A more stable configuration of HArF in solid argon.
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Journal Article↗
Biomedical subjects
M Pettersson
Publications and source records attributed to M Pettersson.
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↗
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↗
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↗
[Temperature measurements in health care--a question of quality assurance].
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Body Temperature↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
[Head of the WHO declares war against mental illness].
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Global Health↗
Prognostic significance of proliferative and apoptotic fractions in low grade follicle center cell-derived non-Hodgkin's lymphomas.
BACKGROUND: The biologic parameters, DNA ploidy and proliferative activity, have been suggested as prognostic factors in non-Hodgkin's lymphoma (NHL). However, reports on the prognostic importance of these factors in follicle center cell-derived (FCC) centroblastic/centrocytic (CB/CC) NHL patients with long follow-up are scarce. METHODS: Apoptotic fractions were quantified in 60 patients with CB/CC NHL by in situ labeling of DNA strand breaks in nuclei [TdT-mediated dUTP/dATP in situ 3'OH--end labeling (TUNEL)]. The findings were related to S-phase and MIB-1 counts, DNA ploidy, and clinical outcome. RESULTS: In CB/CC NHL, the percentages of proliferating and apoptotic cells were lower than in reactive germinal centers (GC; P < 0.05; mean, 0.188 vs 3.263% and 19.05 vs. 69.4% for TUNEL and MIB-1 positive cells in CB/CC and GC, respectively). Significantly higher percentages of MIB-1 and TUNEL positive cells were observed in patients with complete remission when compared with the partial remission / no response group (P < 0.01). The size of proliferative and apoptotic fractions did not correlate with the overall survival of the patients. However, follicular and diffuse growth pattern, elevated serum lactic dehydrogenase, advanced stage, and age indicated a lower probability of 5- and 10-year survival. CONCLUSIONS: The investigation of proliferative and apoptotic fractions in FCC lymphomas may help to define groups of patients to who would benefit from aggressive, high dose therapy protocols and patients to whom less aggressive strategies can be applied safely.
Adult↗
Amniotic fluid antibacterial activity and nutritional parameters in term Mozambican and Swedish pregnant women.
Randomly selected parturients with term singleton pregnancies from two different settings, 83 from Mozambique and 90 from Sweden, entered the study. All of them underwent elective cesarean section, which enabled sterile harvesting of amniotic fluid (AF). AF samples were then tested for antibacterial activity (ABA). Background data and nutritional status were compared. Average age was 32.7 and 30.7 years (n.s.), average parity 6.6 and 1.6 (p < 0.0001), average number of antenatal visits 4.9 and 11.6 (p < 0.0001), and average birthweight 3,194 and 3,688 g (p < 0.01), respectively. Body mass index, mid-upper-arm circumference and hemoglobin did not show any significant differences. The average ABA of AF was more than 50% higher in Swedish than in Mozambican specimens (p < 0.0001). Less than one-sixth of MoZambican women reached the average ABA of AF from Swedish women. Bacterial outgrowth delay equal to or above 3 h was encountered in 13% of Mozambican AF as against 61% of Swedish AF (OR 0.10; 95% CI 0.05-0.19). Histopathological examinations of the placenta, nonplacental membranes and umbilical cord showed inflammatory lesions in 29% of the Mozambican parturients and in 13% of Swedish parurients (OR 2.65; 95% 1.00-6.98). It is probable that the lower antibacterial activity in Mozambican AFs reflects an increased vulnerability to ascending genital infections during late pregnancy.
Adolescent↗
Amniotic fluid interleukins in Swedish and Mozambican pregnant women.
The aim of the study was to investigate inflammatory cytokines, interleukin-1 beta (IL-1 beta), interleukin-1 receptor antagonist (IL-1ra), IL-6, IL-8 in amniotic fluid, in a cohort of Swedish pregnant women from early to late pregnancy and Mozambican late pregnant women with and without signs of histologic chorioamnionitis. Eleven Swedish women were studied from early pregnancy (week 16-17) to late pregnancy (week 37-38). Amniotic fluid was collected via amniocentesis in early pregnancy and also in late pregnancy during elective Caesarean section. From Mozambican women, amniotic fluid was harvested transmurally through the uterus wall during elective Caesarean section. Half of the group of 30 women showed histological signs of chorioamnionitis and half of the group did not show such signs. A statistical, significant increase in IL-1ra, Il-6 and IL-8 values from early to late pregnancy was seen in the Swedish pregnant women. Among the Mozambican women, no statistically significant increase in the above-mentioned interleukins was observed when comparing women with and without histological signs of chorioamnionitis. Term Swedish and Mozambican women did not show differences in cytokine levels. There were no detectable values of IL-1 beta in either Swedish or Mozambican women. IL-1ra, IL-6 and IL-8 increased in amniotic fluid from the second to the third trimester in the Swedish cohort. No correlation was found between histological chorioamnionitis and elevated cytokine levels of amniotic fluid in term pregnant women not in labour. An equally good cytokine response was found among Swedish and Mozambican third-trimester non-labouring women.
Amniocentesis↗
The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines.
PU.1 is a hematopoietic transcription factor belonging to the Ets-family. It is identical to the Spi-1 oncogene, which is implicated in spleen focus-forming virus-induced murine erythroleukemias. PU.1 seems to be required for early development of multiple hematopoietic lineages, but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage-differentiation lineage. It binds the so-called Pu box, an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages. We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation, from early precursors to differentiated plasma cells. PU.1 mRNA expression and PU.1 DNA binding activity, as measured by Northern blot analysis and electrophoretic mobility shift assay, respectively, were evident in cell lines representing pro-B, pre-B, and mature B cells. We could also show Pu box-dependent transactivation of a reporter gene in transient transfections in these cell lines. In contrast, in a number of multiple myeloma cell lines, representing differentiated, plasma cell-like B cells, PU.1 DNA binding activity, mRNA expression, and Pu box-dependent transactivation were absent or detectable at a very low level. In lymphoblastoid cell lines, which exemplify an intermediate stage of B-cell differentiation, a reduced expression and activity were observed. The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines. At present, it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells.
B-Lymphocytes↗