Showing papers by "Katholieke Universiteit Leuven published in 1997"

Multimodality image registration by maximization of mutual information

Abstract: A new approach to the problem of multimodality medical image registration is proposed, using a basic concept from information theory, mutual information (MI), or relative entropy, as a new matching criterion. The method presented in this paper applies MI to measure the statistical dependence or information redundancy between the image intensities of corresponding voxels in both images, which is assumed to be maximal if the images are geometrically aligned. Maximization of MI is a very general and powerful criterion, because no assumptions are made regarding the nature of this dependence and no limiting constraints are imposed on the image content of the modalities involved. The accuracy of the MI criterion is validated for rigid body registration of computed tomography (CT), magnetic resonance (MR), and photon emission tomography (PET) images by comparison with the stereotactic registration solution, while robustness is evaluated with respect to implementation issues, such as interpolation and optimization, and image content, including partial overlap and image degradation. Our results demonstrate that subvoxel accuracy with respect to the stereotactic reference solution can be achieved completely automatically and without any prior segmentation, feature extraction, or other preprocessing steps which makes this method very well suited for clinical applications.

A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.

Abstract: Background Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. Methods We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. Results At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p Conclusions A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.

Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene

Abstract: Human obesity has an inherited component, but in contrast to rodent obesity, precise genetic defects have yet to be defined. A mutation of carboxypeptidase E (CPE), an enzyme active in the processing and sorting of prohormones, causes obesity in the fat/fat mouse. We have previously described a women with extreme childhood obesity (Fig. 1), abnormal glucose homeostasis, hypogonadotrophic hypogonadism, hypocortisolism and elevated plasma proinsulin and pro-opiomelanocortin (POMC) concentrations but a very low insulin level, suggestive of a defective prohormone processing by the endopeptidase, prohormone convertase 1 (PC1; ref. 4). We now report this proband to be a compound heterozygote for mutations in PC1. Gly-->Arg483 prevents processing of proPC1 and leads to its retention in the endoplasmic reticulum (ER). A-->C+4 of the intro-5 donor splice site causes skipping of exon 5 leading to loss of 26 residues, a frameshift and creation of a premature stop codon within the catalytic domain. PC1 acts proximally to CPE in the pathway of post-translational processing of prohormones and neuropeptides. In view of the similarity between the proband and the fat/fat mouse phenotype, we infer that molecular defects in prohormone conversion may represent a generic mechanism for obesity, common to humans and rodents.

Meta-analyses of age–cognition relations in adulthood: Estimates of linear and nonlinear age effects and structural models.

Abstract: A meta-analysis was conducted on 91 studies to derive a correlation matrix for adult age, speed of processing, primary-working memory, episodic memory, reasoning, and spatial ability. Structural equation modeling with a single latent common cognitive factor showed that all cognitive measures shared substantial portions of age-related variance. A mediational model revealed that speed of processing and primary-working memory appear to be important mediators of age-related differences in the other measures. However, not all of the age-related influences were mediated. An examination of quadratic age effects and correlational patterns for subsamples under and over 50 years of age revealed that (a) negative age-cognition relations were significant for the 18- to 50-year-old sample and (b) the age-related decline accelerated significantly over the adult life span for variables assessing speed, reasoning, and episodic memory.

The Block Cipher Square

Abstract: In this paper we present a new 128-bit block cipher called Square. The original design of Square concentrates on the resistance against differential and linear cryptanalysis. However, after the initial design a dedicated attack was mounted that forced us to augment the number of rounds. The goal of this paper is the publication of the resulting cipher for public scrutiny. A C implementation of Square is available that runs at 2.63 MByte/s on a 100 MHz Pentium. Our M68HC05 Smart Card implementation fits in 547 bytes and takes less than 2 msec. (4 MHz Clock). The high degree of parallellism allows hardware implementations in the Gbit/s range today.

Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation

Abstract: The molecular mechanisms predisposing to atherosclerotic aneurysm formation remain undefined(1-5). Nevertheless, rupture of aortic aneurysms is a major cause of death in Western societies, with few available treatments and poor long-term prognosis. Indirect evidence suggests that matrix metalloproteinases (MMPs) and plasminogen activators (PAs) are involved in its pathogenesis (1,6-12). MMPs are secreted as inactive zymogens (pro-MMPs), requiring activation in the extracellular compartment(11,13). Plasmin, generated from the zymogen plasminogen by tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA; refs 14,15), has been proposed as a possible activator in vitro, but evidence for such a role in vivo is lacking(16,17) . Analysis of atherosclerotic aorta in mice with a deficiency of apoliprotein E (Apoe(-/-);ref. 18), singly or combined with a deficiency of t-PA (Apoe(-/-):Plat(-/-)) or of u-PA (Apoe(-/-):Plau(-/-); ref. 19), indicated that deficiency of u-PA protected against media destruction and aneurysm formation, probably by means of reduced plasmin-dependent activation of pro-MMPs. This genetic evidence suggests that plasmin is a pathophysiologically significant activator of pro-MMPs in vivo and may have implications for the design of therapeutic strategies to prevent aortic-wall destruction by controlling Plau gene function.

Antimicrobial Peptides from Plants

Abstract: Peptides with antimicrobial properties are present in most if not all plant species All plant antimicrobial peptides isolated so far contain even numbers of cysteines (4, 6, or 8), which are all pairwise connected by disulfide bridges, thus providing high stability to the peptides Based on homologies at the primary structure level, plant antimicrobial peptides can be classified into distinct families including thionins, plant defensins, lipid transfer proteins, and he vein- and knottin-type antimicrobial peptides Detailed three-dimensional structure information has been obtained for one or more members of these peptide families All antimicrobial peptides studied thus far appear to exert their antimicrobial effect at the level of the plasma membrane of the target microorganism, but the different peptide types are likely to act via different mechanisms Antimicrobial peptides can occur in all plant organs In unstressed organs, antimicrobial peptides are usually most abundant in the outer cell

Intrinsic SiC/SiO2 Interface States

Abstract: The energy distribution of electron states at SiC/SiO 2 interfaces produced by oxidation of various (3C, 4H, 6H) SiC polytypes is studied by electrical analysis techniques and internal photoemission spectroscopy. A similar distribution of interface traps over the SiC bandgap is observed for different polytypes indicating a common nature of interfacial defects. Carbon clusters at the SiC/SiO 2 interface and near-interfacial defects in the SiO 2 are proposed to be responsible for the dominant portion of interface traps, while contributions caused by dopant-related defects and dangling bonds at the SiC surface are not observed.

Identification of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene. The European Consortium on MEN1

Abstract: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by tumours of the parathyroids, pancreas and anterior pituitary that represents one of the familial cancer syndromes. The MEN1 locus has been previously localised to chromosome 11q13, and a <300 kb gene-rich region flanked centromerically by PYGM and telomerically by D11S1783 defined by combined meiotic and tumour deletion mapping studies. Two candidate genes, ZFM1 and PPP2R5B, from this region have been previously excluded, and in order to identify additional candidate genes we used a BAC to isolate cDNAs from a bovine parathyroid cDNA library by direct selection. One of the novel genes that we identified, SCG2, proved to be identical to the recently published MEN1 gene, which is likely to be a tumour suppressor gene. The SCG2 transcript was 2.9 kb in all tissues with an additional 4.2 kb transcript also being present in the pancreas and thymus. Mutational analysis of SCG2 in 10 unrelated MEN1 families identified one polymorphism and nine different heterozygous mutations (one missense, four non-sense, one insertional and three deletional frameshifts) that segregated with the disease, hence providing an independent confirmation for the identification of the MEN1 gene.

A 1.8-GHz low-phase-noise CMOS VCO using optimized hollow spiral inductors

Abstract: A completely integrated 1.8-GHz low-phase-noise voltage-controlled oscillator (VCO) has been realized in a standard silicon digital CMOS process. The design relies heavily on the integrated spiral inductors which have been realized with only two metal layers and without etching. The effects of high-frequency magnetic fields and losses in the heavily doped substrate have been simulated and modeled with finite-element analysis. The achieved phase noise is as low as -116 dBc/Hz at an offset frequency of 600 kHz, at a power consumption of only 6 mW. The VCO is tuned with standard available junction capacitances, resulting in a 250-MHz tuning range.

The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation

Abstract: The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae. Previous studies showed that GPD1 plays a role in osmoadaptation since its expression is induced by osmotic stress and gpd1 delta mutants are osmosensitive. Here we report that GPD2 has an entirely different physiological role. Expression of GPD2 is not affected by changes in external osmolarity, but is stimulated by anoxic conditions. Mutants lacking GPD2 show poor growth under anaerobic conditions. Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions. This growth inhibition, which is accompanied by a strong intracellular accumulation of NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of NADH. Thus, glycerol formation is strictly required as a redox sink for excess cytosolic NADH during anaerobic metabolism. The anaerobic induction of GPD2 is independent of the HOG pathway which controls the osmotic induction of GPD1. Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde. We conclude that expression of GPD2 is controlled by a novel, oxygen-independent, signalling pathway which is required to regulate metabolism under anoxic conditions.

Optimal robot excitation and identification

Abstract: This paper discusses experimental robot identification based on a statistical framework. It presents a new approach toward the design of optimal robot excitation trajectories, and formulates the maximum-likelihood estimation of dynamic robot model parameters. The differences between the new design approach and the existing approaches lie in the parameterization of the excitation trajectory and in the optimization criterion. The excitation trajectory for each joint is a finite Fourier series. This approach guarantees periodic excitation which is advantageous because it allows: 1) time-domain data averaging; 2) estimation of the characteristics of the measurement noise, which is valuable in the case of maximum-likelihood parameter estimation. In addition, the use of finite Fourier series allows calculation of the joint velocities and acceleration in an analytic way from the measured position response, and allows specification of the bandwidth of the excitation trajectories. The optimization criterion is the uncertainty on the estimated parameters or a lower bound for it, instead of the often used condition of the parameter estimation problem. Simulations show that this criterion yields parameter estimates with smaller uncertainty bounds than trajectories optimized according to the classical criterion. Experiments on an industrial robot show that the presented trajectory design and maximum-likelihood parameter estimation approaches complement each other to make a practicable robot identification technique which yields accurate robot models.

Accelerated collagen-induced arthritis in IFN-gamma receptor-deficient mice.

Abstract: Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis. Here, we describe experiments showing that IFN-gamma receptor knockout (IFN-gammaR alpha KO) mice of the DBA/1 strain develop CIA more readily than their wild-type counterparts. Symptoms of disease started 10 days earlier and the cumulative incidence of arthritis was significantly higher in the mutant mice than in wild-type mice. Similarly, accelerated onset of the disease was also found in wild-type DBA/1 mice treated with neutralizing mAbs against IFN-gamma. Histologic examination of the joints revealed a massive infiltration of the synovium with mononuclear cells and neutrophils, hyperplasia, and severe pannus formation in IFN-gammaR alpha KO mice when such inflammatory lesions were not yet detectable in wild-type mice. Serum levels of anti-collagen type II Abs, including total IgG and IgM, as well as IgG1, IgG2a, and IgG2b isotypes were found to be lower in the mutant mice. IL-2 and IL-4 remained undetectable in sera of both groups of mice, but did appear in the circulation after anti-CD3 Ab challenge. Significantly higher IL-2 and lower IL-4 serum levels were found in anti-CD3-challenged IFN-gammaR alpha KO mice than in wild-type counterparts, both at an early and at a later stage of the disease. These observations indicate that endogenous IFN-gamma counteracts development of collagen-induced arthritis and suggest that IFN-gamma does so by up-regulating IL-4 production and/or down-regulating IL-2 production. The data are in line with the concept of a pathogenic role of Th1-type cellular immunity in CIA in spite of a decreased Ab response to collagen type II.

Muscle weakness is related to utilization of health care resources in COPD patients

Abstract: The factors determining utilization of health care resources in patients with chronic obstructive pulmonary disease (COPD) are poorly understood. In order to obtain insight into these factors, we studied the utilization of health care resources in 57 stable COPD patients with a forced expiratory volume in one second (FEV1) of 36 +/- 9% predicted. Patients were divided into two groups: admitted at least twice in the last year (high medical consumption; n = 23) or not admitted in the last year (low medical consumption; n = 34). Other variables related to utilization of health care resources studied were; the number of hospital days; the number of out-patient visits to a pulmonary department in the last year; and the average daily dose (ADD) of corticosteroids taken in the last 6 months. The actual cost of utilization of health care resources, however, was not studied. In addition, pulmonary function, serum electrolytes, blood gas values, 6 min walking distance, respiratory and peripheral muscle force, and appraisal of self-care agency (ASA score) were studied. Pulmonary function, serum electrolytes, blood gas values, ASA score and walking distance were not different between the two groups (e.g. FEV1 36 +/- 8 vs 36 +/- 10% pred). Respiratory muscle forces tended to be lower in the high medical consumption group, this tendency almost reaching statistical significance for maximal expiratory pressure (PE,max) (p = 0.08). Peripheral muscle force, however, was clearly reduced in the high medical consumption group (quadriceps force 63 +/- 20 vs 82 +/- 26% pred; p < 0.05). The number of admissions, the number of hospital days, the number of out-patient visits, and ADD were interrelated and also related to ventilatory and peripheral muscle force (r -0.18 to -0.38). This relationship was statistically significant for PE,max, whilst a similar tendency was present for maximal inspiratory pressure (PI,max). In stepwise multiple regression analysis, only quadriceps force was a significant determinant of utilization of health care services. We conclude that utilization of health care services in patients with chronic obstructive pulmonary disease is related to ventilatory and peripheral muscle force. Whether or not reduced muscle force is simply an expression of disease severity remains to be determined.

Germline Mutations in the PTEN/MMAC1 Gene in Patients With Cowden Disease

Abstract: Cowden disease, also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome with a high risk of breast and thyroid cancer. The gene involved has been localized to chromosome 10q22-23. Recently, the tumour suppressor gene PTEN/MMAC1, encoding a putative protein tyrosine or dual-specificity phosphatase, was cloned from that region and three mutations were detected in patients with Cowden disease. We confirmed that the PTEN/MMAC1 gene is indeed the gene for Cowden disease by a refined localization of the gene to the interval between D10S1761 and D10S541, which contains the PTEN/MMAC1 gene and, by mutation analysis in eight unrelated familial and 11 sporadic patients with Cowden disease. Eight different mutations were detected in various regions of the PTEN/MMAC1 gene. One mutation was detected twice. All detected changes in the gene can be predicted to have a very deleterious effect on the putative protein. Five of the nine patients have a mutation in exon 5 coding for the putative active site and flanking amino acids. Evaluation of the clinical data of the patients in which a mutation could be detected gives no clear indications for a correlation between the genotype and phenotype. In 10 patients no mutation could be detected so far. In support of the linkage data, no evidence has emerged from the phenotype of these patients suggestive for genetic heterogeneity.

Long-term creatine intake is beneficial to muscle performance during resistance training

Abstract: Vandenberghe, K., M. Goris, P. Van Hecke, M. Van Leemputte, L. Vangerven, and P. Hespel. Long-term creatine intake is beneficial to muscle performance during resistance training.J. Appl. Physiol. 8...

Syntenin, a PDZ protein that binds syndecan cytoplasmic domains

Abstract: The syndecans are transmembrane proteoglycans that place structurally heterogeneous heparan sulfate chains at the cell surface and a highly conserved polypeptide in the cytoplasm. Their versatile heparan sulfate moieties support various processes of molecular recognition, signaling, and trafficking. Here we report the identification of a protein that binds to the cytoplasmic domains of the syndecans in yeast two-hybrid screens, surface plasmon resonance experiments, and ligand-overlay assays. This protein, syntenin, contains a tandem repeat of PDZ domains that reacts with the FYA C-terminal amino acid sequence of the syndecans. Recombinant enhanced green fluorescent protein (eGFP)–syntenin fusion proteins decorate the plasmamembrane and intracellular vesicles, where they colocalize and cosegregate with syndecans. Cells that overexpress eGFP–syntenin show numerous cell surface extensions, suggesting effects of syntenin on cytoskeleton–membrane organization. We propose that syntenin may function as an adaptor that couples syndecans to cytoskeletal proteins or cytosolic downstream signal-effectors.

The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk

Abstract: Objective This meta-analysis attempted to derive pooled estimates for the associations between various cardiovascular-renal disorders and the deletion/insertion (D/l) polymorphism of the angiotensin converting enzyme (ACE) gene. Methods Case-control studies were combined, using the Mantel-Haenszel approach. Joint P values for continuous variables were calculated by Stouffer's method. Continuous measurements reported in different units were expressed on a percentage scale using the within-study mean of the II genotype as the denominator. Results The computerized database used for this analysis included 145 reports with an overall sample size of 49 959 subjects. Overall, possession of the D allele was associated with an increased risk of atherosclerotic and renal microvascular complications. In comparison with the II reference group, the excess risk in DD homozygotes (P < 0.001) was 32% for coronary heart disease (CHD; 30 studies), 45% for myocardial infarction (20 studies), 94% for stroke (five studies) and 56% for diabetic nephropathy (11 studies). The corresponding risk in Dl heterozygotes amounted to 11% (P = 0.02), 13% (P = 0.02), 22% (P = 0.10) and 40% (P < 0.001), respectively. Hypertension (23 studies), left ventricular hypertrophy (five studies), hypertrophic or dilated cardiomyopathy (eight studies) and diabetic retinopathy (two studies) were not related to the Dl polymorphism. Publication bias was observed for CHD, myocardial infarction and microvascular nephropathy, but not hypertension. In studies with DNA amplification in the presence of insertion-specific primers, the risk associated with the DD genotype increased to 150% [95% confidence interval (Cl) 76-256; four studies] for diabetic nephropathy, but decreased to 12% (95% Cl -3 to 28; seven studies) for CHD and 14% (95% Cl -6 to 37; four studies) for myocardial infarction. On the other hand, the pooled odds ratios did not materially change if the meta-analysis was limited to articles published in journals with an impact factor of at least 4. Furthermore, compared with the II control group, the circulating ACE levels (29 studies) were raised 58 and 31% (P< 0.001) in DD and Dl subjects, respectively. In contrast, plasma renin (10 studies), systolic and diastolic blood pressure (46 studies) and body mass index (30 studies) were not associated with the D allele. Conclusion The D allele is not associated with hypertension, but behaves as a marker of atherosclerotic cardiovascular complications and diabetic nephropathy. These associations do not necessarily imply a causal relationship and may have been inflated by publication bias. Nevertheless, their possible therapeutic implications may be subject to further investigation in prospective (intervention) studies.

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones.

Abstract: Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use.

The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.

Abstract: Here we report the sequence of 569,202 base pairs of Saccharomyces cerevisiae chromosome V. Analysis of the sequence revealed a centromere, two telomeres and 271 open reading frames (ORFs) plus 13 tRNAs and four small nuclear RNAs. There are two Ty1 transposable elements, each of which contains an ORF (included in the count of 271). Of the ORFs, 78 (29%) are new, 81 (30%) have potential homologues in the public databases, and 112 (41%) are previously characterized yeast genes.

Erosion, flooding and channel management in Mediterranean environments of southern Europe:

Abstract: Soil erosion by water is one of the most important land degradation processes in Mediterranean environments. This process is strongly linked to problems of flooding and channel management. This art...