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Biomedical subjects

J Larsson

Publications and source records attributed to J Larsson.

At least 19 recordsLinked to original sources

Professional artist, good Samaritan, servant and co-ordinator: four ways of understanding the anaesthetist's work.

BACKGROUND: Evaluating clinical competence among anaesthetists has so far focused mostly on theoretical knowledge and practical skills. According to theory, however, the way anaesthetists understand their own work has also greatly influenced the development of professional competence. The aim of this study was to investigate how anaesthetists understand their work. METHODS: Nineteen Swedish anaesthetists were interviewed. The interviews were open and sought answers to three questions 1) When do you feel you have been successful in your work?; 2) What is difficult or what hinders you in your work?; and 3) What is the core of your professional anaesthesia work? Phenomenographic analysis was performed. RESULTS: Four ways of understanding the anesthesiologists' professional work were found: 1) Give anaesthesia and control the patient's vital functions; 2) Help the patient, alleviate his/her pain and anxiety; 3) Give service to the whole hospital to facilitate the work of other doctors and nurses, caring for severely ill patients; and 4) Organize and direct the operation ward to make the operations list run smoothly. CONCLUSIONS: This study shows that anaesthetists understand their work in qualitatively different ways, which can be assumed to affect their work actions and also the way their competence develops. This has implications for the education of anaesthetists; it is important to find ways of making anaesthetists in training consciously aware of the different ways their work can be understood, as this will give them better prerequisites for future competence development.

Adult↗

Influence of factor V Leiden on the development of neovascularisation secondary to central retinal vein occlusion.

AIMS: To investigate if the presence of factor V Leiden has an influence on the prognosis in central retinal vein occlusion (CRVO). METHODS: 166 patients with CRVO were studied retrospectively. They were tested for factor V Leiden using DNA analysis. The presence of the mutation was studied in correlation with the development of neovascular complications 1 year after the thrombotic event. RESULTS: 56 of 166 patients (34%) developed neovascular complications after 1 year. In the patients who had the studied mutation 11 of 20 (55%) had developed neovascular complications after 1 year, compared to 45 of 146 patients (31%) in the group without factor V Leiden (p=0.04). CONCLUSION: The presence of factor V Leiden seems to enhance the risk of developing neovascular complications in CRVO.

Activated Protein C Resistance↗

Obstructive jaundice results in increased liver expression of uncoupling protein 2 and intact skeletal muscle glucose metabolism in the rat.

BACKGROUND: A majority of patients with pancreatic cancer have obstructive jaundice and diabetes with skeletal muscle insulin resistance. Surgery for these patients is associated with significant morbidity. Uncoupling protein 2 (UCP2) has been proposed to regulate energy expenditure and promote liver vulnerability. The effects of obstructive jaundice on muscle glucose metabolism and expression of UCP2 in liver and muscle are unknown. METHODS: Rats were operated with bile duct ligation (BDL). After 7 days, UCP2 mRNA levels were determined in liver and muscle. Simultaneously, insulin-stimulated glucose transport and glycogen synthesis in skeletal muscle were analyzed in vitro. RESULTS: The jaundiced rats lost more weight than pair-fed controls. UCP2 mRNA levels were increased 5-fold in liver but not in muscle in jaundiced rats compared to pair-fed controls. The jaundiced rats were hypoglycemic and hypoinsulinemic but demonstrated intact or enhanced insulin action on skeletal muscle glucose transport and glycogen synthesis in vitro. Muscle glycogen content was increased in the jaundiced rats. CONCLUSIONS: Experimental obstructive jaundice in the rat is associated with increased liver expression of UCP2, rapid weight loss, and intact insulin action on skeletal muscle glucose metabolism. Obstructive jaundice, by upregulated liver UCP2, may contribute to the cachexia and high surgical morbidity observed in these patients, but not to skeletal muscle insulin resistance in pancreatic cancer patients.

Animals↗

The BTB/POZ domain of the regulatory proteins Bric à brac 1 (BAB1) and Bric à brac 2 (BAB2) interacts with the novel Drosophila TAF(II) factor BIP2/dTAF(II)155.

The BTB/POZ domain is an evolutionarily conserved protein-protein interaction domain present in the N-terminal region of numerous transcription factors involved in development, chromatin remodeling, and human cancers. This domain is involved in homomeric and heteromeric associations with other BTB/POZ domains. The Drosophila BTB/POZ proteins Bric à brac 1 (BAB1) and Bric à brac 2 (BAB2) are developmentally regulated transcription factors which are involved in pattern formation along the proximo-distal axis of the leg and antenna, in the morphogenesis of the adult ovaries, and in the control of sexually dimorphic characters. We have identified partners of the BAB1 protein by using the two-hybrid system. The characterization of one of these proteins, called BIP2 for BAB Interacting Protein 2, is presented. BIP2 is a novel Drosophila TATA-box Protein Associated Factor (TAF(II)), also named dTAF(II)155. We show that the BTB/POZ domains of BAB1 and BAB2 are sufficient to mediate a direct interaction with BIP2/dTAF(II)155. This provides a direct link between these BTB/POZ transcription factors and the basal transcriptional machinery. We discuss the implications of the interaction between a BTB/POZ domain and a TAF(II) for the molecular mechanisms of transcriptional control mediated by BTB/POZ transcription factors.

Animals↗

Painting of fourth, a chromosome-specific protein in Drosophila.

Chromosome-specific gene regulation is known thus far only as a mechanism to equalize the transcriptional activity of the single male X chromosome with that of the two female X chromosomes. In Drosophila melanogaster, a complex including the five Male-Specific Lethal (MSL) proteins, "paints" the male X chromosome, mediating its hypertranscription. Here, with the molecular cloning of Painting of fourth (Pof), we describe a previously uncharacterized gene encoding a chromosome-specific protein in Drosophila. Unlike the MSL proteins, POF paints an autosome, the fourth chromosome of Drosophila melanogaster. Chromosome translocation analysis shows that the binding depends on an initiation site in the proximal region of chromosome 4 and spreads in cis to involve the entire chromosome. The spreading depends on sequences or structures specific to chromosome 4 and cannot extend to parts of other chromosomes translocated to the fourth. Spreading can also occur in trans to a paired homologue that lacks the initiation region. In the related species Drosophila busckii, POF paints the entire X chromosome exclusively in males, suggesting relationships between the fourth chromosome and the X and between POF complexes and dosage-compensation complexes.

Amino Acid Sequence↗

Pancreatic cancer cells require an EGF receptor-mediated autocrine pathway for proliferation in serum-free conditions.

In-vitro and in-vivo studies have shown that autocrine growth factors and receptors are frequently expressed in human malignancies. Few of these studies, however, provide evidence that the identified autocrine pathway is functional. In this study, a functional autocrine growth pathway in pancreatic cancer has been identified using an in-vitro cell culture system. When pancreatic cancer cells were grown without change of medium, proliferation was greater than when either medium was replaced frequently (HPAF, CAPAN-2, PANC-1 or SW1990) or cells were grown in the presence of the EGF receptor tyrosine kinase inhibitor AG1478 or the MEK inhibitor PD098059 (HPAF or CAPAN-2). Activity of extracellular-regulated kinases (ERK) 1 and 2 and c- jun and c- fos mRNA levels were significantly elevated in CAPAN-2 cells cultured continuously in serum-free medium. Collectively, the observations indicate that the EGF receptor and the ERK MAP kinase pathway mediate autocrine signals. In contrast to previous reports, the GRP and IGF-I receptors were shown not to be required for autocrine effects on pancreatic cancer cell proliferation. Autocrine stimulation of the EGF receptor can contribute to sustained mitogenic activity and proliferation of pancreatic cancer cells.

Cell Division↗

Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice.

Deletion of the transforming growth factor beta1 (TGF-beta1) gene in mice has previously suggested that it regulates both hematopoiesis and angiogenesis. To define the function of TGF-beta more precisely, we inactivated the TGF-beta type I receptor (TbetaRI) gene by gene targeting. Mice lacking TbetaRI die at midgestation, exhibiting severe defects in vascular development of the yolk sac and placenta, and an absence of circulating red blood cells. However, despite obvious anemia in the TbetaRI(-/-) yolk sacs, clonogenic assays on yolk sac-derived hematopoietic precursors in vitro revealed that TbetaRI(-/-) mice exhibit normal hematopoietic potential compared with wild-type and heterozygous siblings. Endothelial cells derived from TbetaRI-deficient embryos show enhanced cell proliferation, improper migratory behavior and impaired fibronectin production in vitro, defects that are associated with the vascular defects seen in vivo. We thus demonstrate here that, while TbetaRI is crucial for the function of TGF-beta during vascular development and can not be compensated for by the activin receptor-like kinase-1 (ALK-1), functional hematopoiesis and development of hematopoietic progenitors is not dependent on TGF-beta signaling via TbetaRI.

Activin Receptors, Type I↗

Probing impulsive strain propagation with X-ray pulses.

Pump-probe time-resolved x-ray diffraction of allowed and nearly forbidden reflections in InSb is used to follow the propagation of a coherent acoustic pulse generated by ultrafast laser excitation. The surface and bulk components of the strain could be simultaneously measured due to the large x-ray penetration depth. Comparison of the experimental data with dynamical diffraction simulations suggests that the conventional model for impulsively generated strain underestimates the partitioning of energy into coherent modes.

Journal Article↗

[Clostridium difficile-associated diarrhea--a growing problem in geriatric care].

From 1994 to 1998 the incidence of Clostridium difficile-associated diarrhoea (CDAD) in the Department of Geriatric Medicine, Huddinge University Hospital increased from 0.5% to 2.2% of all admissions. Corresponding figures for the whole hospital were 0.3% and 0.6%, respectively. The increase in CDAD at the Department of Geriatric Medicine was parallel with a more than doubled consumption of antibiotics. All geriatric patients with CDAD had been treated with antibiotics before onset of diarrhoea. Out of the antibiotic prescriptions 48% were a cephalosporin (mainly cefuroxim). In a matched reference group of geriatric patients 51% had been treated with antibiotics during the hospital stay. The patients with CDAD spent 27 +/- 14 days in hospital as compared to 13 +/- 9 days (P < 0.05) in the reference population.

Aged↗

Distribution of iodine 125-labeled alpha1-microglobulin in rats after intravenous injection.

The 28-kd plasma protein alpha(1)-microglobulin is found in the blood of mammals and fish in a free, monomeric form and as high-molecular-weight complexes with molecular masses above 200 kd. In this study, iodine 125-labeled free and high-molecular weight rat alpha(1)-microglobulin (a mixture of alpha(1)-microglobulin/alpha(1)-inhibitor-3 and alpha(1)-microglobulin/fibronectin complexes) were injected intravenously into rats. The distribution of the proteins was measured by using scintillation camera imaging. Both forms of (125)I-labeled alpha(1)-microglobulin were rapidly cleared from the blood, with a half-life of 2 and 16 minutes for the initial and late phase, respectively, for free alpha(1)-microglobulin; and a half-life of 3 and 130 minutes for the initial and late phase, respectively, for the complexes. After 45 minutes, 6%, 16%, 27%, 13%, and 34% of the free (125)I-labeled alpha(1)-microglobulin and 18%, 21%, 6%, 10%, and 42% of the (125)I-labeled alpha(1)-microglobulin complexes were found in the blood, gastrointestinal tract, kidneys, liver, and the remainder of the body, respectively. The local distribution of injected (125)I-labeled alpha(1)-microglobulin in intestines and kidneys was investigated by microscopy and autoradiography. In the intestine, both forms were distributed in the basal layers, villi, and luminal contents. The results also suggested intracellular labeling of epithelial cells. Well-defined local regions containing higher concentrations of injected protein could be seen in the intestine. In the kidneys, both forms were found mostly in the cortex. Free (125)I-labeled alpha(1)-microglobulin was found predominantly in epithelial cells of a subset of the tubules, whereas the (125)I-labeled complexes were more evenly distributed. Intracellular labeling was indicated for both alpha(1)-microglobulin forms. The results thus indicate a rapid transport of (125)I-labeled alpha(1)-microglobulin from the blood to most tissues.

Animals↗

Receptors and ligands for autocrine growth pathways are up-regulated when pancreatic cancer cells are adapted to serum-free culture.

Overexpression of autocrine growth factors and their receptors has been reported in many human cancers. The study of autocrine-regulated pathways using in vitro culture systems can be hindered by the presence of fetal bovine serum in culture medium. A human pancreatic cancer cell line (HPAF) was slowly weaned from its dependence on fetal bovine serum and subsequently maintained in serum-free conditions. Growth factor secretion studies showed that production of autocrine growth factors such as transforming growth factor alpha, gastrin-releasing peptide, and insulin-like growth factor I from weaned cells increased three times compared with nonweaned cells (p < 0.01). The epidermal growth factor and gastrin-releasing peptide receptor densities were also increased in weaned cells (2 times and 2.5 times, respectively, p < 0.05). The proliferation of weaned cells cultured continuously in the same medium was significantly greater than of nonweaned cells (p < 0.05). Collectively, these data indicate that weaned pancreatic cancer cells can proliferate in the absence of serum by up-regulating autocrine pathways.

Binding, Competitive↗

Photopic 30 Hz flicker ERG as a predictor for rubeosis in central retinal vein occlusion.

AIMS: To investigate the predictive value of the cone b-wave implicit time in the photopic compared with the scotopic 30 Hz flicker ERG for rubeosis in central retinal vein occlusion. METHODS: 44 patients with a central retinal vein occlusion were examined with full field electroretinogram (ERG). RESULTS: The average implicit time in the photopic 30 Hz flicker ERG in patients who developed rubeosis (n=15) was 38.3 ms. In the patients who did not develop rubeosis (n=29) it was 31.3. The difference is statistically significant (p=0.0000000004). CONCLUSION: The photopic cone b-wave implicit time in the 30 Hz flicker ERG is a good predictor for rubeosis.

Adult↗

Su(z)12, a novel Drosophila Polycomb group gene that is conserved in vertebrates and plants.

In both Drosophila and vertebrates, spatially restricted expression of HOX genes is controlled by the Polycomb group (PcG) repressors. Here we characterize a novel Drosophila PcG gene, Suppressor of zeste 12 (Su(z)12). Su(z)12 mutants exhibit very strong homeotic transformations and Su(z)12 function is required throughout development to maintain the repressed state of HOX genes. Unlike most other PcG mutations, Su(z)12 mutations are strong suppressors of position-effect variegation (PEV), suggesting that Su(z)12 also functions in heterochromatin-mediated repression. Furthermore, Su(z)12 function is required for germ cell development. The Su(z)12 protein is highly conserved in vertebrates and is related to the Arabidopsis proteins EMF2, FIS2 and VRN2. Notably, EMF2 is a repressor of floral homeotic genes. These results suggest that at least some of the regulatory machinery that controls homeotic gene expression is conserved between animals and plants.

Amino Acid Sequence↗

A 4D approach to the analysis of functional brain images: application to FMRI data.

This paper presents a new approach to functional magnetic resonance imaging (FMRI) data analysis. The main difference lies in the view of what comprises an observation. Here we treat the data from one scanning session (comprising t volumes, say) as one observation. This is contrary to the conventional way of looking at the data where each session is treated as t different observations. Thus instead of viewing the v voxels comprising the 3D volume of the brain as the variables, we suggest the usage of the vt hypervoxels comprising the 4D volume of the brain-over-session as the variables. A linear model is fitted to the 4D volumes originating from different sessions. Parameter estimation and hypothesis testing in this model can be performed with standard techniques. The hypothesis testing generates 4D statistical images (SIs) to which any relevant test statistic can be applied. In this paper we describe two test statistics, one voxel based and one cluster based, that can be used to test a range of hypotheses. There are several benefits in treating the data from each session as one observation, two of which are: (i) the temporal characteristics of the signal can be investigated without an explicit model for the blood oxygenation level dependent (BOLD) contrast response function, and (ii) the observations (sessions) can be assumed to be independent and hence inference on the 4D SI can be made by nonparametric or Monte Carlo methods. The suggested 4D approach is applied to FMRI data and is shown to accurately detect the expected signal.

Brain Chemistry↗

Obesity increases the severity of acute experimental pancreatitis in the rat.

BACKGROUND: Studies in patients with acute pancreatitis have shown a correlation between obesity and serious complications or a fatal outcome. However, the mechanisms by which obesity aggravates acute pancreatitis are not known. In the present study we used the sodium taurocholate model of pancreatitis to examine the effect of obesity on severity and outcome in acute experimental pancreatitis (AEP). METHODS: AEP was induced at two degrees of severity by retrograde infusion of sodium taurocholate (0.2 ml x 3% or 0.4 ml x 3.5%) into the pancreatic duct of rats with obesity induced by high-fat diet, genetically obese (GO) rats or lean control rats. Surviving animals were sacrificed 72 h after induction of pancreatitis. RESULTS: In the low-dose experiment, there were no significant differences in pancreatic histology or survival rate between the groups. In the high-dose experiment, the GO rats had a significantly lower 72-h survival rate than the high-fat obese (HFO) or lean control (LC) groups (GO 25% versus HFO 73%, P < 0.05; GO 25% versus LC 100%, P < 0.001). Survival rates in the high-dose experiment correlated strongly with basal liver fat content (R2 = 0.86). Pancreatic histology showed significantly more fat necrosis and a higher total pathological mean score in the HFO rats than in the LC animals (both P < 0.05). CONCLUSIONS: Obesity had a negative influence on the outcome of necrotizing pancreatitis that was related to the magnitude of the pancreatic insult. The sodium taurocholate model in obese rats would be useful for future mechanistic studies of the effect of obesity on pancreatitis.

Animals↗

Effects of long-term infusion of anorexic concentrations of islet amyloid polypeptide on neurotransmitters and neuropeptides in rat brain.

Islet amyloid polypeptide (IAPP or amylin) potently reduces food intake in rats at or near physiological concentrations. Although the mechanisms of action of IAPP are not understood, the brain is a suggested site. Changes in hypothalamic and striatal neurotransmission have been reported following acute systemic administration of a pharmacological concentration of IAPP. In the current study, we evaluated the effects of chronic administration of low doses of IAPP on satiety-related neurotransmitters and neuropeptides in the hypothalamus, hippocampus, striatum, left cortex, and right cortex of the rat. Doses of 0, 5 and 25 pmol IAPP/kg-min were administered subcutaneously for 2 or 5 days. Food intake was reduced by 27 and 44% (both P<0.001) for the 5 and 25 pmol/kg-min groups, respectively, in the 2-day experiment and was decreased by 14% (P<0.01) and 24% (P<0.001), respectively, in the 5-day experiment. Body weight was significantly decreased in a dose-dependent fashion. In the 2-day experiment, norepinephrine increased in the hypothalamus in the 5 pmol IAPP/kg-min group, and neurotensin increased in the hippocampus in the 25 pmol/kg-min rats (both P<0.05). In the 5-day, 5 pmol/kg-min rats, 5-hydroxyindoleacetic acid (5-HIAA) increased in the hypothalmus and cholecystokinin (CCK) increased in the striatum (both P<0.05). In the 5-day, 25 pmol/kg-min group, neuropeptide Y (NPY) increased in the hypothalamus (P<0.01) and CCK increased in the hypothalmus and striatum (both P<0.05). The present study confirms that IAPP is a potent anorectic peptide at low doses and suggests that IAPP not only affects classical neurotransmitters in the brain but also alters concentrations of neuropeptides known to be involved in food intake.

3,4-Dihydroxyphenylacetic Acid↗

[Guidelines for management of patients with acute pancreatitis].

During recent years new concepts and methods have been introduced in the management of acute pancreatitis. Severity and risk of complications show wide variation. Outcome is also dependent on the physician's experience and on his local resources. In this light the Swedish Society of Upper Abdominal Surgery has elaborated national guidelines for management. Attention is paid to diagnosis, severity assessment and etiology. Furthermore, guidelines are offered for treatment of mild and severe pancreatitis, as well as for the management of pseudocysts. The role of multidisciplinary intensive care specialist teams in the management of severe disease is emphasized. The guidelines are supported by the Swedish Society of Gastroenterology, the Swedish Society of Gastroenterology, the Swedish Society of Anesthesiology and Intensive Care and by experts from other Nordic countries.

APACHE↗

Time-resolved X-Ray diffraction from coherent phonons during a laser-induced phase transition

Time-resolved x-ray diffraction with picosecond temporal resolution is used to observe scattering from impulsively generated coherent acoustic phonons in laser-excited InSb crystals. The observed frequencies and damping rates are in agreement with a model based on dynamical diffraction theory coupled to analytic solutions for the laser-induced strain profile. The results are consistent with a 12 ps thermal electron-acoustic phonon coupling time together with an instantaneous component from the deformation-potential interaction. Above a critical laser fluence, we show that the first step in the transition to a disordered state is the excitation of large amplitude, coherent atomic motion.

Journal Article↗