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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Gene expression profiling of leukemic cell lines reveals conserved molecular signatures among subtypes with specific genetic aberrations.

Hematologic malignancies are characterized by fusion genes of biological/clinical importance. Immortalized cell lines with such aberrations are today widely used to model different aspects of leukemogenesis. Using cDNA microarrays, we determined the gene expression profiles of 40 cell lines as well as of primary leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1], t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14)[IGH@/MYC], t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11)[PICALM/MLLT10], t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed that hematopoietic cell lines of diverse origin, but with the same primary genetic changes, segregated together, suggesting that pathogenetically important regulatory networks remain conserved despite numerous passages. Moreover, primary leukemias cosegregated with cell lines carrying identical genetic rearrangements, further supporting that critical regulatory pathways remain intact in hematopoietic cell lines. Transcriptional signatures correlating with clinical subtypes/primary genetic changes were identified and annotated based on their biological/molecular properties and chromosomal localization. Furthermore, the expression profile of tyrosine kinase-encoding genes was investigated, identifying several differentially expressed members, segregating with primary genetic changes, which may be targeted with tyrosine kinase inhibitors. The identified conserved signatures are likely to reflect regulatory networks of importance for the transforming abilities of the primary genetic changes and offer important pathogenetic insights as well as a number of targets for future rational drug design.

Acute Disease↗
PubMed2004

First-principles theory of intermediate-valence f-electron systems.

We propose a first-principles based method for calculating the electronic structure and total energy of solids in an intermediate-valence configuration. The method takes into account correlation effects (d-f Coulomb interaction) and many-body renormalization of the effective hybridization parameter of the f system. As an example, the formation of a pressure-induced intermediate-valence state in Yb is considered and its electronic structure and equation of state are calculated and compared to experimental data. The agreement is found to be excellent for both properties, and we argue that the developed method, which applies to any element or compound, provides for the first time a quantitative theoretical treatment of intermediate-valence materials.

Journal Article↗
PubMed2004

Auger energy shifts in fcc AgPd random alloys from complete screening picture and experiment.

We extend the complete screening picture to ab initio calculations of Auger kinetic energy and Auger parameter shifts in metallic alloys. Experimental measurements of the L(3)M(4,5)M(4,5) Auger transition in fcc AgPd random alloys are compared with first-principles calculations and the results are in excellent agreement for both the Ag and Pd Auger shifts over the whole concentration range. We discuss the Auger kinetic energy shifts in terms of single-hole states for the 2p(3/2) core level and double-hole states for the 3d(5/2) level.

Journal Article↗
PubMed2004

High-pressure melting of molybdenum.

The melting curve of the body-centered cubic (bcc) phase of Mo has been determined for a wide pressure range using both direct ab initio molecular dynamics simulations of melting as well as a phenomenological theory of melting. These two methods show very good agreement. The simulations are based on density functional theory within the generalized gradient approximation. Our calculated equation of state of bcc Mo is in excellent agreement with experimental data. However, our melting curve is substantially higher than the one determined in diamond anvil cell experiments up to a pressure of 100 GPa. An explanation is suggested for this discrepancy.

Journal Article↗
PubMed2004

Fluctuating lattice constants of indium under high pressure.

Recent high-pressure investigations of elemental In have yielded controversial results. We show that the observed high-pressure face-centered orthorhombic (fco) structure can be explained as an intermediate state between two body-centered tetragonal (bct) structures with different c/a ratios (c/a < square root [2] and c/a > square root [2], respectively). In a pressure range from about 50 to 200 GPa these two bct structures correspond to local minima of the total energy with respect to orthorhombic distortion of the ground-state bct In structure. The fco saddle point represents a tiny barrier and even at low temperatures rapid structural fluctuations should occur. Such a situation has not been identified in any other elemental metal.

Journal Article↗
PubMed2004

Cognitive test performance in relation to psychotic symptoms and paranoid ideation in non-demented 85-year-olds.

BACKGROUND: Clinical studies suggest that psychotic and paranoid states in late life are associated with cognitive dysfunction. However, it is not clear whether this finding would be observed in general population samples of non-demented elderly, particularly after adjustment for potential confounding factors. METHOD: A representative sample of non-demented 85-year-olds living in the community or in institutions in Göteborg, Sweden (N = 347) was examined using a psychiatric and physical examination (including a medical history), key-informant interview, psychometric testing and review of medical records. Individuals with psychotic symptoms and paranoid ideation were compared with the mentally healthy regarding tests of verbal ability, inductive logical reasoning, spatial ability, perceptual speed, basic arithmetic, primary memory and secondary memory. RESULTS: Non-demented 85-year-olds with psychotic symptoms or paranoid ideation performed specifically worse on tests measuring verbal ability, logical reasoning and two tests of spatial ability after adjustment for sex, education, hearing impairment, visual deficits, somatic disorders, depression, 3-year-mortality rate and incident dementia. CONCLUSIONS: Psychotic symptoms and paranoid ideation were associated with lower performance on cognitive tests related to verbal ability, logical reasoning and spatial ability in non-demented 85-year-olds after adjustment for potential confounders.

Aged↗
PubMed2004

Gender differences in heritability of depressive symptoms in the elderly.

BACKGROUND: The present study aimed to investigate the relative importance of genetic and environmental influences on depressive symptoms in the elderly. METHOD: Depressive symptoms were assessed through the Center for Epidemiological Studies-Depression (CES-D) scale. The CES-D scale was administered to 959 twin pairs (123 female MZs, 90 male MZs, 207 same-sex female DZs, 109 same-sex male DZs and 430 opposite-sex DZs) aged 50 years or older (mean age 72 years). A dichotomous depressed state variable was constructed based on CES-D cut-offs and self-reported use of antidepressant medication. Structural equation models were fitted to the data to dissect genetic and environmental variance components. RESULTS: The sex-specific heritability estimates for depressive symptoms were 14% for males and 29% for females and 23% when constrained to be equal for men and women. The prevalence of clinically significant depressive symptoms was 16% for men and 24% for women. Heritability estimates for the dichotomous depressed state measure were 7% for males and 49% for females in the full model and 33% when constrained to be equal. CONCLUSION: Our results suggest that depressive symptoms in the elderly are moderately heritable, with a higher heritability for women than men, although differences in heritability estimates were not statistically significant.

Aged↗
PubMed2004

Autologous del(20q)-positive erythroid progenitor cells, re-emerging after DLI treatment of an MDS patient relapsing after allo-SCT, can provide a normal peripheral red blood cell count.

A 54-year-old RhD-negative male with del(20q)-positive myelodysplastic syndrome was transplanted with bone marrow from an HLA-identical RhD-positive sibling donor. Cytogenetic relapse was detected 21 months after stem cell transplantation (SCT), with reappearance of the original del(20q)-positive clone and reversion to recipient RhD-negative blood group. The patient received sequential donor lymphocyte infusions (DLIs), resulting in mild graft-versus-host disease and pure red cell aplasia. At 2 years post DLI, the patient remains in a stable condition, despite a dominance of recipient-derived erythro- and granulopoiesis originating in del(20q)-carrying progenitor cells. We conclude that reappearance of autologous erythropoiesis, upon relapse after allogeneic SCT, may be predictive of erythropenia after DLI and that re-emerging autologous del(20q)-positive erythropoiesis post DLI can provide a normal peripheral red blood cell count. Furthermore, in patients relapsing after blood-group-mismatched transplantation, a possible reversion to recipient blood group should be considered prior to blood transfusion or DLI.

Chromosome Deletion↗
PubMed2004

Adenosine A receptors are necessary for protection of the murine heart by remote, delayed adaptation to ischaemia.

AIMS: Adenosine is involved in classic pre-conditioning (PC) in most species, acting through especially adenosine A1 and A3 receptors. We studied whether the adenosine A1 receptor (A1R) was important for remote, delayed adaptation to ischaemia using a mouse with targeted deletion of the A1R gene. METHODS: Remote, delayed adaptation was evoked by brain ischaemia (BIPC) through bilateral ligation of the internal carotid arteries. Through microdialysis probes placed in the brain and the abdominal aorta, we found that plasma adenosine increased following carotid artery ligation. Twenty-four hours after ligation, hearts were isolated, Langendorff perfused and subjected to 40 min global ischaemia and 60 min reperfusion. Hearts from sham operated and BIPC animals either with (A1R+/+) or without (A1R-/-) the gene for the adenosine A(1)R were compared with each other. RESULTS: In wild types, BIPC reduced infarct size and improved functional recovery during reperfusion, but BIPC did not protect hearts of A1R-/- mice. There were no significant differences between sham-operated A1R+/+ and A1R-/- in recovery of function or infarct size. The mitogen-activated protein kinases (MAPKs) extracellular signal-regulated protein kinase1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) were phosphorylated during reperfusion of sham treated hearts. The increase in ERK1/2 and p38 phosphorylation detected was attenuated in hearts of BIPC or A1R-/- animals. CONCLUSION: During BIPC adenosine acting on the A1R appears necessary for myocardial protection. MAPK signalling may possibly be involved in organ protection during the delayed phase of remote, delayed adaptation.

Adaptation, Physiological↗
PubMed2003

Association between depressed mood in the elderly and a 5-HTR2A gene variant.

The aim of this study was to investigate any possible association between depressed mood in the elderly and two candidate SNPs in the serotonin system: one in the 5-HTR2A gene promotor (-1438 G/A) and one in the 5-HT transporter gene (-925 C/A). DNA from a population-based Swedish twin sample (N = 1,592; mean age = 73) was genotyped using Pryosequencing trade mark. An association was found between the 5-HTR2A gene promotor polymorphism and depressed mood (OR: 1.5, CI: 1.1-2.1) for the A/A genotype in the total sample. When the sample was analyzed by gender, a significant association (OR: 2.4, CI: 1.4-4.4) was found for males and the A/A genotype, but not for females. The 5-HT transporter gene was not associated with depressed mood in this elderly population. These results suggest that there might be different genetic mechanisms for males and females contributing to the development of depressed mood in the elderly.

Aged↗
PubMed2003

Iron-silica interaction at extreme conditions and the electrically conducting layer at the base of Earth's mantle.

The boundary between the Earth's metallic core and its silicate mantle is characterized by strong lateral heterogeneity and sharp changes in density, seismic wave velocities, electrical conductivity and chemical composition. To investigate the composition and properties of the lowermost mantle, an understanding of the chemical reactions that take place between liquid iron and the complex Mg-Fe-Si-Al-oxides of the Earth's lower mantle is first required. Here we present a study of the interaction between iron and silica (SiO2) in electrically and laser-heated diamond anvil cells. In a multianvil apparatus at pressures up to 140 GPa and temperatures over 3,800 K we simulate conditions down to the core-mantle boundary. At high temperature and pressures below 40 GPa, iron and silica react to form iron oxide and an iron-silicon alloy, with up to 5 wt% silicon. At pressures of 85-140 GPa, however, iron and SiO2 do not react and iron-silicon alloys dissociate into almost pure iron and a CsCl-structured (B2) FeSi compound. Our experiments suggest that a metallic silicon-rich B2 phase, produced at the core-mantle boundary (owing to reactions between iron and silicate), could accumulate at the boundary between the mantle and core and explain the anomalously high electrical conductivity of this region.

Journal Article↗
PubMed2003

Metal-nonmetal transition in the boron group elements.

Structural competition in boron group elements has been studied by means of ab initio calculations. For boron we predict a structural change alpha-B-->alpha-Ga accompanied by a nonmetal-metal transition at a pressure of about 74 GPa. For Al and Ga we find an icosahedron based elemental modification (alpha-B) 0.22 and 0.05 eV/atom, respectively, higher in energy than the corresponding metallic ground state structures. In particular, the low energy difference for Ga raises expectations into the experimental feasibility of new modifications for these elements, especially in nanosized systems.

Journal Article↗
PubMed2003

Antisite-defect-induced surface segregation in ordered NiPt alloy.

By means of first principles simulations we demonstrate that tiny deviations from stoichiometry in the bulk composition of the NiPt-L1(0) ordered alloy have a great impact on the atomic configuration of the (111) surface. We predict that at T=600 K the (111) surface of the Ni51Pt49 and Ni50Pt50 alloys corresponds to the (111) truncation of the bulk L1(0) ordered structure. However, the (111) surface of the nickel deficient Ni49Pt51 alloy is strongly enriched by Pt and should exhibit the pattern of the 2x2 structure. Such a drastic change in the segregation behavior is due to the presence of different antisite defects in the Ni- and Pt-rich alloys and is a manifestation of the so-called off-stoichiometric effect.

Journal Article↗
PubMed2003

Plasma cytokine profiles in elderly humans.

It is known that as we age, immune dysregulation often occurs, leading to failing health, and increased susceptibility to a number of different diseases. In this study we have investigated plasma cytokine profiles in order to identify immune markers of ageing. Plasma samples were obtained from 138 participants of the Swedish longitudinal NONA study (aged 86, 90 and 94 years) and 18 healthy Swedish volunteers (aged between 32 and 59 years). Our results show significantly increased levels of the pro-inflammatory cytokine interleukin-6 (P<0.0001) and soluble intercellular adhesion molecule-1 (P<0.0001) in the elderly group. The anti-inflammatory cytokine interleukin-10 did not alter with age whereas active (naturally processed) transforming growth factor-beta levels were significantly (P<0.0001) increased in the elderly group. No difference was observed between males and females. These data suggest that there are measurable changes in cytokine profiles with ageing with increased levels of potentially harmful molecules, which may contribute to immune alterations and declining health in the elderly population.

Adult↗
PubMed2003

Biochemical values in persons older than 82 years of age: report from a population-based study of twins.

According to international standards, reference values for biochemical tests should be obtained in disease-free subjects and for therapies that may influence measurement values. For elderly persons, especially the very old, such a requirement is difficult to meet, since few of these individuals are free of ongoing or former diseases. The present study of a population-based Swedish twin sample comprises 535 individuals (186 males, 349 females) who were at least 82 years of age at blood sampling. Survival over a 6-year period is used as a reference of overall health. Baseline test values for subjects surviving 6 years are compared with results for persons who died in the follow-up period. Results, including mean and median values, standard deviations and ranges, were given for both genders in the total sample. Cases outside the 5th and 95th percentiles were then excluded, as were those who died during the follow-up period. In a third step, cases with disorders and therapies known to influence measurement values were also excluded. The risk of dying during the observation period was calculated across measurements from the lowest and highest 10th and 20th percentiles. The specific impact of proximity to death on the biochemical values, in addition to age effects, was analysed by comparing co-twins discordant for survival over 7 years. Increased mortality was indicated for subjects of both genders with high serum levels of urea, urate, gamma-GT, free thyroxin and plasma homocysteine. In females, low serum values for albumin and total cholesterol were associated with increased mortality. A lower cholesterol level was found 4 years before death, while a lower HDL-cholesterol level was associated with an increased risk of death across the entire 7-year period.

Aged↗
PubMed2003

Association of biochemical values with morbidity in the elderly: a population-based Swedish study of persons aged 82 or more years.

BACKGROUND: Various inter-dependent factors influence serum biochemical values. In the elderly, the impact of these factors may differ compared with younger age groups and therefore population-based studies among older people are needed. The specific morbidity in old age, including also various types of drug therapy, should be observed. METHODS: Various biochemical tests in 349 females and 186 males over 81 years of age were carried out and the associations of biochemical values with morbidity, drug therapy, anthropometry and gender were estimated. RESULTS: Biochemical serum values deviate in various diseases, characterized by increased frequency in the elderly, i.e. congestive heart failure, osteoporosis, hip fractures, depression and dementia. All of these diseases present a tendency to increased homocysteine, usually combined with low folate. Cases with intact cognitive function throughout the six years after sampling are characterized by low homocysteine, which is the opposite of what is found in dementia. Furthermore, congestive heart failure is associated with impaired creatinine clearance and increased urea and urate, and osteoporosis and hip fractures are characterized by low albumin and cholesterol. Increased values for urate and impaired creatinine clearance are found in coronary diseases. In gout, multiple biochemical changes take place. For cases with a history of diabetes, arterial hypertension, peptic ulcer and malignancy, few changes are found compared with the values of the total sample. Furosemide therapy is associated with the same pattern as congestive heart failure, and laxative treatment is characterized by low folate and high homocysteine values.

Aged↗
PubMed2003

Mild cognitive impairment in the oldest old: a comparison of two approaches.

The main purpose of the current investigation was to examine the predictive utility of two sets of criteria for mild cognitive impairment (MCI). A second purpose was to determine the incidence of MCI in a longitudinal, population-based sample of the oldest old in Sweden. The participants were from the larger 'Origins of Variance in the Old-Old: Octogenarian Twins' (OCTO-Twin) study, identified through the Swedish Twin Registry. Participants were initially aged 80 or above with a mean age of 83 and were re-examined after two, three, six and eight years. The sample for this study consisted of 263 elders that were randomly selected singletons from twin pairs. Mild cognitive impairment was rated at baseline using both Petersen'sand Ritchie's criteria. Petersen's criteria emphasize memory and memory complaint whereas Ritchie's criteria use a broader set of cognitive indicators. The incidence rate was comparable to that of other studies, however, neither set of criteria predicted subsequent dementia. The failure to confirm subsequent dementia suggests that there may be many sources of MCI in very late life besides incipient dementia. The presence of a key informant, as well as the weighting of performance across domains by an experienced clinician, both of which are hard to quantify, may be the key elements that give predictive values to MCI in prior studies.

Activities of Daily Living↗