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Biomedical subjects

A Hansen

Publications and source records attributed to A Hansen.

At least 55 records · Page 3Linked to original sources
PubMed2001

Prognostic value of Doppler echocardiographic mitral inflow patterns: implications for risk stratification in patients with chronic congestive heart failure.

OBJECTIVES: This prospective study tested whether transmitral flow patterns add incremental value to peak oxygen consumption (VO2) in determining the prognosis of patients with chronic congestive heart failure (CHF) and systolic dysfunction. BACKGROUND: Peak VO2 is an objective marker of functional capacity and is routinely used as a criterion to identify heart transplant candidates. Diastolic dysfunction limits functional capacity, but its prognostic importance relative to that of peak VO2 is unknown. METHODS: Peak VO2 and mitral inflow velocities were prospectively measured in 311 consecutive patients (mean age 54 years, 84% male) with impaired left ventricular function (ejection fraction <40%; 88 patients with ischemic and 223 with dilated cardiomyopathy) who were evaluated for heart transplant candidacy. RESULTS: During a mean follow-up period of 512 +/- 314 days, 65 patients died and 43 patients underwent heart transplantation. Diastolic filling patterns, peak VO2 and left ventricular end-diastolic diameters were independent predictors of cardiac mortality. In patients with peak VO2 < or = 14 ml/min per kg body weight, the outcome was markedly poorer in the presence of restrictive filling patterns as compared with their absence (two-year survival rate 52% vs. 80%). Similarly, despite peak VO2 levels >14 ml/min per kg, the outcome was less favorable in the presence of restrictive filling patterns (two-year survival rate 80% vs. 94%). A risk-stratification model based on the identified independent noninvasive predictors separated groups into those with high (93%), intermediate (65%) and low (39%) two-year survival rates. CONCLUSIONS: Transmitral flow patterns add incremental value to peak VO2 in determining the prognosis of patients with CHF and impaired systolic function.

Blood Flow Velocity↗
PubMed2001

Immunoglobulin Vkappa light chain gene analysis in patients with Sjögren's syndrome.

OBJECTIVE: Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltration of the salivary glands with a previously reported predominance of Vkappa-bearing B cells and produce a variety of autoantibodies, indicating that there is a humoral autoimmune component in this syndrome. This study was undertaken to determine whether there are primary deviations of immunoglobulin V gene usage, differences in somatic hypermutation, defects of selection, or indications for perturbances of B cell maturation in SS. METHODS: Individual peripheral B cells from patients with SS were analyzed for their Ig V gene usage, and the findings were compared with results in normal controls. RESULTS: Molecular differences, as reflected by findings in the nonproductive Vkappa repertoire of the patients, were identified by an enhanced usage of Jkappa2 gene segments and a lack of mutational targeting toward RGYW/WRCY sequences compared with controls. A greater usage of Vkappa1 family members and a reduced frequency of Vkappa3 gene segments in the productive repertoire suggested differences in selection, possibly driven by antigen. Overall positive selection for mutations, especially for replacements in the complementarity-determining region and for mutations in RGYW/WRCY, similar to that found in controls, was detected. CONCLUSION: Disturbances of strictly regulated B cell maturation, during early B cell development as indicated by prominent Jkappa2 gene usage and during germinal center reactions as indicated by a lack of targeting of the hypermutation mechanism, might contribute to the emergence of autoimmunity in SS.

Adult↗
PubMed2001

Immunoglobulin Vlambda light chain gene usage in patients with Sjögren's syndrome.

OBJECTIVE: To determine whether patients with Sjögren's syndrome (SS) have abnormalities in Ig Vlambda and Jlambda gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation. METHODS: Individual peripheral B cells from SS patients were analyzed for their Vlambda gene usage by single-cell polymerase chain reaction amplification of genomic DNA and compared with those from normal controls. RESULTS: Molecular differences from controls in Vlambda-Jlambda recombination were identified that were reflected by findings in the nonproductive Vlambda repertoire of the patients, including enhanced rearrangement of Vlambda10A and Jlambda2/3 gene segments. In addition, a number of abnormalities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 Vlambda genes (2A2, 2B2, 2C, and 7A), representing 56% of all productive Vlambda rearrangements, was observed, suggesting positive selection of these genes. Overutilization of Jlambda2/3 and underutilization of Jlambda7 in both nonproductive and productive Vlambda rearrangements of SS patients compared with controls suggested decreased receptor editing in SS. The mutational frequency did not differ from that in controls, and positive selection of mutations into the productive V gene repertoire was found, similar to that in controls, although mutational targeting toward RGYW/WRCY motifs, typically found in controls, was not found in SS patients. CONCLUSION: Disturbed regulation of B cell maturation with abnormal selection, defects in editing Ig receptors, and abnormal mutational targeting may contribute to the emergence of autoimmunity in SS.

Aged↗
PubMed2001

Is the "candy-wrapper" effect of (32)P radioactive beta-emitting stents due to remodeling or neointimal hyperplasia? Insights from intravascular ultrasound.

A recognized limitation of radioactive stents is the development of restenosis at the stent edges, known as the "candy-wrapper" effect. The mechanisms of this effect remain incompletely understood and controversial. The aim of this study is to assess the effect of endovascular irradiation on neointima formation and vascular remodeling. (32)P Palmaz-Schatz stents (1.5-4 microCi) were implanted in 11 patients with restenosis after previous percutaneous transluminal coronary angioplasty (PTCA). Intravascular ultrasound (IVUS) images of target sites and adjunct vessel segments were acquired both during intervention and after 6 months. The angiographic restenosis rate was 54%, and the MLD decreased from 2.21 +/- 0.6 mm to 1.38 +/- 0.4 mm at follow-up (P < 0.01). IVUS analysis demonstrated that late lumen loss was the result of neointimal tissue proliferation, which was nonuniformly distributed and exaggerated at both the central articulation and the distal stent edges. Negative remodeling did not contribute to restenosis. In contrast, we found a linear relationship between increase of area stenosis and a positive remodeling index (r = 0.84, P < 0.0001). Restenosis after implantation of (32)P Palmaz-Schatz stents was mainly the result of neointimal tissue proliferation which tended to be nonuniformly distributed in the stent articulation and edges. Negative remodeling or stent recoil was not observed. Cathet Cardiovasc Intervent 2001;54:41-48.

Aged↗
PubMed2001

Features of mono- and multinucleated bone resorbing cells of the zebrafish Danio rerio and their contribution to skeletal development, remodeling, and growth.

To provide basic data about bone resorbing cells in the skeleton during the life cycle of Danio rerio, larvae, juveniles, and adults (divided into six age groups) were studied by histological procedures and by demonstration of the osteoclast marker enzyme tartrate-resistant acid phosphatase (TRAP). Special attention was paid to the lower jaw, which is a standard element for fish bone studies. The presence of osteoclasts at endosteal surfaces of growing bones of all animals older than 20 days reveals that resorption is an important part of zebrafish skeletal development. The first bone-resorbing cells to form are mononucleated. They appear in 20-day-old animals concurrently in the craniofacial skeleton and vertebral column. Mononucleated osteoclasts are predominant in juveniles. Regional differences characterize the appearance of osteoclasts; at thin skeletal elements (neural arches, nasal) mononucleated osteoclasts are predominant even in adults. Multinucleated bone-resorbing cells were first observed in 40-day-old animals and are the predominant osteoclast type of adults. Both mono- and multinucleated osteoclasts contribute to allometric bone growth but multinucleated osteoclasts are also involved in lacunar bone resorption and repeated bone remodeling. Resorption of the dentary follows the pattern described above (mononucleated osteoclasts precede multinucleated cells) and includes the partial removal of Meckel's cartilage. Bone marrow spaces created by resorption are usually filled with adipose tissue. In conclusion, bone resorption is primarily subjected to the demands of growth, the appearance of mono- and multinucleated osteoclasts is site- and age-related, and bone remodeling occurs. The results are discussed in relation to findings in other teleosts and in mammals.

Animals↗
PubMed2001

Differential value of adenosine myocardial contrast echocardiography and dobutamine stress echocardiography in evaluating functional significance of coronary artery stenosis in a porcine model.

AIM: Myocardial contrast echocardiography (MCE) during adenosine induced hyperemia is an experimental method that detects flow limiting coronary artery stenosis by visualizing myocardial perfusion defects. Noninvasive detection of flow limiting coronary artery stenosis in clinical routine is a frequent domaine of dobutamine stress echocardiography (DSE) visualizing ischemia related regional wall motion abnormalities. This study investigated the values of adenosine MCE and DSE in the detection of functionally significant coronary artery stenosis in an experimental open chest pig model. METHODS: A total of 28 proximal LAD stenoses were instrumented in 12 animals. Reduction of coronary blood flow reserve (delta CFR [%] ) was calculated as a marker of functional significance of coronary artery stenosis (mild to moderate stenosis: delta CFR < or = 50%; severe stenosis: delta CFR > 50%). Fractional area shortening (FAS) and wall thickening (WT) were calculated to evaluate regional wall motion. Peak myocardial contrast intensities (PCI) were measured following aortic root injections of Levovist' to detect mocardial perfusion defects. RESULTS: As a group, severe stenosis significantly reduced wall motion response to dobutamine (delta FAS: 12.0 +/- 3.0%, vs. 20 +/- 3.0% without stenosis, p < 0.05; delta WT: 2.2 +/- 0.9 mm vs. 0.0 +/- 0.8 mm without stenosis, p < 0.05) and diminished myocardial opacification during hyperemia (PCI: 59 +/- 8 units vs. 143 +/- 16 units without stenosis, p < 0.05). Mild to moderate stenosis did not influence wall motion but reduced myocardial opacification (PCI 89 +/- 14 units vs. 143 +/- 16 units). PCI correlated more closely with alterations in CFR (r = -0.7, p < 0.0001) than did FAS (r = -0.5, p < 0.002) or WT (r = -0.2, p = 0.3). CONCLUSION: Adenosine myocardial contrast echocardiography detects flow limiting coronary artery stenosis and compares favorably to regional wall motion analysis during dobutamine infusion.

Adenosine↗
PubMed2001

Heat capacity of protein folding.

We construct a Hamiltonian for a single domain protein where the contact enthalpy and the chain entropy decrease linearly with the number of native contacts. The hydration effect upon protein unfolding is included by modeling water as ideal dipoles that are ordered around the unfolded surfaces, where the influence of these surfaces, covered with an "ice-like" shell of water, is represented by an effective field that directs the water dipoles. An intermolecular pair interaction between water molecules is also introduced. The heat capacity of the model exhibits, the common feature of small globular proteins, two peaks corresponding to cold and warm unfolding, respectively. By introducing ad hoc vibrational modes, we obtain quantitatively good accordance with experiments on myoglobin.

Models, Chemical↗
PubMed2001

Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins.

Dietary antioxidants that protect low-density lipoprotein (LDL) from oxidation may help to prevent atherosclerosis and coronary heart disease. The antioxidant activities of purified monomeric and dimeric hydroxycinnamates and of phenolic extracts from rye (whole grain, bran, and flour) were investigated using an in vitro copper-catalyzed human LDL oxidation assay. The most abundant ferulic acid dehydrodimer (diFA) found in rye, 8-O-4-diFA, was a slightly better antioxidant than ferulic acid and p-coumaric acid. The antioxidant activity of the 8-5-diFA was comparable to that of ferulic acid, but neither 5-5-diFA nor 8-5-benzofuran-diFA inhibited LDL oxidation when added at 10-40 microM. The antioxidant activity of the monomeric hydroxycinnamates decreased in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid. The antioxidant activity of rye extracts was significantly correlated with their total content of monomeric and dimeric hydroxycinnamates, and the rye bran extract was the most potent. The data suggest that especially rye bran provides a source of dietary phenolic antioxidants that may have potential health effects.

Antioxidants↗
PubMed2001

Echocardiographic quantification of left ventricular asynergy in coronary artery disease with Fourier phase imaging.

BACKGROUND: Visual evaluation of wall motion is subjective and may be difficult in patients with impaired left ventricular function. Current algorithms used to analyze wall motion usually neglect motion asynchrony that may be profoundly altered in coronary artery disease. This study was to investigate whether the extent of left ventricular asynergy can be used to quantify the severity of regional myocardial dysfunction by the use of Fourier phase imaging. METHODS: Echocardiographic cine loops of 21 patients with ischemic cardiomyopathy (EF < or = 40%) were mathematically transformed using a first-harmonic Fourier algorithm displaying the sequence of wall motion as phase angles in parametric images and regional phase histograms. Segmental fractional area shortening (FAC) and qualitative assessment of regional wall motion based on visual inspection served as reference method. RESULTS: There was an inverse linear relationship between FAC and phase angles (r = -0.75, p < 0.01). Normal endocardial motion yielded low phase angles (mean 16 +/- 15 degrees SD). With an increase in wall motion abnormalities, phase angles were progressively delayed by 56 +/- 38 degrees in hypokinetic, by 88 +/- 38 degrees in akinetic, and by 143 +/- 33 degrees (p < 0.001) in dyskinetic segments. CONCLUSIONS: These results demonstrate that left ventricular asynchrony is an indicator of regional myocardial dysfunction in coronary artery disease. Echocardiographic Fourier phase imaging can be used to quantify wall motion displaying contraction sequence in a simple and objective format.

Aged↗
PubMed2001

Demineralized Bone Matrix-stimulated Bone Regeneration in Rats Enhanced by an Angiogenic Dipeptide Derivate.

A lysyl-proline derivate (LP) known to stimulate angiogenesis and formation of granulation tissue was tested as a local additive to allogeneic demineralized bone matrix (DBM) using a rat craniotomy model. Peracetic-acid sterilized DBM (10 mg/defect) was implanted into three groups of 45 animals each with 0, 6 and 20 microg LP. Subsequent evaluation was done by descriptive histology, histomorphometry, and determination of the calcium content of the explants 7, 14, 28, 42 and 84 days post-implantation. Grafting with DBM alone resulted in defect bridging by newly formed bone with incorporated DBM residues on day 84. Addition of LP to the implants caused an enhanced capillarization on day 14 and 28 as well as an enhanced mineralization on day 14, 28, 42 and 84. Both effects were dose-dependent. These data suggest that the local application of a synthetic angiogenic factor significantly improve bone regeneration in DBM-grafted trephine defects in rats. Thereby, they reinforce the opinion that early angiogenesis is crucial for a number of subsequent events in the bone regeneration process.

Journal Article↗
PubMed2001

Comparison of the efficacy of virus inactivation methods in allogeneic avital bone tissue transplants.

Several procedures for inactivating viruses are used presently in the context of bone tissue transplants. Common methods used are gamma irradiation (25 kGy), treatment with moist heat (82.5 degrees C/15 min., lobator-sd2-system) as well as chemical sterilisation using peracetic acid-ethanol treatment (PES, 2% peracetic acid, 96% ethanol, Aqua [2:1:1], 200 mbar, agitation, 4 hours). Based on national and international guidelines, we tested the antivirucidal effectiveness of these methods in human bone transplants. Three enveloped viruses: human immunodeficiency virus type 2 (HIV-2), pseudorabies virus (PRV), bovine virus diarrhoea virus (BVDV), and three non-enveloped viruses were used: hepatitis A virus (HAV), poliovirus (PV-1), porcine/bovine parvovirus (PPV, BPV). Defatted spongiosa cuboids served as model in chemical treatment experiments, while cortical diaphyses were used in gamma irradiation experiments, and the effects of thermal treatment were tested in prepared femoral heads. The log(10) reduction was measured by cytopathogenic effects after virus titration (TCID(50)/mL). A dose of at least 33.9 kGy (bone model) at -30 +/- 5 degrees C was necessary to achieve a sufficient reduction (4 log(10) steps) of BPV, the most resistant one of all viruses investigated. Thermal treatment as well as PES treatment led to a reduction of virus titres by more than 4 log(10). Only HAV showed a reduction below 4 log(10) (2.87) with PES. After validation of the defatting step included for HAV-infected cells, a HAV-reduction of over 7 log(10) was found. All three sterilisation methods tested are recommended for bone transplant sterilisation, but only provided that additional safety measures (anamnestic informations, infectious serology, PCR in case of multiorgan donors) are taken.

Journal Article↗
PubMed2001

High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity.

WF10 is a stabilized chlorite matrix with immunosuppressive effects. In vitro studies have demonstrated its ability to suppress T cells and delay or abolish antigen presentation. Hence, WF10 may prove useful to prolong graft survival after transplantation. In this study, we evaluated the use of high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population, receiving high dose WF10 for 5 days, were compared with a matched control group. Ultrastructural examination of cardiac tissue as well as biochemical analysis of the cardiac enzymes troponin I, myoglobin and MB isoenzyme of creatine kinase showed no signs of damage. Thus, while prolonging graft survival, high dose WF10 seems to be non-cardiotoxic and as such should not contribute to the differential diagnosis of acute graft failure.

Animals↗
PubMed2001

The growth hormone-releasing hormone receptor: desensitisation following short-term agonist exposure.

We have investigated the effect of short-term preexposure of growth hormone-releasing hormone (GHRH) on the subsequent response to GHRH in a baby hamster kidney (BHK) cell line expressing the human GHRH receptor and in primary rat pituitary cells. In the BHK cells the receptor was rapidly desensitised in a homologous fashion. Preexposure with agents directly stimulating the cAMP pathway like forskolin and db-cAMP had no effect. In rat pituitary cells we also observed a rapid desensitisation of the GHRH response in an apparently homologous fashion. In both systems the desensitisation was dose-dependent with no change in the potency of the hormone in a subsequent stimulation, only the efficacy was decreased. In the rat pituitary cell, the response measured as growth hormone release was more sensitive to the agonist-induced desensitisation than the cAMP response. No indication of depletion of growth hormone (GH) stores was seen. In rat pituitary cells, contrary to observations in BHK cells, preexposure with both forskolin and db-cAMP desensitised a subsequent growth hormone-releasing hormone stimulation, indicating a heterologous desensitisation. Phorbol-12-myristate 13-acetate (PMA), on the other hand, had no effect. In the baby hamster kidney cells it was demonstrated that the GHRH receptor surface expression decreased following preexposure with GHRH. This phenomenon was observed only in whole cells suggesting a rapid internalisation process. Together, these data indicate that after short-term GHRH preexposure, both in a human and rat system, the following GHRH response is desensitised. In BHK cells this desensitisation is strictly homologous. In rat pituitary cells, on the other hand, the desensitisation is a mixed homologous/ heterologous type.

Adenylyl Cyclases↗
PubMed2001

Exploring the minimal substrate requirements for trans-cleavage by RNase P holoenzymes from Escherichia coli and Bacillus subtilis.

We analysed the processing of small bipartite model substrates by Escherichia coli and Bacillus subtilis RNase P and corresponding hybrid enzymes. We demonstrate specific trans-cleavage of a model substrate with a 4 bp stem and a 1 nucleotide (nt) 5' flank, representing to date the smallest mimic of a natural RNase P substrate that could be processed in trans at the canonical RNase P cleavage site. Processing efficiencies decreased up to 5000-fold when the 5' flank was shortened from 3 to 1 nt. Reduction of the 5' flank to 1 nt was more deleterious than reducing the stem from 7 to 4 bp, although the 4 bp duplex formed only transiently, in contrast to the stable 7 bp duplex. These results indicate that the crucial contribution of nt -2 in the single-stranded 5' flank to productive interaction is a general feature of A- and B-type bacterial RNase P enzymes. We also showed that an Rp-phosphorothioate modification at nt -2 interferes with processing. Bacterial RNase P holoenzymes are also capable of cleaving single-stranded RNA oligonucleotides as short as 5 nt, yielding RNase P-specific 5'-phosphate and 3'-OH termini, with measured turnover rates of up to 0.7 min-1. All cleavage sites were at least 2 nt away from the 5' and 3' ends of the oligonucleotides. Some cleavage site preferences were observed dependent on the identity of the RNase P RNA subunit.

Bacillus subtilis↗
PubMed2001

Effect of norethindrone acetate on hormone levels and markers of bone turnover in estrogen-treated postmenopausal women.

There is controversy concerning the effects of progestins on bone. Norethindrone acetate (NETA) is synthetic progesterone that also has estrogenic and androgenic effects. We tested its effects on hormone levels, lipids and biochemical markers of bone turnover in postmenopausal women who were on estrogen replacement therapy. Women were treated with NETA, 5 mg/d for 9 weeks. Estrogenic effects included a marked lowering of follicle stimulating hormone and luteinizing hormone. Androgenic effects included a decrease in sex hormone binding globulin and HDL cholesterol. Bone turnover showed inconsistent responses. Among markers of bone formation, bone specific alkaline phosphatase decreased significantly by 23% while procollagen peptides and osteocalcin showed a non-significant increase. The marker of bone resorption, N-telopeptide crosslinks of collagen, decreased by 19% at 6 weeks. These results indicate that NETA does not have a potent short-term anabolic effect on bone but does have effects that are likely to be mediated through the estrogen and androgen receptors.

Aged↗
PubMed2000

Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus.

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at high frequencies in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27(high) plasma cells and naive CD27(-) B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27(+) B cells coexpressing IgD were memory B cells preferentially using V(H)3 family members with multiple somatic mutations. CD27(high) plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V(H)4 family members. These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.

ADP-ribosyl Cyclase↗