Multiple sclerosis (MS) is believed to be an autoimmune disease of the human central nervous system mediated by autoreactive T cells. Interferon-beta1b (IFN-beta1b) has been shown to be effective in ...reducing disease activity defined by clinical and magnetic resonance imaging (MRI) criteria in relapsing-remitting MS (RRMS). Yet, the exact mechanisms by which these benefits are achieved remain unknown. CD45RA is a marker for naive T lymphocytes and intercellular adhesion molecule-3 (ICAM-3) is expressed on resting lymphocytes.
Forty-eight patients with RRMS, 24 of them treated with recombinant IFN-beta1b and 24 untreated, were enrolled in this prospective study over 18 months. We investigated the percentage of CD45RA+ ICAM-3+ cells within the total lymphocyte subset in the peripheral blood serially every 3 months and in CSF once at baseline. Detailed clinical examination including Expanded Disability Status Scale (EDSS) score was performed every 3 months and cranial MRI scans were assessed every 6 months.
We found a temporary increase in the CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood of both untreated and IFN-beta1b-treated RRMS patients. Moreover, we determined a significant negative correlation (r = -0.5874; P < 0.01) between age as well as the EDSS score (r = -0.3629; P < 0.05) and the percentages of CD45RA+ ICAM-3+ lymphocytes in peripheral blood but a positive correlation between EDSS score and the CD45RA+ ICAM-3+ ratio (r = 0.3913; P < 0.05) in the CSF at baseline.
CD45RA+ ICAM-3+ lymphocyte ratio in peripheral blood might indicate immunosenescence in MS. However, from our data it cannot be finally concluded whether it is also influenced by IFN-beta1b treatment.
Objective: Examine the effectiveness of a robbery and violence prevention program in small businesses in Los Angeles, Methods: Gas/convenience, liquor and grocery stores, bars/restaurants, and motels ...were enrolled between 1997 and 2000. Intervention businesses (n = 305) were provided training, program implementation matenals, and recommendations for a comprehensive security program. Contro businesses (n = 96) received neither training nor program materials. Results: Rate ratios comparing intervention to control businesses were 0.90 for violent crime (95% confidence limits CL = 0.53, 1.53) and 0.81 for robbery (95% CL = 0.38, 1.73). The reduction in violent crime was concentrated in high-compliance intervention businesses (risk ratio = 0.74, 95% CL = 0.40, 1.36). Low-compliance intervention businesses had practically the same postintervention crime as the contro businesses. Conclusions: Our results suggest that the workplace violen intervention may reduce violent crime among high-risk businesses, especially those with high program compliance.
Although medulloblastoma (MB) represents the most frequent malignant brain tumour in children, the molecular pathogenesis of this tumour is still poorly understood. Microsatellite and RFLP studies ...have revealed allelic losses on the short arm of chromosome 17 in the region 17p13 in approximately 50% of MBs. A candidate for this putative MB suppressor on chromosome 17p13.3 is the recently cloned LIS-1 gene which codes for a regulatory subunit of the intracellular form of the platelet activating factor (PAF) acetylhydrolase. PAF is involved in signal transduction pathways during cerebral development and in the process of neuronal cell migration and differentiation. In this study, 42 medulloblastomas including seven tumour cell lines and 35 primary tumours were analysed for LIS-1 mRNA expression by RT-PCR and Northern blot analysis. Twenty-four paired blood and MB DNA samples were examined by PCR analysis with a panel of microsatellites located on chromosome 17p to detect loss of heterozygosity (LOH). Finally, the single-strand conformation polymorphism (SSCP) technique and DNA sequencing were employed to detect mutations or small deletions in the coding region of the LIS-1 gene. Of 24 MBs, 13 exhibited loss of heterozygosity on chromosome 17p13.3 for at least one of the microsatellite markers. LIS-1 mRNA expression was detected in all MB tumours and MB cell lines. None of the tumours showed a somatic mutation in the LIS-1 coding region. A novel polymorphism in the 3'UTR of LIS-1 was found in MB patients, but also in healthy control persons. These data indicate that the LIS-1 gene located at 17p13.3 is not involved in the molecular pathogenesis of MBs.
Recently, a data-driven model-free control design method has been proposed in Hjalmarsson et al. (Proceedings of the Conference on Decision and Control, Orlando, FL, 1994, pp. 1735–1740; IEEE Control ...Systems Mag. 18 (1998) 26) for linear systems. It is based on the minimization of a control criterion with respect to the controller parameters using an iterative gradient technique. In this paper, we extend this method to the case where both the plant and the controller can be nonlinear. It is shown that an estimate of the gradient of the control criterion can be constructed using only signal-based information obtained from closed-loop experiments. The obtained estimate contains a bias which depends on the local nonlinearity of the noise description of the closed-loop system which can be expected to be small in many practical situations. As a side effect the linear model-free control design method is reobtained in a new way.
Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism spectrum disorders (ASD). ASD were reported predominantly in congenital and early childhood ...forms of DM1. We describe dizygotic twin boys with ASD who were referred for routine laboratory genetic testing and in whom karyotyping,
gene testing, and single nucleotide polymorphism array analysis yielded negative results. The father of the boys was later diagnosed with suspected DM1, and testing revealed characteristic
gene expansions in his genome as well as in the genomes of both twins and their elder brother, who also suffered from ASD. In accord with previous reports on childhood forms of DM1, our patients showed prominent neuropsychiatric phenotypes characterized especially by hypotonia, developmental and language delay, emotional and affective lability, lowered adaptability, and social withdrawal. The experience with this family and multiple literature reports of ASD in DM1 on the one side but the lack of literature data on the frequency of
gene expansions in ASD patients on the other side prompted us to screen the
gene in a sample of 330 patients with ASD who were first seen by a geneticist before they were 10 years of age, before the muscular weakness, which may signal DM1, usually becomes obvious. The absence of any
gene expansions in this cohort indicates that targeted
gene testing can be recommended only in ASD patients with specific symptoms or family history suggestive of DM1.
We determined the molecular basis of cystathionine beta-synthase (CBS) deficiency in three siblings with pyridoxine responsive homocystinuria using a significantly improved mutation screening method ...in bacteria. The phenotypic expression of the siblings differed even though their CBS genotypes were identical. The paternal allele contained a linked pair of mutations, C233G and G306C, corresponding to P78R and K102N in the polypeptide chain. Together, these inactivated the enzyme; however, expressed separately, they reduced activity by about one half. The single maternal mutation G715A (E239K) effectively abolished CBS activity. Subunits of CBS were absent from patient fibroblast extracts; however, E. coli, transformed with plasmids containing patient CBS cDNA, expressed the subunits, although in reduced amounts. The mother, an obligate heterozygote, was free from all signs of homocystinuria; nonetheless, extracts of her fibroblasts were devoid of CBS protein and activity. We conclude that fibroblast levels of CBS are only partially effective as prognosticators of disease severity and that it is important to test the in vivo response to vitamin B6 in all cases of homocystinuria, including those in which the mutations lead to the absence of the enzyme in cultured fibroblasts.
The use of extrusions for stiff and lightweight design is widespread. Whilst many applications can be realised with straight extrusions, some applications demand the use of bent extrusions. By ...introducing the use of bent extrusions into automotive applications, the demands for higher accuracy as well as highly flexible methods were increased. This review gives a systematic overview about the existing processes for the bending of extrusions in small scale (e.g. rapid prototyping) and large scale production (e.g. automotive mass production). The methods are systematised in a 2×3 matrix. There are two main groups of processes, which are kinematic shaping, based on forming by defined relative motion of the tool and workpiece, and forming with shape-defining tools, i.e. forming by adapting the raw part to a shaping tool. With respect to the moments in action, it can be differentiated between bending without a moment, bending with constant moment, and bending with position-dependent moment. Further, some considerations are given as to how to develop the process design for the bending operation. In addition, some of the important features of working accuracy in bending extrusions are reviewed. This includes two questions: the accuracy of the curvature; and the deviations in the cross section. Methods of open- and closed-loop control based on process modelling for an increase of accuracy are shown as well as the practical methods to avoid cross section deformation.
Interaction of rat and human cystathionine-β-synthase (CBS) with various potential ligands has been studied by visible and EPR spectroscopy in order to explore the coordination chemistry of this ...atypical hemeprotein. Ferric CBS did not react with any classical hemeprotein ligands, such as various imidazole and pyridine derivatives, N−3 and isonitriles RNC. Ferrous CBS also failed to bind these nitrogenous ligands or nitrosoalkanes. However, it reacts with various isonitriles RNC, leading to complexes characterized by a Soret peak at 433 ± 2 nm. Binding of isonitriles to ferrous CBS is a relatively slow process; its rate markedly depends on the nature of R. It thus seems that the only exogenous ligands able to bind CBS iron are carbon-centered, very strong heme–Fe(II) ligands such as CNR, CO, and CN−, presumably after dissociation of the CBS–iron(II)–cysteinate bond. Isonitriles appear as interesting tools for further studies on the topology of CBS active site.
A glass ceramic system based on a glass of nominal composition (mol%) 32.4SiO
2–8.1Al
2O
3–31.4CdF
2–5.4ZnF
2–4.3YF
3–18.4PbF
2 (TGC) doped with 500 ppmw of PrF
3 has been prepared and studied to ...explore the possibility of using it for optical fibre amplifiers operating at 1.3 μm. A comparative analysis of two samples having the same nominal composition, but obtained in different conditions, showed that one sample was completely amorphous, while the other one contained crystals of the phase Pb
x
Cd
1−
x
F
2. Crystals of the same phase were found in the amorphous sample after isochronal and isothermal treatments, obtaining a glass ceramic system transparent in the visible range. The coarsening of the crystals investigated by DSC, TEM, XRD decreased on annealing while the photoluminescence intensity increased, indicating a change in the surrounding of Pr
3+ ions during the controlled ceramming process. Finally, based on the study of the rheological properties of the glass ceramic system we suggest that the temperature interval suitable for fibre drawing is between 572°C and 614°C.
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