the fundamentals of both rotamers have been observed. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Computer experiments on xenon-containing molecules

Quantum chemical calculations have been performed on xenon-containing rare gas molecules. The novel HXeY molecules are best characterised as HXe+Y- where Y can be at least H, Cl, Br, I, CN, SH, OH or NCO. A good agreement of MP2/LJ18/6-311 + + G(2d,2p) results is obtained with respect to the trend in experimental data for the Xe-H stretching wavenumbers of the HXeY molecules. Predictions concerning compounds between Xe and carboxylic acids are made. It is shown that Xe can bind to the carboxy group of the side chains of amino acids, thus, allowing in principle Xe to bind to proteins.

Journal Article↗
PubMed1999

The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.

Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis.

Amino Acid Sequence↗
PubMed1997

Simple and sensitive method for determination of nicotine in plasma by gas chromatography.

Smoking and other forms of nicotine consumption are among the most important risk factors for cardiovascular disease and cancer. Many of the cessation therapies require administration of nicotine. Accordingly, precision analysis for nicotine in plasma has become increasingly important. Several of the recently published methods require elaborate sample handling and/or processing. We report a simple, rapid and reliable gas chromatography method with a high sensitivity for determination of unchanged nicotine in plasma, which can be used in the processing and quantification of large series of nicotine samples, e.g., in clinical trials of nicotine-based smoking or tobacco cessation drug delivery systems.

Chromatography, Gas↗
PubMed1997

Withdrawal reactions with selective serotonin re-uptake inhibitors as reported to the WHO system.

OBJECTIVE: The present study was performed both to investigate whether there might be a difference between the selective serotonin re-uptake inhibitors, (SSRIs) with regard to the incidence of withdrawal reactions, and to describe the associated symptoms. From the WHO database, therefore, all case reports from the year of introduction for each of the SSRIs, fluoxetine, paroxetine and sertraline, were retrieved. Sales figures were obtained from Intercontinental Medical Statistics International. The reporting rates were calculated as the number of reports per million defined daily doses (DDDs) sold per year. RESULTS: The reporting rate of withdrawal reactions for paroxetine was found to be higher than that for sertraline and fluoxetine in each of the countries selected for detailed analyses (US, UK and Australia), as well as for all 16 countries combined. Moreover, using the WHO system of organ classification, the ratio of central nervous system to psychiatric withdrawal symptoms was 1.9 and 2.1 for paroxetine and sertraline, respectively, whereas that for fluoxetine was 0.48, indicating a possible qualitative difference between the SSRIs with respect to the nature of the withdrawal syndrome.

1-Naphthylamine↗
PubMed1997

How does cystitis affect a comparative risk profile of tiaprofenic acid with other non-steroidal antiinflammatory drugs? An international study based on spontaneous reports and drug usage data. ADR Signals Analysis Project (ASAP) Team.

Series of well-documented case reports strongly suggest a causal association between tiaprofenic acid and a form of aseptic cystitis, which can cause serious and long-term morbidity if the drug is not withdrawn promptly. These findings are supported in the Australian and UK spontaneous reporting data-bases. Using sales data as the denominator, a comparison of NSAIDs in the WHO drug monitoring data-base indicates that the reaction is specific to tiaprofenic acid and cannot be accounted for by changes in reporting patterns in certain countries or years. Delayed recognition is an important feature of this reaction and possible reasons for this are discussed. Comparison of the risk profiles of seven NSAIDs indicated that tiaprofenic acid had the poorest risk profile, compared with NSAIDs of similar efficacy, when cystitis reports were included. The results suggest that combining spontaneous reports, classified according to severity, with sales data may enhance the ability of drug monitoring data-bases to contribute to risk benefit appraisals.

Anti-Inflammatory Agents, Non-Steroidal↗