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Biomedical subjects

A Hansen

Publications and source records attributed to A Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2004

Expression and localisation of matrix metalloproteinases and their natural inhibitors in fistulae of patients with Crohn's disease.

BACKGROUND: Fistulae are a troublesome complication of Crohn's disease but little is known of the final effector molecules responsible for matrix degradation. Although matrix metalloproteinases (MMPs) have been strongly implicated in tissue injury in Crohn's disease, their role in fistula formation is unknown. AIM: To determine the expression pattern of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in fistulae of patients with Crohn's disease. PATIENTS AND METHODS: Resected fistula specimens were obtained from patients with Crohn's disease (n = 11) and classified according to the predominant histological features-that is, acute versus chronic inflammation. Patients with fistulae due to other diseases (n = 9) and normal colon (n = 5) served as controls. MMP and TIMP protein expression was measured by single or double labelled immunohistochemistry, and mRNA expression by in situ hybridisation. MMP activity was measured by gelatin zymography. RESULTS: Compared with normal colon, strong MMP-3 expression was consistently observed in fistulae in Crohn's disease, irrespective of the stage of inflammatory activity. MMP-3 transcripts and protein were localised in large mononuclear cells and fibroblasts. MMP-9 transcripts and protein were expressed in granulocytes and only in fistulae with acute inflammation. Staining for MMP-1 and MMP-7 was weak and negative for MMP-10, whereas MMP-2 was equally expressed in normal colon and fistulae. TIMP-1, TIMP-2, and TIMP-3 expression was low in all samples. Similar expression patterns were found in fistulae of the disease control group. Fistulae also expressed active MMP-2 and MMP-9, as measured by gelatin zymography. CONCLUSION: MMP-3 and MMP-9 are markedly upregulated in intestinal fistulae and may contribute to fistula formation through degradation of the extracellular matrix, irrespective of the underlying disease process.

Adolescent↗
PubMed2003

Immune hemolysis-serological and clinical aspects.

The differential diagnosis of anemia must consider immune hemolytic anemias as a frequent cause. Whereas detection of anti-red blood cell (RBC) alloantibodies frequently induced by immunogenic stimuli (transfusion, pregnancy) is performed by routine serology, diagnosing autoimmune hemolytic anemias or drug-induced hemolytic anemias remains a challenge, usually requiring close collaboration of a number of disciplines. Positive direct antiglobulin test (Coombs' test) represents a central criterion in diagnosing immune hemolytic anemias, leading to further detailed analyses. The most-severe type of immune-mediated hemolysis is acute intravascular hemolysis after ABO incompatible RBC transfusion. This review highlights underlying biochemical aspects, immunohematological diagnostics, and the clinical relevance of RBC allo- and autoantibodies, including paroxysmal nocturnal hemoglobinemia and drug-induced hemolysis. Finally, current and partly experimental therapeutic strategies of immune hemolytic anemias are summarized.

ABO Blood-Group System↗
PubMed2003

Non-overt disseminated intravascular coagulation in patients during treatment with antithymocyte globulin for unrelated allogeneic hematopoietic stem cell transplantation.

We assessed the effect of rabbit antithymocyte globulin manufactured by Fresenius (ATG-F) on the hemostatic system in patients (n=12) with various hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT) from HLA-matched unrelated donors. For this purpose, we monitored different parameters of coagulation before, during and after the administration of ATG-F. As a control group, we recruited patients (n=10) undergoing HSCT from their HLA-identical siblings who did not receive ATG-F as part of their preparative regimens. At 24 and 48 h after ATG-F treatment had been initiated, we found a temporary rise in D-Dimer, tissue factor, soluble thrombomodulin and thrombin-antithrombin III complex levels and a significant decrease of platelet counts in patients treated with ATG-F as compared to the control group. No differences between the two groups could be detected with regard to global coagulation tests as well as the incidence of bleeding manifestations, thromboembolic complications or the development of vascular-occlusive-disease of the liver. This temporary state of a stressed but compensated coagulation system under ATG-F therapy can be addressed as nonovert disseminated intravascular coagulation (DIC). The effect was independent from the different conditioning regimens and eased off after cessation of ATG-F. We conclude that ATG-F can induce nonovert DIC in patients receiving antithymocyte globulin as part of their conditioning regimen for HSCT.

Adolescent↗
PubMed2003

Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjögren's syndrome.

Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using VH1-08 and VH2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the VH gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated VH rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive VH rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of JH6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using VH1-08) was also detected in the patient's peripheral repertoire.

Aged↗
PubMed2003

Effect of micronized progesterone on bone turnover in postmenopausal women on estrogen replacement therapy.

PURPOSE: To determine whether daily oral micronized progesterone affects bone turnover, as estimated by serum and urine biochemical markers, in postmenopausal women on long-term estrogen replacement therapy (ERT). METHODS: We recruited 14 women aged 65 or older to participate in a 9-week trial with micronized progesterone. Each woman had undergone a hysterectomy and was on unopposed ERT at time of study entry. Women received micronized progesterone 100 mg twice daily in the first week and then received 200 mg twice daily in weeks 2-9. We measured markers of bone turnover in serum and urine collected at baseline and at 3 weeks, 6 weeks, and 9 weeks on treatment. Markers of bone formation were serum bone alkaline phosphatase (BAP), N-terminal procollagen peptides (PINP), and osteocalcin (OC). Markers of bone resorption were urinary cross-linked N-terminal and C-terminal telopeptides of type I collagen. In addition, we measured serum progesterone, estradiol and sex hormone binding globulin, triglycerides, total cholesterol, and high-density lipoprotein (HDL)-cholesterol levels at baseline and at 9 weeks on treatment. RESULTS: Mean serum progesterone levels increased from 1.6 +/- 1.1 to 15.2 +/- 3.9 ng/mL, which was within the luteal phase range (3-25 ng/mL). Crosslinked C-telopeptides of type I collagen and osteocalcin increased significantly (p < 0.05) with progesterone treatment, however, other bone markers did not change. Estradiol, estrone, and SHBG levels did not change with treatment. High-density lipoprotein-cholesterol levels decreased 19% (p < 0.001) at 9 weeks on treatment compared to baseline but total and low-density lipoprotein (LDL) cholesterol and triglycerides did not change with treatment. CONCLUSION: In postmenopausal women on long-term estrogen replacement therapy, micronized progesterone (400 mg/d) increased one marker each of bone resorption and bone formation. Other sensitive markers of bone turnover did not change with treatment. Further, micronized progesterone decreased HDL-cholesterol in these women. Our data do not support a beneficial effect of micronized progesterone on bone or cardiovascular risk factors in postmenopausal women.

Aged↗
PubMed2002

[Pitfalls in hypertension management--misjudgements in diagnosis and therapy].

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman with arterial hypertension, diabetes type 2, peripheral vascular disease and Sjögren's syndrome presented with progressive weakness, dizziness, insomnia, palpitations and headache. These symptoms did not improve by changing her antihypertensive treatment. The patient's general condition was quite normal and there were no signs of acute or chronic cardiopulmonary decompensation. INVESTIGATIONS: Besides arterial hypertension, she also had an elevated body mass index, dyslipoproteinemia, microalbuminuria, diabetic metabolism, left ventricular hypertrophy with signs of an abnormal diastolic cardiac function as well as atherosclerotic lesions (in both carotid arteries) which were identified as the patient's cardiovascular risk factors. Ambulant blood pressure monitoring revealed decreasing BP values for a period of 5 hrs after drug intake but, subsequently, severe hypertensive values (up to 220 mmHg systolic) without adequate decrease at night. Moreover, a hyperkinetic regulation of her circulation was demonstrated by hemodynamic monitoring and assessment of the autonomic nervous system. TREATMENT: By changing drug treatment, i. e. administration of an anti-adrenergic calcium antagonist of the non-dihydropyridine type combined with an ACE inhibitor and a diuretic, respectively, (both given in fixed combinations) led to the normalization of the blood pressure and pulse rate as well as an improvement of the patient's condition. CONCLUSIONS: This case emphasizes the importance of ambulant blood pressure monitoring and an assessment of the heart rate in individually adapted antihypertensive drug therapy. The application of metabolically neutral fixed drug combinations with special regard to associated diseases, organ protection and the patient's compliance resulted in normotensive blood pressure values and an improvement of the quality of life.

Aged↗
PubMed2002

Dynamic rearrangements and packing regimes in randomly deposited two-dimensional granular beds.

We study the structural properties of two-dimensional granular packings prepared by random deposition from a source line. We consider a class of random ballistic deposition models based on single-particle relaxation rules controlled by a critical angle, and we show that these local rules can be formulated as rolling friction in the framework of dynamic methods for the simulation of granular materials. We find that a packing prepared by random deposition models is generically unstable, and undergoes dynamic rearrangements. As a result, the dynamic method leads systematically to a higher solid fraction than the geometrical model for the same critical angle. We characterize the structure of the packings generated by both methods in terms of solid fraction, contact connectivity, and anisotropy. Our analysis provides evidence for four packing regimes as a function of solid fraction, the mechanisms of packing growth being different in each regime.

Journal Article↗
PubMed2002

Myocardial contrast echocardiography yields best accuracy using quantitative analysis of digital data from pulse inversion technique: comparison with second harmonic imaging and harmonic power Doppler during simultaneous dipyridamole stress SPECT studies.

AIMS: This prospective study assesses the (1) feasibility of quantifying ultrasound myocardial perfusion studies based on the densitometric analysis of digital data and the (2) comparison of pulse inversion, second harmonic and harmonic power Doppler modalities with SPECT. METHODS AND RESULTS: Twenty-three patients with suspected ischaemic heart disease had i.v. injections of Tc-Sestamibi and Optison during a dipyridamole stress test for echocardiography in pulse inversion, second harmonic and harmonic power Doppler mode. Analysis was (a) visual by scoring and (b) quantitative by densitometry of digital data for background subtracted myocardial opacification (a.u.) and normalized contrast effect (%). In the nine control patients, myocardial opacification at stress was greater (P< or =0.002) than in the pathologic group (5. +/- 3.3 vs 2.6 +/- 2.5 a.u. in pulse inversion, 5.4 +/- 2.1 vs 2.4 +/- 1.8 in second harmonic and 7.1 +/- 3.7 vs 4.9 +/- 3.7 a.u. in harmonic power Doppler). In the pathologic group, normalized contrast effect decreased significantly during stress (23.7 +/- 18.8 to 11.3 +/- 10.8%, P<0.003) only in pulse inversion. Kappa values for patient based diagnostic agreement with SPECT were 0.75 by pulse inversion, 0.62 by second harmonic and 0.52 by harmonic power Doppler for quantitative analysis, and 0.51, 0.37 and 0.35 respectively, for visual assessment. CONCLUSION: Myocardial contrast echocardiography should be analysed using densitometry of digital data. The new technique pulse inversion demonstrates best agreement with SPECT data.

Albumins↗
PubMed2001

Neurogenesis in the central olfactory pathway of the adult shore crab Carcinus maenas is controlled by sensory afferents.

The number of olfactory projection neurons (OPNs) in the brain of the juvenile and adult shore crab Carcinus maenas continues to increase during the life of the animal. In vivo labeling of adult crabs with the proliferation marker bromodeoxyuridine (BrdU) revealed a group of proliferating neuronal precursor cells in the lateral soma clusters (LCs) and in the soma clusters of the hemiellipsoid bodies (HBCs). The LCs contain the cell bodies of the olfactory projection neurons and the HBCs house the cell bodies to which the OPNs project. The aim of the present study was to examine whether the input from primary olfactory afferents has any influence on the rate of proliferation and survival of the neuronal precursors in the central olfactory pathways of C. maenas. Different sets of experiments involving BrdU injection and its immunocytochemical detection combined with unilateral amputation of the antennule that houses the olfactory organ were carried out. Our results show that the missing olfactory sensory input affects the rate of proliferation and the survival of postmitotic cells in the LC and in the HBC compared with control animals. The effect on the survival of postmitotic cells tested by BrdU injection followed by unilateral ablation is lateralized. Proliferation of neuronal precursor cells tested by the reversed experimental order was drastically impaired bilaterally. We conclude that the olfactory sensory input is necessary for a normal rate of proliferation of neuronal precursors and the survival of their progeny in the LC and in the HBC of C. maenas.

Amputation, Surgical↗
PubMed2001

Perturbations in the impact of mutational activity on Vlambda genes in systemic lupus erythematosus.

To assess the impact of somatic hypermutation and selective influences on the Vlambda light chain repertoire in systemic lupus erythematosus (SLE), the frequency and pattern of mutations were analyzed in individual CD19+ B cells from a patient with previously undiagnosed SLE. The mutational frequency of nonproductive and productive rearrangements in the SLE patient was greater (3.1 x 10(-2) vs 3.4 x 10(-2), respectively) than that in normal B cells (1.2 x 10(-2) vs 2.0 x 10(-2), both P < 0.001). The frequencies of mutated rearrangements in both the nonproductive and productive repertoires were significantly higher in the patient with SLE than in normal subjects. Notably, there were no differences in the ratio of replacement to silent (R/S) mutations in the productive and nonproductive repertoires of the SLE patient, whereas the R/S ratio in the framework regions of productive rearrangements of normal subjects was reduced, consistent with active elimination of replacement mutations in this region. The pattern of mutations was abnormal in the SLE patient, with a significant increase in the frequency of G mutations in both the productive and nonproductive repertoires. As in normal subjects, however, mutations were found frequently in specific nucleotide motifs, the RGYW/WRCY sequences, accounting for 34% (nonproductive) and 46% (productive) of all mutations. These data are most consistent with the conclusion that in this SLE patient, the mutational activity was markedly greater than in normal subjects and exhibited some abnormal features. In addition, there was decreased subsequent positive or negative selection of mutations. The enhanced and abnormal mutational activity along with disturbances in selection may play a role in the emergence of autoreactivity in this patient with SLE.

B-Lymphocytes↗
PubMed2001

Roughness of crack interfaces in two-dimensional beam lattices.

The roughness of crack interfaces is reported in quasistatic fracture, using an elastic network of beams with random breaking thresholds. For strong disorders we obtain zeta = 0.86(3) for the roughness exponent, a result which is very different from the minimum energy surface exponent, i.e., zeta = 2 / 3. A crossover to lower values is observed as the disorder is reduced, the exponent in this regime being strongly dependent on the disorder.

Journal Article↗
PubMed2001

Unicellular cyanobacteria fix N2 in the subtropical North Pacific Ocean.

Fixed nitrogen (N) often limits the growth of organisms in terrestrial and aquatic biomes, and N availability has been important in controlling the CO2 balance of modern and ancient oceans. The fixation of atmospheric dinitrogen gas (N2) to ammonia is catalysed by nitrogenase and provides a fixed N for N-limited environments. The filamentous cyanobacterium Trichodesmium has been assumed to be the predominant oceanic N2-fixing microorganism since the discovery of N2 fixation in Trichodesmium in 1961 (ref. 6). Attention has recently focused on oceanic N2 fixation because nitrogen availability is generally limiting in many oceans, and attempts to constrain the global atmosphere-ocean fluxes of CO2 are based on basin-scale N balances. Biogeochemical studies and models have suggested that total N2-fixation rates may be substantially greater than previously believed but cannot be reconciled with observed Trichodesmium abundances. It is curious that there are so few known N2-fixing microorganisms in oligotrophic oceans when it is clearly ecologically advantageous. Here we show that there are unicellular cyanobacteria in the open ocean that are expressing nitrogenase, and are abundant enough to potentially have a significant role in N dynamics.

Atmosphere↗
PubMed2001

Thermodynamical implications of a protein model with water interactions.

We refine a protein model that reproduces fundamental aspects of protein thermodynamics. The model exhibits two transitions, hot and cold unfolding. The number of relevant parameters is reduced to three: (1) binding energy of folding relative to the orientational energy of bound water, (2) ratio of degrees of freedom between the folded and unfolded protein chain, and (3) the number of water molecules that can access the hydrophobic parts of the protein interior upon unfolding. By increasing the number of water molecules in the model, the separation between the two peaks in the heat capacity curve comes closer, which is more consistent with experimental data. In the end we show that if we, as a speculative assumption, assign only two distinct energy levels for the bound water molecules, better correspondence with experiments can be obtained.

Animals↗
PubMed2001

Distinguishing fractional and white noise in one and two dimensions.

We discuss the link between uncorrelated noise and the Hurst exponent for one- and two-dimensional interfaces. We show that long range correlations cannot be observed using one-dimensional cuts through two-dimensional self-affine surfaces whose height distributions are characterized by a Hurst exponent H lower than -1/2. In this domain, fractional and white noise are not distinguishable. A method analyzing the correlations in two dimensions is necessary. For H>-1/2, a crossover regime leads to an systematic overestimate of the Hurst exponent.

Journal Article↗
PubMed2001

Correlation between processing efficiency for ribonuclease P minimal substrates and conformation of the nucleotide -1 at the cleavage position.

It is demonstrated that acceptor stem duplexes derived from native tRNAs which contain a three-nucleotide extension at the 5'-terminus of mature tRNA are minimal substrates for ribonuclease P from both Escherichia coli and Bacillus subtilis. Variants with a cytidine at position -1 are most efficiently processed whereas the G -1 variant represents a comparatively poor substrate. An A -1 acceptor stem variant is a slightly better substrate than the G -1 variant though generally distinctly less efficient than the C -1 duplex. This is in qualitative agreement with the frequency of the occurrence of the corresponding nucleotides at position -1 in natural substrates, which is highest for pyrimidines and least for G. NMR analyses of the corresponding acceptor stems reveal that the conformation of the nucleotides at position -1 correlates with the substrate preferences of Ribonuclease P: Whereas C -1 adopts a conformation characterized by a glycosidic angle in the anti range (close to high-anti), the G -1 is clearly in syn conformation, and that of A -1 is intermediate between high-anti and syn. The riboses of nucleotides -1 are in all cases predominantly 2'-endo puckered.

Adenosine↗