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Showing papers by "University of Antwerp published in 1998"


Journal ArticleDOI
TL;DR: The structure-activity relationship of flavonoids as inhibitors of xanthine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthines oxidase, was investigated and showed slightly higher inhibitory activity than flavonols.
Abstract: The structure-activity relationship of flavonoids as inhibitors of xanthine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthine oxidase, was investigated. The hydroxyl groups at C-5 and C-7 and the double bond between C-2 and C-3 were essential for a high inhibitory activity on xanthine oxidase. Flavones showed slightly higher inhibitory activity than flavonols. All flavonoid derivatives except isorhamnetin (30) were less active than the original compounds. For a high superoxide scavenging activity on the other hand, a hydroxyl group at C-3' in ring B and at C-3 were essential. According to their effect on xanthine oxidase and as superoxide scavengers, the flavonoids could be classified into six groups: superoxide scavengers without inhibitory activity on xanthine oxidase (category A), xanthine oxidase inhibitors without any additional superoxide scavenging activity (category B), xanthine oxidase inhibitors with an additional superoxide scavenging activity (category C), xanthine oxidase inhibitors with an additional pro-oxidant effect on the production of superoxide (category D), flavonoids with a marginal effect on xanthine oxidase but with a prooxidant effect on the production of superoxide (category E), and finally, flavonoids with no effect on xanthine oxidase or superoxide (category F).

979 citations


Journal ArticleDOI
01 Apr 1998-Cytokine
TL;DR: It is suggested that changes in the production of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative immunoregulatory cytokine,IL-10 and IL-4, take part in the homeostatic responses to psychological stress and that stress-induced anxiety is related to a T-helper-1-like response.

716 citations


Journal ArticleDOI
TL;DR: The high frequency of carriers of mutations in GJB2 predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population.
Abstract: Background Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle-ear immittance, and recording of otoacoustic emissions. Results Two frame-shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in...

538 citations


Journal ArticleDOI
30 Jul 1998-Nature
TL;DR: In this article, the uniaxial strain and pressure derivatives of T c were analyzed for thin films of copper oxide superconductors, and it was shown that compressive epitaxial strain could in principle generate much larger increases in the critical temperature than obtained by comparable hydrostatic pressures.
Abstract: The discovery1 of high-temperature superconductivity in copper oxides raised the possibility that superconductivity could be achieved at room temperature. But since 1993, when a critical temperature (T c) of 133 K was observed in the HgBa2Ca2Cu3O8+δ (ref. 2), no further progress has been made in raising the critical temperature through material design. It has been shown, however, that the application of hydrostatic pressure can raise T c — up to ∼164 K in the case of HgBa2Ca2Cu3O8+δ (ref. 3). Here we show, by analysing the uniaxial strain and pressure derivatives of T c, that compressive epitaxial strain in thin films of copper oxide superconductors could in principle generate much larger increases in the critical temperature than obtained by comparable hydrostatic pressures. We demonstrate the experimental feasibility of this approach for the compound La1.9Sr0.1CuO4, where we obtain a critical temperature of 49 K in strained single-crystal thin films — roughly double the bulk value of 25 K. Furthermore, the resistive behaviour at low temperatures (but above T c) of the strained samples changes markedly, going from insulating to metallic.

536 citations


Journal ArticleDOI
TL;DR: The finding that carriers of the APOEepsilon4 had no increased risk of dementia suggests an interaction between smoking and the APolipoprotein E (APOE) genotype in the aetiology of Alzheimer's disease.

522 citations


Journal ArticleDOI
TL;DR: It is suggested that APOE is a susceptibility gene for AMD and apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit.
Abstract: Age-related macular degeneration (AMD) is the most common geriatric eye disorder leading to blindness and is characterized by degeneration of the neuroepithelium in the macular area of the eye. Apolipoprotein E (apoE), the major apolipoprotein of the CNS and an important regulator of cholesterol and lipid transport, appears to be associated with neurodegeneration. The apoE gene (APOE) polymorphism is a strong risk factor for various neurodegenerative diseases, and the apoE protein has been demonstrated in disease-associated lesions of these disorders. Hypothesizing that variants of APOE act as a potential risk factor for AMD, we performed a genetic-association study among 88 AMD cases and 901 controls derived from the population-based Rotterdam Study in the Netherlands. The APOE polymorphism showed a significant association with the risk for AMD; the APOE epsilon4 allele was associated with a decreased risk (odds ratio 0.43 [95% confidence interval 0.21-0. 88]), and the epsilon2 allele was associated with a slightly increased risk of AMD (odds ratio 1.5 [95% confidence interval 0.8-2. 82]). To investigate whether apoE is directly involved in the pathogenesis of AMD, we studied apoE immunoreactivity in 15 AMD and 10 control maculae and found that apoE staining was consistently present in the disease-associated deposits in AMD-maculae-that is, drusen and basal laminar deposit. Our results suggest that APOE is a susceptibility gene for AMD.

484 citations


Journal ArticleDOI
TL;DR: Results from the in vitro antiamoebic activity of some Congolese plant extracts used as antidiarrhoeic in traditional medicine indicated that of 45 plant extracts tested, 35 (77.78%) exhibited an antiamoscular activity and 10 (22.22%) were inactive.

481 citations


Journal ArticleDOI
TL;DR: It is concluded that SMCs within human fatty streaks express BAX, which increases the susceptibility of these cells to undergo apoptosis, which could be important in the understanding of the transition of fatty streaks into atherosclerotic plaques, which are characterized by regions of cell death.
Abstract: Background—The transition of a fatty streak into an atherosclerotic plaque is characterized by the appearance of focal and diffuse regions of cell death. We have investigated the distribution of apoptotic cell death and apoptosis-related proteins in early and advanced atherosclerotic lesions. Methods and Results—Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy specimens (n=18). This approach allowed comparison of adaptive intimal thickenings, fatty streaks, and advanced atherosclerotic plaques of the same patient. The fatty streaks differed from adaptive intimal thickenings by the presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both regions were composed mainly of smooth muscle cells (SMCs), and macrophage infiltration was low and not different. Apoptosis, as detected by DNA in situ end labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ nick translation) was not present in these regions. Apoptosis of SMCs and macrophages, ...

428 citations


Journal ArticleDOI
TL;DR: A systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases found polymorphisms were detected in the promoter and the 5'- non-Coding region of PS-1 and in intronic and exonic sequences of PS -- that will be useful in genetic association studies.
Abstract: Two closely related genes, the presenilins ( PS ), located at chromosomes 14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer disease (AD) with onset age below 65 years (presenile AD). We performed a systematic mutation analysis of all coding and 5'-non-coding exons of PS -1 and PS -2 in a population-based epidemiological series of 101 unrelated familial and sporadic presenile AD cases. The familial cases included 10 patients of autosomal dominant AD families sampled for linkage analysis studies. In all patients mutations in the amyloid precursor protein gene ( APP ) had previously been excluded. Four different PS -1 missense mutations were identified in six familial cases, two of which where autosomal dominant cases. Three mutations resulted in onset ages above 55 years, with one segregating in an autosomal dominant family with mean onset age 64 years (range 50-78 years). One PS -2 mutation was identified in a sporadic case with onset age 62 years. Our mutation data provided estimates for PS -1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively. When family history was accounted for mutation frequencies for PS -1 were 9% in familial cases and 18% in autosomal dominant cases. Further, polymorphisms were detected in the promoter and the 5'-non-coding region of PS -1 and in intronic and exonic sequences of PS -2 that will be useful in genetic association studies.

423 citations


Journal ArticleDOI
TL;DR: In contrast to previously proposed methods, ML estimation is demonstrated to be unbiased for high signal-to-noise ratio (SNR) and to yield physical relevant results for low SNR.
Abstract: The problem of parameter estimation from Rician distributed data (e.g., magnitude magnetic resonance images) is addressed. The properties of conventional estimation methods are discussed and compared to maximum-likelihood (ML) estimation which is known to yield optimal results asymptotically. In contrast to previously proposed methods, ML estimation is demonstrated to be unbiased for high signal-to-noise ratio (SNR) and to yield physical relevant results for low SNR.

418 citations


Journal ArticleDOI
TL;DR: Many compounds of plant origin that inhibit different stages in the replication cycle of human immunodeficiency virus (HIV) have been identified and only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS.
Abstract: Many compounds of plant origin have been identified that inhibit different stages in the replication cycle of human immunodeficiency virus (HIV): 1) virus adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids (michellamines), sulphated polysaccharides and polyphenolics, flavonoids, coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus-cell fusion: lectins (mannose- and N-acetylglucosamine-specific) and triterpenes (betulinic acid and analogues); 3) reverse transcription: alkaloids (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins (calanolides and analogues), flavonoids, phloroglucinols, lactones (protolichesterinic acid), tannins, iridoids (fulvoplumierin) and triterpenes; 4) integration: coumarins (3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl derivatives, lignans (arctigenin and analogues) and phenolics (curcumin); 5) translation: single chain ribosome inactivating proteins (SCRIP's); 6) proteolytic cleavage (protease inhibition): saponins (ursolic and maslinic acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation: alkaloids including indolizidines (castanospermine and analogues), piperidines (1-deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8) assembly/release: naphthodianthrones (hypericin and pseudohypericin), photosensitisers (terthiophenes and furoisocoumarins) and phospholipids. The target of action of several anti-HIV substances including alkaloids (O-demethyl-buchenavianine, papaverine), polysaccharides (acemannan), lignans (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B, Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in the proposed scheme. Only a very few of these plant-derived anti-HIV products have been used in a limited number of patients suffering from AIDS viz. glycyrrhizin, papaverine, trichosanthin, castanospermine, N-butyl-1-deoxynojirimicin and acemannan.

Journal ArticleDOI
TL;DR: In this paper, the role of emotional stress in prognosis of patients with myocardial infarction (MI) with a decreased left ventricular ejection fraction (LVEF) was investigated.
Abstract: Background—Patients with myocardial infarction (MI) with a decreased left ventricular ejection fraction (LVEF) have a poor prognosis, but the role of emotional stress in prognosis is not known. We hypothesized that emotional stress in these patients (1) is unrelated to the severity of cardiac disorder, (2) predicts cardiac events, and (3) is a function of basic personality traits. Methods and Results—Eighty-seven patients with MI (age, 41 to 69 years) with an LVEF of ≤50% underwent psychological assessment at baseline. Patients and their families were contacted after 6 to 10 years (mean, 7.9 years); cardiac events were defined as cardiac death or nonfatal MI. Emotional distress was unrelated to the severity of cardiac disorder. At follow-up, 21 patients had experienced a cardiac event (13 fatal events). These events were related to LVEF of ≤30%, poor exercise tolerance, previous MI, anxiety, anger, and depression (all P≤.02). Patients with a distressed personality (type D; ie, the tendency to suppress neg...

Journal ArticleDOI
TL;DR: The findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.
Abstract: The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. a-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse a-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

Journal ArticleDOI
TL;DR: A new method is proposed to estimate the image noise variance for this type of data distribution based on a double image acquisition, thereby exploiting the knowledge of the Rice distribution moments.

Journal ArticleDOI
TL;DR: In intron 7 of this gene, an insertion/deletion mutation is identified that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron.
Abstract: Nonsyndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 loci mapped on the human genome, however, only a limited number of genes implicated in hearing loss have been identified. We previously reported linkage to chromosome 7p15 for autosomal dominant hearing impairment segregating in an extended Dutch family (DFNA5). Here, we report a further refinement of the DFNA5 candidate region and the isolation of a gene from this region that is expressed in the cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation co-segregated with deafness in the family and causes skipping of exon 8, resulting in premature termination of the open reading frame. As no physiological function could be assigned, the gene was designated DFNA5.

Journal ArticleDOI
TL;DR: The results suggest that the inflammatory response in schizophrenia, as indicated by increased serum IL-6 and sIL-6R, may be causally related to lower serum CC16 and that the latter might be a trait marker for schizophrenia.

Journal ArticleDOI
TL;DR: Proteolytic processing of RANTES by CD26/dipeptidyl-peptidase IV may constitute an important regulatory mechanism during anti-inflammatory and antiviral responses.

Journal ArticleDOI
TL;DR: In this article, the 3D nonlinear Ginzburg-landau (GL) equations were solved numerically and nonequilibrium phase transitions between different superconducting states of mesoscopic disks which are thinner than the coherence length and the penetration depth were investigated.
Abstract: Solving numerically the 3D nonlinear Ginzburg-Landau (GL) equations, we study equilibrium and nonequilibrium phase transitions between different superconducting states of mesoscopic disks which are thinner than the coherence length and the penetration depth. We have found a smooth transition from a multivortex superconducting state to a giant vortex state by increasing both the disk thickness and the magnetic field. A vortex phase diagram is obtained which shows, as a function of the magnetic field, a reentrant behavior between the multivortex and the giant vortex state.

Journal ArticleDOI
TL;DR: A single stranded conformational polymorphism (SSCP) assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the Cx26 gene and developed and optimized allele‐specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status within families.
Abstract: Mutations in the Cx26 gene have been shown to cause autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB1 locus on chromosome 13q12. Using direct sequencing, we screened the Cx26 coding region of affected and nonaffected members from seven ARNSHL families either linked to the DFNB1 locus or in which the ARNSHL phenotype cosegregated with markers from chromosome 13q12. Cx26 mutations were found in six of the seven families and included two previously described mutations (W24X and W77X) and two novel Cx26 mutations: a single base pair deletion of nucleotide 35 resulting in a frameshift and a C-to-T substitution at nucleotide 370 resulting in a premature stop codon (Q124X). We have developed and optimized allele-specific PCR primers for each of the four mutations to rapidly determine carrier and noncarrier status within families. We also have developed a single stranded conformational polymorphism (SSCP) assay which covers the entire Cx26 coding region. This assay can be used to screen individuals with nonsyndromic hearing loss for mutations in the CX26 gene.

Journal ArticleDOI
TL;DR: In this paper, the intermediate steps of the phase transition between the metastable monoclinic phase and the stable tetragonal rutile phase have been studied by in situ electron microscopy.
Abstract: The intermediate steps of the phase transition between the metastable monoclinic ${\mathrm{VO}}_{2}(B)$ phase and the stable tetragonal rutile ${\mathrm{VO}}_{2}(R)$ phase have been studied by in situ electron microscopy A crystallographic interpretation based on the static concentration waves theory is proposed: as temperature increases, the long-range order in the complex monoclinic ${\mathrm{VO}}_{2}(B)$ phase is lost and gradually a first intermediate ill crystallized phase with a drastically reduced symmetry is formed as evidenced from the diffraction patterns Next, a new tetragonal phase is generated that corresponds to a state where some of the vanadium atoms are now in a disordered state When annealing inside the microscope, this phase grows out into a superstructure, with coexistence of two possible orientation variants In all these phases the ${\mathrm{VO}}_{6}$ octahedra remain virtually parallel, but for the final transition around 450\ifmmode^\circ\else\textdegree\fi{}C into the rutile stable phase, half of the octahedra have to reorient; the transition therefore has the aspects of a reconstructive one as is evident from the in situ experiment

Journal ArticleDOI
TL;DR: This work has performed further studies of these knockout mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing, and found the ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct.
Abstract: L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.

Journal ArticleDOI
TL;DR: Although both smooth muscle cells and macrophages within the human fatty streaks become susceptible to apoptosis, additional factors are necessary to terminate the cell death pathway, and the TUNEL technique should be combined with additional techniques, such as markers of transcription and morphological criteria.
Abstract: —Several laboratories have demonstrated the presence of apoptotic cell death in atherosclerotic plaques. Apoptosis occurs in at least 2 stages. The final “execution” phase, which includes DNA fragmentation, is brief (≈6 hours) and irreversible and can be detected by the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) technique. The TUNEL technique is only selective (rather than specific) for apoptotic nuclei, because these contain a far greater degree of DNA fragmentation than do nonapoptotic nuclei. Nonapoptotic cell nuclei that show high levels of RNA synthesis and splicing can also be labeled. This could explain the large variation in the reported percentages of TUNEL-positive nuclei in the plaques. Therefore, the TUNEL technique should be combined with additional techniques, such as markers of transcription and morphological criteria. Recent studies indicate that human fatty streaks differ from adaptive intimal thickenings by the presence of cells containing pro-a...

Journal ArticleDOI
TL;DR: In this article, a qualitative research study was conducted to build a specific model of competitive advantage for industrial services, which identifies three core elements in the creation of superior customer value. And three sets of "value drivers" are discussed.
Abstract: This article contributes to the marketing literature by identifying key success factors in industrial service markets. In industrial markets, services are becoming critical for the creation of competitive advantage. However, the marketing of these services has received relatively limited attention in the industrial marketing and services marketing literature. In order to close this gap, the authors undertook a qualitative research study to build a specific model of competitive advantage for industrial services. The model identifies three core elements in the creation of superior customer value. Further, three sets of “value drivers” are discussed. Ideas for further research and recommendations for business practitioners are formulated.

Journal ArticleDOI
TL;DR: There is an activation of the immune-inflammatory response system in primary sleep disorders and depression and the decreased availability of plasma tryptophan may be related to the inflammatory system response.

Journal ArticleDOI
TL;DR: According to the model, the granular layer of the cerebellum is desynchronized when the mossy fiber firing rate is low, and Golgi cells do not only control the strength of parallel fiber activity but also the timing of the individual spikes.
Abstract: Maex, Reinoud and Erik De Schutter. Synchronization of Golgi and granule cell firing in a detailed network model of the cerebellar granule cell layer. J. Neurophysiol. 80: 2521–2537, 1998. The gran...

Journal ArticleDOI
TL;DR: Increased 24‐h UC excretion in patients with PTSD comparable to that in patientsWith major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.
Abstract: There is now firm evidence that major depression is accompanied by increased baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, as assessed by means of 24-h urinary cortisol (UC) excretion. Recently, there were some reports that fibromyalgia and post-traumatic stress disorder (PTSD), two disorders which show a significant amplitude of depressive symptoms, are associated with changes in the baseline activity of the HPA axis, such as low 24-h UC excretion. The aim of the present study was to examine 24-h UC excretion in fibromyalgia and PTSD patients compared to normal controls and patients with major depression. In the three patient groups, severity of depressive symptoms was measured by means of the Hamilton Depression Rating Scale (HDRS) score. Severity of fibromyalgia was measured using a dolorimetrically obtained myalgic score, and severity of PTSD was assessed by means of factor analytical scores computed on the items of the Composite International Diagnostic Interview (CIDI), PTSD Module. Patients with PTSD and major depression had significantly higher 24-h UC excretion than normal controls and fibromyalgia patients. At a threshold value of > or = 240 micrograms/24 h, 80% of PTSD patients and 80% of depressed patients had increased 24 h UC excretion with a specificity of 100%. There were no significant differences in 24-h UC excretion either between fibromyalgia patients and normal controls, or between patients with major depression and PTSD patients. In the three patient groups, no significant correlations were found between 24-h UC excretion and the HDRS score. In fibromyalgia, no significant correlations were found between 24-h UC excretion and the myalgic score. In PTSD, no significant correlations were found between 24-h UC excretion and severity of either depression-avoidance or anxiety-arousal symptoms. In conclusion, this study found increased 24-h UC excretion in patients with PTSD comparable to that in patients with major depression, whereas in fibromyalgia no significant changes in 24-h UC were found.

Journal ArticleDOI
TL;DR: The presenilins (PS‐1 and PS‐2) are 2 members of a novel family of genes encoding integral membrane proteins recently implicated in Alzheimer's disease (AD) pathology, and their high degree of homology predicts similar biological activities.
Abstract: The presenilins (PS-1 and PS-2) are 2 members of a novel family of genes encoding integral membrane proteins recently implicated in Alzheimer's disease (AD) pathology. To date, 43 mutations have been identified in PS-1 and 2 in PS-2 that lead to familial presenile AD (onset before age 65 years). The normal and pathological functions of the PS proteins (ps-1 and ps-2) are unknown, but their high degree of homology predicts similar biological activities. Homologies with ps from other species suggest that they may play a role in intracellular protein sorting and trafficking, in intercellular cell signaling, or in cell death. Since to date only missense mutations and in-frame deletions were identified, it is believed that mutated ps act through either a gain of (dys-)function or a dominant negative effect. In vivo and in vitro studies have linked PS mutations to amyloid deposition, an early pathological event in AD brains. Hum Mutat 11:183–190, 1998. © 1998 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: It is argued here that the multiple internal connective tissue sheets and attachment structures of the well–developed bundles of the vastus muscle become increasingly stretched during preparatory crouching and throughout the extension phase, except for the last 13 ms of the push–off (i.e. when power requirements peak).
Abstract: Bushbabies ( Galago senegalensis ) are renowned for their phenomenal jumping capacity. It was postulated that mechanical power amplification must be involved. Dynamic analysis of the vertical jumps performed by two bushbabies confirms the need for a power amplifier. Inverse dynamics coupled to a geometric musculo–skeletal model were used to elucidate the precise nature of the mechanism powering maximal vertical jumps. Most of the power required for jumping is delivered by the vastus muscle–tendon systems (knee extensor). Comparison with the external joint–powers revealed, however, an important power transport from this extensor (about 65%) to the ankle and the midfoot via the bi–articular calf muscles. Peak power output likely implies elastic recoil of the complex aponeurotic system of the vastus muscle. Patterns of changes in length and tension of the muscle–tendon complex during different phases of the jump were found which provide strong evidence for substantial power amplification (times 15). It is argued here that the multiple internal connective tissue sheets and attachment structures of the well–developed bundles of the vastus muscle become increasingly stretched during preparatory crouching and throughout the extension phase, except for the last 13 ms of the push–off (i.e. when power requirements peak). Then, tension in the knee extensors abruptly falls from its maximum, allowing the necessary fast recoil of the tensed tendon structures to occur.

Journal ArticleDOI
TL;DR: CD26/DPP IV impairs the inflammatory and haematopoietic potency of chemokines but plays a dual role in AIDS.

Journal ArticleDOI
TL;DR: The spectrum of imaging findings in patients with diffuse axonal injuries (DAI) after closed head trauma is reviewed, and technical aspects in MR imaging of these patients are discussed.
Abstract: Even in patients with closed head trauma, brain parenchyma can be severely injured due to disruption of axonal fibers by shearing forces during acceleration, deceleration, and rotation of the head. In this article we review the spectrum of imaging findings in patients with diffuse axonal injuries (DAI) after closed head trauma. Knowledge of the location and imaging characteristics of DAI is important to radiologists for detection and diagnosis. Common locations of DAI include: cerebral hemispheric gray-white matter interface and subcortical white matter, body and splenium of corpus callosum, basal ganglia, dorsolateral aspect of brainstem, and cerebellum. In the acute phase, CT may show punctate hemorrhages. The true extent of brain involvement is better appreciated with MR imaging, because both hemorrhagic and non-hemorrhagic lesions (gliotic scars) can be detected. The MR appearance of DAI lesions depends on several factors, including age of injury, presence of hemorrhage or blood-breakdown products (e. g., hemosiderin), and type of sequence used. Technical aspects in MR imaging of these patients are discussed. Non-hemorrhagic lesions can be detected with fluid attenuated inversion recovery (FLAIR), proton-density-, or T2-weighted images, whereas gradient echo sequences with long TE increase the visibility of old hemorrhagic lesions.