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M T Madsen

Publications and source records attributed to M T Madsen.

At least 19 recordsLinked to original sources
PubMed2006

Relationship between bone strength and dual-energy X-ray absorptiometry measurements in pigs.

Computed tomography and a 3-point bending test were performed on the metacarpal bones of adult production pigs to test the hypothesis that bone strength is strongly correlated with areal bone mineral density (BMD) in this population. The aim of the study was to subject material from adult production pigs grouped by BMD to 3-point bending, to test this hypothesis and determine any correlations. In all, 168 individual computed tomography scans and mechanical tests were performed on the collected material. For evaluation purposes, the material was divided into the categories low, medium, and high BMD (<1, 1 to 1.4, and >1.4 g/cm(2), respectively). The results showed a difference in the maximum load, in the stress at maximum load, and stiffness among each BMD group (P < 0.001) and in elastic modulus between the low BMD group and the 2 other groups (P < 0.001). A correlation between both intrinsic and extrinsic measures of bone strength and BMD was thus demonstrated. The projected change in each of the variables reported, for a 0.1 g/cm(2) alteration in BMD (within the BMD range evaluated in this study), is as follows: maximum load, 708 N; stress at maximum load, 50 N/mm(2); stiffness, 391.6 N/mm; and elastic modulus, 108 N/mm(2) (P < 0.001). The results confirm the relationship between BMD and bone strength and indicate that BMD screening can be used in fracture risk assessments in production pigs.

Absorptiometry, Photon↗
PubMed2005

Factors regulating ovarian function in pigs.

The hormonal interactions of the hypothalamic-pituitary-ovarian-uterine axis are accountable for a normal reproduction in female pigs. It is of importance to have knowledge of estrous symptoms and hormonal profiles around ovulation. The introduction of the transrectal ultrasonography in sows has given us the possibility to study ovarian activity in conscious animals and relate the timing of estrus to ovulation. Combining this technique with measuring of several hormones like luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin, estradiol, progesterone, insulin-like growth hormone I (IGF-I), prostaglandin F2alpha (PGF2alpha) metabolite, oxytocin, facilitate our knowledge about the sequence of ovarian events. Evidence suggests that activation of the hypothalamic-pituitary-adrenal axis may hamper the normal gonadotropin secretion and in consequence, the ovarian function. The metabolic status during lactation, weaning of piglets and social stress might affect onset of ovarian activity and the related estrous behavior. The role of seminal plasma, artificial insemination and presence of the boar might also be included as factors regulating the temporal kinetics of ovulation, corpus luteum development, uterine function and steroid production in the ovary. Studies using a simulated stress by means of adrenocorticotrophic hormone (ACTH) administration or food deprivation are tools in understanding how the ovary is susceptible to impairment. The intention of this paper is to review current knowledge concerning the endocrine aspects of normal and stress-influenced ovarian function in pigs.

Animals↗
PubMed2001

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Fluorodeoxyglucose F18↗
PubMed2000

X-ray attenuation coefficients of high-atomic-number, hexanuclear transition metal cluster compounds: a new paradigm for radiographic contrast agents.

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the radiologic attenuation properties of the parent cluster compounds, particularly attenuation as a function of discrete photon energy, before investigating ligand substitutions, which are necessary to improve cluster biocompatibility and to impart desirable physicochemical properties. MATERIALS AND METHODS: The linear attenuation coefficients for solutions of the cluster compounds Ta6Br14, K8Ta6O19, and (H3O)2W6Cl14 were determined at 60, 80, 103, 122, and 140 keV from gamma-ray transmission measurements with americium-241, xenon-133, gadolinium-153, cobalt-57, and technetium-99m radioactive sources. Transmission measurements were obtained for a fixed time interval that ensured a statistically accurate count distribution exceeding 20,000 counts through the sample for each trial. RESULTS: On a strictly mole per liter basis, a 0.075 mol/L aqueous solution of K8Ta6O19 showed 1.08 times the attenuation of 0.063 mol/L aqueous iohexol at 60 keV and 3.30 times the attenuation at 80 keV. Similarly, a 0.05 mol/L methanolic solution of (H3O)2W6Cl4 showed 0.96 times (96%) the attenuation of 0.063 mol/L aqueous iohexol at 60 keV but 3.09 times the attenuation of the iohexol solution at 80 keV. Attenuations of 0.063 mol/L aqueous iohexol and 0.0125 mol/L Ta6Br14 (ie, at approximately one-fifth the iohexol concentration) were comparable at greater than 60 keV. CONCLUSION: These results confirm the theoretic potential for use of early transition metal cluster compounds as radiographic contrast agents. At higher x-ray energies, cluster compounds demonstrate multiplied x-ray attenuation relative to iodinated contrast agents.

Contrast Media↗
PubMed2000

A threshold method to improve standardized uptake value reproducibility.

Although standardized uptake values (SUV) are widely used to quantify the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours, there are systematic differences in the way this index is applied by different investigators. The aims of this study were to compare the effects of using maximum or mean region counts in the calculation of SUV and to investigate an alternative technique based on a fixed fraction of the maximum counts. Simulated PET projections of the thorax were generated together with spherical lesions that varied in diameter from 1.6 to 4.8 cm with uptake values of 2, 4 and 8. The lesion SUVs were determined using either the maximum (SUVmax) or mean count (SUVmean) values found in regions circumscribing the lesion. In addition, average values were calculated that only included region pixels that exceeded a selected fraction of maximum value (SUV0.6max or SUV0.75max). These methods were also applied to six clinical 18F-FDG PET studies with a total of 12 lesions. The SUVs for these lesions were determined independently by four observers. Decreases with respect to SUVmax of 57%, 23% and 14% were found for SUVmean, SUV0.6max and SUV0.75max approaches respectively in the simulation study. The variation in SUVmean with region size was 35%, while the SUV0.6max and SUV0.75max was less than 3%. Similar results were obtained for the clinical data. We conclude that the proposed technique produces SUVs that are essentially independent of lesion region size and shape. It is expected that this will provide a more stable and reliable result than current approaches.

Adult↗
PubMed1999

The human antibacterial cathelicidin, hCAP-18, is bound to lipoproteins in plasma.

Cathelicidins are a family of antibacterial and lipopolysaccharide-binding proteins. hCAP-18, the only human cathelicidin, is a major protein of the specific granules of human neutrophils. The plasma level of hCAP-18 is >20-fold higher than that of other specific granule proteins relative to their levels within circulating neutrophils. The aim of this study was to elucidate the background for this high plasma level of hCAP-18. Plasma was subjected to molecular sieve chromatography, and hCAP-18 was found in distinct high molecular mass fractions that coeluted with apolipoproteins A-I and B, respectively. The association of hCAP-18 with lipoproteins was validated by the cofractionation of hCAP-18 with lipoproteins using two different methods for isolation of lipoproteins from plasma. Furthermore, the level of hCAP-18 in delipidated plasma was <1% of that in normal plasma. Immunoprecipitation of very low, low, and high density lipoprotein particles with anti-apolipoprotein antibodies resulted in coprecipitation of hCAP-18. The binding of hCAP-18 to lipoproteins was mediated by the antibacterial C-terminal part of the protein. The binding of hCAP-18 to lipoproteins suggests that lipoproteins may play an important role as a reservoir of this antimicrobial protein.

Amino Acid Sequence↗
PubMed1999

Removal of N-terminal polyhistidine tags from recombinant proteins using engineered aminopeptidases.

We have developed a specific and efficient method for complete removal of polyhistidine purification tags (HisTags) from the N-termini of target proteins. The method is based on the use of the aminopeptidase dipeptidyl peptidase I (DPPI), either alone or in combination with glutamine cyclotransferase (GCT) and pyroglutamyl aminopeptidase (PGAP). In both cases, the HisTag is cleaved off by DPPI, which catalyzes a stepwise excision of a wide range of dipeptides from the N-terminus of a peptide chain. Some sequences, however, are resistant to DPPI cleavage and a number of mature proteins have nonsubstrate N-termini which protects them against digestion. For such proteins, HisTags composed of an even number of residues can be cleaved off by treatment with DPPI alone. When the target protein is unprotected against DPPI, a blocking group is generated enzymatically from a glutamine residue inserted between the HisTag and the target protein. A protein with a HisTag-Gln extension is incubated with both DPPI and GCT. As above, the polyhistidine sequence is cleaved off by DPPI, but when the glutamine residue appears in the N-terminus, it is immediately converted into a pyroglutamyl residue by an excess of GCT and further DPPI digestion is prevented. The desired sequence is finally obtained by excision of the pyroglutamyl residue with PGAP. All the enzymes employed can bind to immobilized metal affinity chromatography (IMAC) matrices, and in this paper we demonstrate a simple and highly effective process combining IMAC purification of His-tagged proteins, our aminopeptidase-based method for specific excision of HisTags and use of subtractive IMAC for removing processing enzymes. Typical recoveries were 75-90% for the enzymatic processing and subtractive IMAC. The integrated process holds promises for use in large-scale production of pharmaceutical proteins because of a simple overall design, use of robust and inexpensive matrices, and use of enzymes of either recombinant or plant origin.

Amino Acid Sequence↗
PubMed1999

Pulmonary CT image classification with evolutionary programming.

RATIONALE AND OBJECTIVES: It is often difficult to classify information in medical images from derived features. The purpose of this research was to investigate the use of evolutionary programming as a tool for selecting important features and generating algorithms to classify computed tomographic (CT) images of the lung. MATERIALS AND METHODS: Training and test sets consisting of 11 features derived from multiple lung CT images were generated, along with an indicator of the target area from which features originated. The images included five parameters based on histogram analysis, 11 parameters based on run length and co-occurrence matrix measures, and the fractal dimension. Two classification experiments were performed. In the first, the classification task was to distinguish between the subtle but known differences between anterior and posterior portions of transverse lung CT sections. The second classification task was to distinguish normal lung CT images from emphysematous images. The performance of the evolutionary programming approach was compared with that of three statistical classifiers that used the same training and test sets. RESULTS: Evolutionary programming produced solutions that compared favorably with those of the statistical classifiers. In separating the anterior from the posterior lung sections, the evolutionary programming results were better than two of the three statistical approaches. The evolutionary programming approach correctly identified all the normal and abnormal lung images and accomplished this by using less features than the best statistical method. CONCLUSION: The results of this study demonstrate the utility of evolutionary programming as a tool for developing classification algorithms.

Algorithms↗
PubMed1998

Active recombinant rat dipeptidyl aminopeptidase I (cathepsin C) produced using the baculovirus expression system.

An active form of rat dipeptidyl aminopeptidase I (DPPI, cathepsin C) was obtained by heterologous expression in insect cells. Baculoviruses carrying a cDNA sequence encoding the entire rat DPPI precursor was used to infect High Five cells in a serum-free medium. Recombinant DPPI (rDPPI) was secreted into the medium from which it was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography (HIC), and ion-exchange chromatography. A polyhistidine-tagged form of the enzyme (HT-rDPPI) was purified from the medium by immobilized metal affinity chromatography (IMAC). In vivo activation of native rat DPPI involves at least three chain cleavages per subunit and the ability of the expression system to imitate this processing was investigated. Both rDPPI and HT-rDPPI were secreted into the medium as unprocessed and inactive proenzymes and gradually converted into their active forms in the medium. This process was not completed at the time of harvest but mature enzyme processed similarly to native rat and human DPPI could be obtained by incubating the eluates from the HIC and IMAC columns at pH 4.5 and 5 degrees C for 18-40 h. The yield of purified and matured enzyme was approximately 50 mg/liter, and it was shown that rDPPI and HT-rDPPI were active against both a dipeptide-p-nitroanilide substrate and human growth hormone N-terminally extended with an Ala-Glu dipeptide.

Animals↗
PubMed1998

Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats.

The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats. Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction of leukaemic cells increased to > 90% and the pH dropped to about 6.5. The fraction of NITP+ cells increased to > 80% in bone marrow and to about 40% in blood. The fraction of BrdUrd+ cells was unchanged in blood, but decreased in bone marrow both for normal cells (from about 20% to 5%), and for leukaemic cells (from about 45% to 25%), evidently as a result of the severely changed microenvironment. In this study we have demonstrated in vivo the development of an acidic and hypoxic bone marrow hampering normal haemopoiesis during leukaemic growth. Our data support the notion of BNML as a valuable tool for studying leukaemogenesis.

Acute Disease↗
PubMed1997

A method for quantifying SPECT uniformity.

Field uniformity is an important parameter for monitoring the performance of SPECT imaging systems. However, it is difficult to apply objective measures of uniformity because of the large variance associated with reconstructed images. In the proposed method, annular sampling of the SPECT uniformity image is used to reduce the noise level without decreasing the magnitude of uniformity artifacts. The reconstructed uniformity image is sectioned into annular rings centered on the center of rotation to match the expected distribution of uniformity artifacts. Statistical fluctuations are reduced by averaging the counts within the annular rings, allowing the use of objective measures of field uniformity such as integral uniformity. Application of the annular sampling technique on simulated and phantom uniformity images showed that the technique could reliably quantify SPECT uniformity artifacts at acceptable count levels. As a result this method can be used to objectively evaluate SPECT field uniformity in systems which utilize parallel collimation and circular orbits.

Biometry↗
PubMed1996

The primary structure and enzymic properties of porcine prochymosin and chymosin.

Preliminary investigations by N-terminal sequence analysis showed that pig and calf chymosin possessed 80% amino acid sequence identity but showed considerable differences in their enzymatic properties. A comparison of their structures may therefore contribute to an understanding of the significance of the amino acid residues responsible for the differences in these properties. Pig chymosis was extracted from the stomachs of pigs of less than 3 weeks of age, and was purified by ion exchange chromatography. Half of the primary structure was determined by amino acid sequencing and the complete structure was deduced from a cloned chymosin cDNA. Results showed that the zymogen showed 81% sequence identity with calf prochymosin and 57% identity with pig pepsinogen A. The size of the propart and location of the residue which becomes the N-terminus in the active molecule were the same in the prochymosins. The maximum general proteolytic activity at pH 3.5 of pig chymosin was 2-3% of that of the activity of pig pepsin A at pH 2, whereas the milk clotting activity relative to the general proteolytic activity of pig chymosin was much higher than that of calf chymosin. Agar gel electrophoresis at pH 5.3 of stomach extracts of individual pigs showed the existence of two predominant genetic variants of zymogen and enzyme. The two variants could not be distinguished by amino acid composition or N-terminal sequencing, and no differences in the enzymatic properties of the genetic variants were observed. It was concluded that of the residues that participate in the substrate binding, calf and pig chymosin differ in the following positions (pig pepsin numbering, subsites in parentheses): Ser 12 Thr (S4), Leu 30 Val (S1/S3), His 74 Gln (S'2), Val 111 Ile (S1/S3), Lys 220 Met (S4). With regard to the low general proteolytic activity of pig chymosin, the substitution Asp 303 Val relative to calf chymosin may contribute to an explanation of this.

Amino Acid Sequence↗
PubMed1995

Blocking of tissue factor pathway inhibitor (TFPI) shortens the bleeding time in rabbits with antibody induced haemophilia A.

Tissue factor (TF)/FVIIa initiates coagulation by activating factor IX (FIX) and factor X (FX). Tissue factor pathway inhibitor (TFPI)-FXa complexes form and inhibit TF/FVIIa. Blocking of TFPI may facilitate haemostasis initiated by FVIIa/TF thereby compensating for impaired FIX/FVIII-dependent coagulation. This hypothesis was tested in a study using rabbits made temporarily haemophilic by the injection of antibodies against FVIII. These rabbits were given i.v. injections of anti-TFPI IgG antibodies and 40 min later bleeding was initiated by cutting the nail including the apex of the cuticle. Injection of anti-TFPI IgG shortened the bleeding time significantly from 26 min to 11 min (normal mean bleeding time in non-haemophilia rabbits: 5 min). Treatment with anti-TFPI IgG also resulted in a shortening of the haemophilic aPTT to a level slightly longer than the normal aPTT. In addition, the prolonged dilute TF clotting time was shortened by the anti-TFPI IgG treatment. Thus, both bleeding and coagulation parameters indicated that blocking of TFPI may be potentially haemostatic in haemophilia.

Animals↗
PubMed1995

Quantitation of SPECT performance: Report of Task Group 4, Nuclear Medicine Committee.

A comprehensive performance testing program is an essential ingredient of high-quality single-photon emission computed tomography (SPECT). Many of the procedures previously published are complicated, time consuming, or require a special testing environment. This Task Group developed a protocol for evaluating SPECT imaging systems that was simple, practical, required minimal test equipment, and could be performed in a few hours using processing software available on all nuclear medicine computers. It was designed to test rotational stability of uniformity and sensitivity, tomographic spatial resolution, uniformity and contrast, and the accuracy of attenuation correction. It can be performed in less than three hours and requires only a Co-57 flood source, a line source, and a tomographic cylindrical phantom. The protocol was used 51 times on 42 different cameras (seven vendors) by four different individuals. The results were used to establish acceptable ranges for the measured parameters. The variation between vendors was relatively small and appeared to reflect slight differences in basic camera performance, collimation, and reconstruction software. Individuals can use the tabulated values to evaluate the performance of individual systems.

Cobalt Radioisotopes↗
PubMed1995

The AAPM/RSNA physics tutorial for residents. Introduction to emission CT.

The article explores the fundamentals of emission computed tomography (CT) from a nonmathematical approach. Tomographic images reveal the internal distributions of radioactivity in three-dimensional objects, and thus allows anatomic localization and improves contrast. Tomography requires a stable distribution of radionuclides, uniform detector response, an accurate center of rotation, and a complete set of projections. In emission CT, a large number of measurements, called projections, are collected at various angles about the patient during the examination. This information is organized by the angles of acquisition into a stack, called a sinogram. Each projection is modified by applying a reconstruction filter (eg, ramp or windowed reconstruction filters). These modified projections are backprojected to form the transverse tomographic images. The quality of tomographic images generated from filtered backprojection depends on the underlying assumptions about the projections. Typical artifacts that result from violations of these assumptions include motion, uniformity, and attenuation artifacts. In addition, an inaccurate center of rotation, insufficient angular sampling, and errors in selection of pixel size can result in poor-quality reconstructed images.

Artifacts↗
PubMed1995

Cranial osteomyelitis: diagnosis and follow-up with In-111 white blood cell and Tc-99m methylene diphosphonate bone SPECT, CT, and MR imaging.

PURPOSE: To assess the usefulness of indium-111 white blood cell and technetium-99m methylene diphosphonate bone single photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging in cranial osteomyelitis. MATERIALS AND METHODS: Twenty-six cases (25 patients: 13 male, 12 female; mean age, 55 years) of suspected osteomyelitis were evaluated. Sixteen were postoperative. Final diagnosis was established by means of bone culture in 18 cases and clinical follow-up in eight. RESULTS: Of 35 CT scans, 10 were true-positive (TP); three false-negative (FN); 13, true-negative (TN); one, false-positive (FP); and eight, equivocal. Of 36 SPECT scans, 19 were TP; 13, TN; one, FP; one, FN; and two, equivocal. Of 11 MR images four were TP; five, TN; and two, FN. CONCLUSION: CT is best for differentiation between soft-tissue and bone infection. MR imaging is best for assessment of the calvaria and skull base. SPECT is best for assessment of altered bone and may be the best technique for follow-up.

Adolescent↗
PubMed1995

Scintigraphic evaluation of small bowel transit in healthy subjects: inter- and intrasubject variability.

OBJECTIVES: This study was performed to evaluate inter- and intrasubject variability of small bowel transit time and the effect of age and sex on transit in the small bowel. METHODS: Ten young subjects (five females) and nine elderly subjects (four females) were studied. Small bowel transit time was assessed by scintigraphic method using 99mtechnetium-sulfur colloid-labeled eggs. To evaluate intrasubject variability, 10 subjects underwent a second study on a later occasion. RESULTS: Mean small bowel transit time was 220.9 +/- 49 min with a range of 131 to 322 min, with no significant difference between the young and elderly groups or between sexes. There was a good intraobserver and interobserver reproducibility within the same test (r = 0.92 and r = 0.85, respectively). There was a significant biological variability between the first and the second studies, which was true whether the studies were processed independently (r = 0.43) or whether identical regions of interest were applied (r = 0.50). CONCLUSION: The normal range of small bowel transit time is wide in normal subjects; and there is a significant intrasubject biological variability for small bowel transit time. These findings should be kept in mind when using scintigraphic techniques for assessment of patients with motility disorders or when using the test repeatedly in the same subject in the evaluation of therapeutic measures. The results do not seem to be affected by age or sex.

Adult↗