PubMed Health⌕ Search

Biomedical subjects

A Hansson

Publications and source records attributed to A Hansson.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Atrial fibrillation--new knowledge yields new therapeutic possibilities].

Atrial fibrillation (AF) is the most common cardiac arrhythmia prompting treatment. Advances in our knowledge of the pathophysiology of AF provide the basis for new and improved treatment modalities. Thus, focal excitation and localised impulse conduction defects are possible trigger factors which can be counteracted by focal ablation and pacing synchronisation, respectively. Perpetuation of AF, caused by continuous multisite re-entry, is promoted by successive shortening of repolarisation. Internal defibrillation and anatomical limitation of re-entry are treatments that counteract perpetuation of the arrhythmia. Current knowledge of AF and the application of new treatments are discussed by the Lund AF research group.

Atrial Fibrillation↗
PubMed1999

Manganese sulfate-dependent glycosylation of endogenous glycoproteins in human skeletal muscle is catalyzed by a nonglucose 6-P-dependent glycogen synthase and not glycogenin.

Glycogenin, a Mn2+-dependent, self-glucosylating protein, is considered to catalyze the initial glucosyl transfer steps in glycogen biogenesis. To study the physiologic significance of this enzyme, measurements of glycogenin mediated glucose transfer to endogenous trichloroacetic acid precipitable material (protein-bound glycogen, i.e., glycoproteins) in human skeletal muscle were attempted. Although glycogenin protein was detected in muscle extracts, activity was not, even after exercise that resulted in marked glycogen depletion. Instead, a MnSO4-dependent glucose transfer to glycoproteins, inhibited by glycogen and UDP-pyridoxal (which do not affect glycogenin), and unaffected by CDP (a potent inhibitor of glycogenin), was consistently detected. MnSO4-dependent activity increased in concert with glycogen synthase fractional activity after prolonged exercise, and the MnSO4-dependent enzyme stimulated glucosylation of glycoproteins with molecular masses lower than those glucosylated by glucose 6-P-dependent glycogen synthase. Addition of purified glucose 6-P-dependent glycogen synthase to the muscle extract did not affect MnSO4-dependent glucose transfer, whereas glycogen synthase antibody completely abolished MnSO4-dependent activity. It is concluded that: (1) MnSO4-dependent glucose transfer to glycoproteins is catalyzed by a nonglucose 6-P-dependent form of glycogen synthase; (2) MnSO4-dependent glycogen synthase has a greater affinity for low molecular mass glycoproteins and may thus play a more important role than glucose 6-P-dependent glycogen synthase in the initial stages of glycogen biogenesis; and (3) glycogenin is generally inactive in human muscle in vivo.

Acarbose↗
PubMed1999

Molecular basis for semidominance of missense mutations in the XANTHA-H (42-kDa) subunit of magnesium chelatase.

During biosynthesis of bacteriochlorophyll or chlorophyll, three protein subunits of 140, 70, and 42 kDa interact to insert Mg2+ into protoporphyrin IX. The semidominant Chlorina-125, -157, and -161 mutants in barley are deficient in this step and accumulate protoporphyrin IX after feeding on 5-aminolevulinate. Chlorina-125, -157, and -161 are allelic to the recessive xantha-h mutants and contain G559A, G806A, and C271T mutations, respectively. These mutations cause single amino acid substitutions in residues that are conserved in all known primary structures of the 42-kDa subunit. In vitro complementation and reconstitution of Mg-chelatase activity show that the 42-kDa subunits are defective in the semidominant Chlorina mutants. A mutated protein is maintained in the Chlorina plastids, unlike in the xantha-h plastids. Heterozygous Chlorina seedlings have 25-50% of the Mg-chelatase activity of wild-type seedlings. Codominant expression of active and inactive 42-kDa subunits in heterozygous Chlorina seedlings is likely to produce two types of heterodimers between the strongly interacting 42-kDa and 70-kDa subunits. Reduced Mg-chelatase activity is explained by the capacity of heterodimers consisting of mutated 42-kDa and wild-type 70-kDa protein to bind to the 140-kDa subunit. The 42-kDa subunit is similar to chaperones that refold denatured polypeptides with respect to its ATP-to-ADP exchange activity and its ability to generate ATPase activity with the 70-kDa subunit. We hypothesize that the association of the 42-kDa subunit with the 70-kDa subunit allows them to form a specific complex with the 140-kDa subunit and that this complex inserts Mg2+ into protoporphyrin IX.

Amino Acid Sequence↗
PubMed1998

Local renin-angiotensin system in the pineal gland.

Besides the classical endocrine renin-angiotensin system (RAS), a local RAS has been described also in the brain. We attempted to clarify the existence of a local RAS in the pineal gland. Through the use of a ribonuclease protection assay, it proved possible to detect the mRNA for angiotensinogen (AOGEN), for the angiotensin receptor type 1A (AT1a) and 1B (AT1b) and for the angiotensin-converting enzyme (ACE) in pineal glands from rats. Renin mRNA, however, could not be found by this method. By in situ hybridization and immunocytochemistry, AOGEN mRNA was co-localized with the astrocyte marker glial fibrillary acidic protein. AT1b mRNA expression exceeded the expression of AT1a mRNA and was co-localized with the pinealocyte-specific tryptophan hydroxylase. Thus, in the mammalian pineal gland there is a local formation of the components of the RAS. The presence of angiotensin II receptors further substantiates a role for angiotensins and the pineal RAS in the physiology of this gland.

Angiotensinogen↗
PubMed1998

Follow-up of patients with low back pain during pregnancy.

OBJECTIVE: To identify the long-term risk for low back pain among women with previous severe low back pain during pregnancy. METHODS: In a previous prospective study, 79 pregnant women developed low back pain severe enough to require sick leave. Twelve years later a questionnaire was sent to 62 of these women and 84 controls who did not develop severe low back pain during pregnancy. The questionnaire asked about occupation, low back pain in general and during later pregnancies, and sick leave due to low back pain. There were also questions regarding use of oral contraceptives and its possible relation to low back pain. RESULTS: The response rate was 84% in the back pain group and 80% among controls. The two groups were similar according to the percentage of women having had another pregnancy (33 of 52 [63%] versus 39 of 67 [58%]) but ten (19%) of the women with previous low back pain stated they had refrained from another pregnancy because of their fear of low back pain compared with only one control. Almost all women (31 of 33) with previous severe low back pain experienced the same symptoms in a subsequent pregnancy, compared with 17 of 39 (44%) controls. Even when they were not pregnant, women with previous low back pain suffered more often and used more sick leave due to low back pain (44 of 52 versus 43 of 67, chi2 = 5.68, P < .05). The location (sacroiliac joint or lumbar affection) of the previous low back pain did not affect the long-term prognosis. In a logistic regression model, previous low back pain during pregnancy was the only independent risk factor for low back pain during a subsequent pregnancy, whereas an occupation involving physical demand did not affect the results. However, together with previous low back pain during pregnancy, heavy occupation increased the risk for current nonpregnant low back pain. CONCLUSION: Women with severe low back pain during pregnancy have an extremely high risk for experiencing a new episode of severe low back pain during another pregnancy and when not pregnant.

Adult↗
PubMed1998

Fibroblasts derived from human chronic diabetic wounds have a decreased proliferation rate, which is recovered by the addition of heparin.

We have studied the growth kinetics of fibroblasts derived from uninjured skin and chronic wounds in non-diabetic and diabetic (IDDM) patients. DNA measurements during the first 24 h after cell starvation showed that fibroblasts derived from chronic wounds, both non-diabetic and diabetic, display a decreased adhesion and proliferation. When determining the rate of proliferation after another 48, 72 and 96 h, a significant decrease in the proliferation rate was found in the chronic wound fibroblasts compared to those from uninjured skin. Furthermore, we have investigated the effects of heparin, hyaluronic acid and other heparin-like substances on the proliferation of non-diabetic and diabetic fibroblasts. We found that these substances stimulated the proliferation of human fibroblasts derived from both normal skin and chronic wounds measured as DNA content. Stimulation with heparin normalized the proliferation of the diabetic chronic wound fibroblasts. This effect was independent of the presence of serum. The effect of heparin was dose-dependent and most pronounced during the first 24 h of stimulation. These results suggest that heparin may be of importance in the treatment of chronic diabetic wounds.

Anticoagulants↗
PubMed1998

Right atrial free wall conduction velocity and degree of anisotropy in patients with stable sinus rhythm studied during open heart surgery.

AIMS: Although the perpetuation of several supraventricular arrhythmias is critically dependent upon intra-atrial conduction, the literature lacks detailed information on normal values of conduction velocity and degree of anisotropy. In order to explore these factors further, we have measured conduction velocities at the right atrial free wall during sinus rhythm and during atrial pacing in four directions parallel and perpendicular to the atrioventricular groove in patients with normal atria and stable sinus rhythm. METHODS AND RESULTS: Using a Bard Cardiac Mapping System, atrial ECGs were recorded using a 3 x 4 cm electrode array with 56 equally spaced bipolar electrodes in 12 patients undergoing open heart surgery due to ischaemic heart disease or Wolf-Parkinson-White syndrome. A bipolar pen probe connected to a Medtronic 5328 stimulator was used for pacing at a 10% higher rate than sinus rhythm. The local activation times were manually set and isochronal activation maps were created for each recording. The conduction velocities were calculated from the activation maps over a distance ranging from 2.2 to 4.2 cm. The majority of the activation maps showed no signs of anisotropy; the others had less than 15% spatial inhomogeneity of conduction. Mean conduction velocity, calculated from five consecutive beats, was 88 +/- 9 cm.s-1 (mean +/- SD), ranging between 68 +/- 4 and 103 +/- 3 cm.s-1 during sinus rhythm. Mean conduction velocity during atrial pacing was 81 +/- 16 cm.s-1 at a propagation direction of 0 degree, 74 +/- 14 cm.s-1 at a 90 degrees direction, 79 +/- 12 cm.s-1 at 180 degrees and 78 +/- 20 cm.s-1 at 270 degrees, where 0 degree was parallel to the atrioventricular groove in the cranial direction and the angle increased counter-clockwise. Mean conduction velocity during sinus rhythm was significantly higher (P < 0.05) than during atrial pacing at the 90 degrees and 180 degrees directions but not compared to atrial pacing at 0 degree or 270 degrees. There was no significant difference in mean conduction velocity in different directions during atrial pacing. CONCLUSION: Although anisotropy was documented during conduction velocity in individual cases, conduction velocity was not dependent on propagation direction at the epicardial right atrial free wall in patients with stable sinus rhythm. These findings do not exclude the presence of internodal preferential pathways as these are located sub-epicardially and a marked transmural discordance in activation has previously been documented in the vicinity of such pathways.

Adult↗
PubMed1998

Insulin-like growth factor-I-induced DNA synthesis in insulin-secreting cell line RINm5F is associated with phosphorylation of the insulin-like growth factor-I receptor and the insulin receptor substrate-2.

A proliferative effect of insulin-like growth factor-I (IGF-I) was previously shown in pancreatic islets. However, the mechanism under which IGF-I actions are exerted in insulin-secreting cells is not clear. The rat insulinoma cell line, RINm5F, was shown to have both IGF-I receptors and IGF-Il/mannose-6-phosphate receptors. IGF-I binding to cell surface receptors stimulated phosphorylation of 97 kDa and 93 kDa subunits of the IGF-I receptor and incorporation of [3H]thymidine into RINm5F cells. Both the IGF-I-induced protein phosphorylation and [3H]thymidine incorporation were abolished in the presence of the tyrosine kinase inhibitor, genistein. Under basal conditions, IGF-I did not induce insulin release or changes in cytosolic free Ca2+ concentration. Immunoprecipitation of proteins from RINm5F cells, using phosphotyrosine antibodies, followed by western blotting using antibody against IRS-1 revealed no distinct band of phosphorylated insulin receptor substrate (IRS)-1. Instead, tyrosine-phosphorylated IRS-2 was detected and stimulated by IGF-I when western blotting was performed using antibody against IRS-2. These results indicate that IRS-1 is not likely to be involved in IGF-I signalling in RINm5F cells. Hence, IGF-I stimulated DNA synthesis in RINm5F cells was associated with phosphorylation of IGF-I receptors and IRS-2.

Animals↗
PubMed1998

Cortical and medullary hemodynamics in deoxycorticosterone acetate-salt hypertensive mice.

The effect of acutely increasing renal perfusion pressure or extracellular fluid volume on renal medullary and cortical blood flow was examined in the low-renin deoxycorticosterone acetate (DOCA)-salt hypertension model in mice. A 50-mg DOCA tablet was implanted, and 1% saline was given as drinking water for 3 wk. Medullary and cortical blood flow were determined with laser-Doppler flowmetry, and whole-kidney blood flow was measured with a transit-time ultrasound flowprobe around the renal artery. In control mice, total renal blood flow ranged from 6.3 and 7.6 ml/min per g kidney weight and in DOCA-salt mice from 4.3 and 4.7 ml/min per g kidney weight, respectively, and was minimally affected as renal perfusion pressure was increased. Renal vascular resistance increased correspondingly. During stepwise increases in renal artery pressure from 90 to 140 mmHg, medullary blood flow progressively increased in control mice to 125% of baseline values, whereas cortical blood flow did not change. In DOCA-salt mice, increasing BP from 100 to 154 mmHg had no effect on either cortical or medullary blood flow. Urine flow and sodium excretion were lower in DOCA-salt mice than in controls and increased nearly to the same extent in both groups after volume expansion with isotonic saline. Total renal blood flow increased after saline loading, more in controls than in DOCA-salt mice. Increases in medullary blood flow after saline loading were up to 122% of baseline values in controls and demonstrated a significantly steeper slope than the 110% of baseline increases in DOCA-salt mice. Cortical blood flow, however, was not different between the groups. Thus, medullary blood flow is not as tightly autoregulated as cortical blood flow in normal mice. Natriuresis with acute volume loading is facilitated by increased medullary blood flow. In DOCA-salt mice, the medullary blood flow reaction to renal perfusion pressure increases is abolished, whereas flow increases with extracellular volume expansion are diminished. These results suggest that diminished pressure-natriuresis responses in DOCA-salt mice are related to perturbed medullary blood flow.

Angiotensinogen↗
PubMed1997

BIACORE analysis of histidine-tagged proteins using a chelating NTA sensor chip.

While BIACORE instruments are routinely used for kinetic measurements and for the determination of binding constants, the immobilization of a ligand onto the sensor chip surface has to be individually optimized for every system. We show here that the histidine (His) tag, routinely used in protein purification and in detection is an ideal tag for immobilization, despite the intrinsically low affinity between an immobilized metal ion and the His tag. This is due to strong rebinding effects caused by the high surface density of immobilized Ni2+-nitrilotriacetic acid (NTA) on the chips used here. The immobilization of the ligand can be adjusted to a low level using the same chip, such that mass transport limitation and rebinding of the analyte to the immobilized ligand is minimal. Nine different proteins with different numbers of His tags were tested for stable binding to the Ni2+-NTA surface. Most proteins with one His tag dissociate very rapidly from the Ni2+-NTA surface, and the KD for the interaction between His tag and Ni2+-NTA was estimated to about 10(-6) m at neutral pH. In contrast, two His tags are usually found to be sufficient for stable binding. The kinetics of the chaperonin system of Escherichia coli GroEL and GroES were analyzed as a model using this system and found to be very similar to those obtained with covalently immobilized ligands. The sensor chip can be reused many times, because of the powerful regeneration methods. The ligand can be freshly immobilized after each cycle, thus eliminating potential denaturation upon regeneration as a source of error.

Adenosine Triphosphate↗
PubMed1997

Rat insulinoma-derived pancreatic beta-cells express a functional leptin receptor that mediates a proliferative response.

In addition to its interaction at hypothalamic sites to affect feeding and energy expenditure, leptin has been shown to exhibit a proliferative response in erythropoietic cells. The functional leptin receptor is also present in pancreatic islets and we now demonstrate that a commonly used clonal insulin secreting beta-cell line, RINm5F, expresses high levels of the Ob-Rb mRNA. Leptin causes an increase in tyrosine phosphorylation of a number of intracellular proteins and a dose related (10 nM-200 nM) increase in expression of the immediate-early gene, c-fos. This precedes a leptin induced proliferative response in serum-deprived RINm5F cells, which suggests that leptin might be involved in the complex regulation of proliferation of the pancreatic beta-cell.

Animals↗
PubMed1997

High glucose-induced growth factor resistance in human fibroblasts can be reversed by antioxidants and protein kinase C-inhibitors.

We have studied the influence of high glucose on basal fibroblast proliferation, growth factor induced cellular proliferation and the effects of antioxidants, protein kinase C-inhibitors and troglitazone. Fibroblast cultures were obtained from five patients undergoing mammary reduction plastic surgery. A fluorometric method was used for determining total DNA in the cell samples, DNA content being proportional to cell number. D-Glucose at 15.5 mM and above was shown to inhibit fibroblast proliferation, and the cells were resistant to growth factors such as IGF-I and EGF at this glucose concentration. H7, bisindolylmaleimide IX, troglitazone, alpha-tocopherol acetate, Q10, ascorbic acid, beta-carotene, DMTU and selenite were all found to reverse the high glucose-induced growth factor resistance observed in human fibroblasts. We believe that these findings may be of value in the understanding and future treatment of wound healing in diabetic foot ulcers.

Antioxidants↗
PubMed1997

Nitric oxide synthase and renin-angiotensin system gene expression in salt-sensitive and salt-resistant Sabra rats.

The molecular mechanisms of salt sensitivity and the contribution of the kidney to salt-induced hypertension in Sabra rats are imperfectly defined. We investigated the expression of the nitric oxide (NO) system (endothelial, inducible, and neural NO synthases) and renin-angiotensin system (renin, angiotensinogen, and angiotensin II type 1A receptor) gene components in the kidneys of SBN/y (salt-resistant) and SBH/y (salt-sensitive) Sabra rat substrains, with and without deoxycorticosterone acetate (DOCA)-salt treatment. We also looked for immunocytochemical evidence of angiotensin II, the effector peptide of the renin-angiotensin system. Inducible and neural NO synthase gene expression values were lower in SBH/y than in SBN/y before and after DOCA-salt treatment. The gene expression level of endothelial NO synthase was not different in SBH/y and SBN/y, either with or without DOCA salt. Renin gene expression was significantly higher in kidneys of SBN/y than in kidneys of SBH/y rats, whereas angiotensinogen gene expression was significantly lower in SBN/y. After DOCA-salt treatment, renin gene expression was strongly suppressed in both strains but more so in SBH/y. Angiotensinogen gene expression, on the other hand, was increased by DOCA salt in SBN/y rats so that the two strains were no longer different. Angiotensin II immunoreactivity was significantly higher in SBN/y than in SBH/y; however, after DOCA salt, immunoreactivity in both strains was no longer detectable. Angiotensin II type 1A receptor gene expression was not different between the two strains, either before or after DOCA-salt administration. We conclude that DOCA salt induced a decrease in the activity of the renin-angiotensin system but did not change NO synthase gene expression in SBH/y and SBN/y. Inducible and neural NO synthase gene expression values were less in SBH/y than in SBN/y, independent of DOCA-salt administration. Thus, the NO system could explain, at least in part, the salt resistance of SBN/y.

Angiotensin II↗
PubMed1996

Extracellular zinc ions induces mitogen-activated protein kinase activity and protein tyrosine phosphorylation in bombesin-sensitive Swiss 3T3 fibroblasts.

The growth factor-like effect of zinc in vitro and in vivo, which has long been recognized was investigated with respect to its mechanisms of action. Addition of zinc chloride to bombesin-sensitive Swiss 3T3 mouse fibroblasts induced a fourfold stimulation in the cytosolic myelin basic protein kinase activity. The response was dose- and time-dependent, with an ED50 of around 100 microM and a peak at 5 min. The kinase activity coeluted with p42 MAP kinase using chromatography on Mono-Q ion exchange. Intracellular loading of cells with the heavy metal chelator BTC-5N did not attenuate the response to zinc. The action of zinc was not suppressed by long-term pretreatment with 4-beta-phorbol dibutyrate (48 h). Addition of 0.3 mM vanadate alone did not increase the kinase activity, but prolonged the action of zinc when added simultaneously. Addition of zinc (0.3 mM) or epidermal growth factor for 1 min resulted in a marked increase in tyrosine phosphorylation of proteins with apparent molecular weights of approximately 100, 105-120, 215, and 240 kDa in whole cell extracts. Immunoprecipitation against the p85 subunit of phosphatidylinositol 3-kinase resulted in the appearance of two phosphotyrosine-containing proteins, 100 and 115 kDa, in extracts from cells treated with zinc or epidermal growth factor, indicating that the tyrosine phosphorylation was recognized by the corresponding SH2-domains. The present study demonstrates that extracellular zinc has the potential to partially mimic the action of growth factors on intracellular MAP kinase activation and protein tyrosine phosphorylation.

3T3 Cells↗
PubMed1996

Long-term treatment of Swiss 3T3 fibroblasts with dexamethasone attenuates MAP kinase activation induced by insulin-like growth factor-I (IGF-I).

Bone formation is reduced in hyperglucocorticoid states, e.g. Cushing's syndrome or long-term treatment with synthetic glucocorticoids during rheumatic diseases. possibly related to decreased sensitivity of the target to insulin-like growth factor-I (IGF-I). In this study, we have sought to identify postreceptor-mechanisms for glucocorticoid-induced resistance to insulin-like peptides in a model system. Treatment of Swiss 3T3 fibroblasts with 100 nM dexamethasone for 48h reduced IGF-I-induced activation of mitogen-activated protein kinase (MAP kinase). The level of insulin receptor substrate-1 (IRS-1) was reduced in dexamethasone-treated cells, as measured by Western blot; however, the pattern of tyrosine-phosphorylated protein subsequent to stimulation with IGF-I (1 min) was not altered. No inhibitory effect of dexamethasone was observed on the level of phosphotyrosine in IRS-1 in extracts from IGF-I-treated cells. The amount of IGF-I-induced association of insulin receptor substrate-1 and phosphatidylinositol 3-kinase was increased in steroid treated cells. Addition of IGF-I increased the synthesis of lipid, glycogen and protein, and the reduction of a tetrazolium dye, MTS, in untreated cells. The response to IGF-I in terms of glycogen synthesis was blunted, whereas the effect of IGF-I was unaffected for the other three parameters in cells pretreated with dexamethasone. These findings indicate that the activation of MAP kinase may be dissociated from IGF-I-induced anabolic pathways and tyrosine phosphorylation of IRS-1. The results agree with the previously proposed role for the activation of MAP kinase in the regulation of glycogen synthesis. Furthermore, they suggest that dexamethasone-induced reduction of IRS-1 expression may be important for the impaired activation of MAP kinase by insulin-like peptides in steroid-treated cells.

3T3 Cells↗
PubMed1996

Axial wall convergence of full veneer crown preparations. Documented for dental students and general practitioners.

The convergence angle in 478 full crown preparations was assessed. Of these preparations, 351 had been performed by general practitioners and 127 by dental students. Groups of preparations performed on incisors, premolars, and molars were compared, as were preparations performed by dentists and students. Two different convergence angles were measured for each tooth, buccolingually and mesiodistally. The results showed a mean angle of 21 degrees. The mean values for premolars and molars differed significantly. When a comparison was made of preparations performed by students, a significant difference was found between premolars and molars. The same comparison for general practitioners showed a significant difference both for incisors compared with molars and for premolars compared with molars. A wide range was found for the convergence of the axial walls, especially for the preparations performed by general practitioners.

Clinical Competence↗
PubMed1995

Occurrence of pleural plaques in workers with exposure to mineral wool.

The objective of this study was to investigate whether occurrence of pleural plaques is associated with exposure to mineral wool. The occurrence of pleural plaques on routine chest radiographs of 933 persons employed in the mineral wool manufacturing industry and 865 referents was compared. Twelve men from the mineral wool industry had pleural plaques, as against three of the referents (P > 0.05). The occurrence of pleural plaques among men in the mineral wool industry was not associated with an increased exposure to mineral wool or with length of time between start of employment and time of chest radiograph. The results do not support the notion that inhalation of man-made mineral fibers causes pleural plaques. It must, however, be conceded--keeping in mind the limits imposed by the study size--that nor do they provide grounds for refutation of such a hypothesis.

Adolescent↗