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Biomedical subjects

C Reich

Publications and source records attributed to C Reich.

At least 19 recordsLinked to original sources

Patient information on cognitive symptoms in multiple sclerosis - acceptability in relation to disease duration.

OBJECTIVE: Recently, regular cognitive screening assessments have been advised in multiple sclerosis (MS). No studies have been carried out yet on the acceptability of information on cognitive deficits among MS patients. MATERIALS AND METHODS: Translation of an information booklet developed by a working group of European MS Rehabilitation Centers. Distribution of the booklet among 133 MS patients of two rehabilitation units and one outpatient clinic together with a one-page questionnaire. RESULTS: The booklet was highly understandable and rated to give moderate new information. Overall, the brochure was perceived as encouraging but significantly less so (P = 0.014) in recently diagnosed patients. Patients with subjectively perceived deficits considered the brochure to be significantly more relevant (P = 0.002). CONCLUSION: Information on cognitive deficits does not increase fears even in recently diagnosed MS patients. Patients with perceived deficits found the information more relevant than others and also less familiar. Thus, it seems appropriate to offer information about cognitive impairments to MS patients.

Adult↗

Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?

BACKGROUND: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. METHODS: We compared whole blood stimulatory capacity for pro- (TNFalpha, IFNgamma) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). RESULTS: Proinflammatory cytokines were significantly higher (TNFalpha: 478.9 v 228.2 pg/ml, p = 0.01; IFNgamma: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFalpha values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. CONCLUSION: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.

Adrenocorticotropic Hormone↗

Upward renormalization of fluctuations in CsMnBr3 with increasing temperature.

The temperature dependence of the spin-wave gap in the triangular antiferromagnet CsMnBr3 was studied above the three-dimensional ordering temperature T(N)=8.3 K along the main symmetry directions using inelastic neutron scattering. We find at T(N) two gapped dispersive modes, whose energy increases with temperature. Moreover, the width of the spin-wave band along the [110] direction increases also. In a second session, polarization analysis was applied in order to extract explicitly the components with in-plane and out-of-plane character. The results show that both gapped modes (with axial and radial symmetry) renormalize upwards with rising temperature. We show that this behavior is not compatible with spin-wave theory. In addition, we find a new magnetic anomaly in the paramagnetic phase.

Journal Article↗

Mev X rays and photoneutrons from femtosecond laser-produced plasmas.

We demonstrate a novel method to monitor the total angular distribution of the spectrum of hard x-ray emission from a plasma generated with femtosecond laser pulses with an intensity of 5 x 10(18) W/cm2 on a solid target. Measured and calculated angular distributions of x rays show a pronounced anisotropy for MeV photon energies. We complemented the spectral information by demonstrating a (gamma,n) nuclear reaction with a tabletop laser system.

Journal Article↗

Secretion of whey acidic protein and cystatin is down regulated at mid-lactation in the red kangaroo (Macropus rufus).

Milk collected from the red kangaroo (Macropus rufus) between day 100 and 260 of lactation showed major changes in milk composition at around day 200 of lactation, the time at which the pouch young begins to temporarily exit the pouch and eat herbage. The carbohydrate content of milk declined abruptly at this time and although there was only a small increase in total protein content, SDS PAGE analysis of milk revealed asynchrony in the secretory pattern of individual proteins. The levels of alpha-lactalbumin, beta-lactoglobulin, serum albumin and transferrin remain unchanged during lactation. In contrast, the protease inhibitor cystatin, and the putative protease inhibitor whey acidic protein (WAP) first appeared in milk at elevated concentrations after approximately 150 days of lactation and then ceased to be secreted at approximately 200 days. In addition, a major whey protein, late lactation protein, was first detected in milk around the time whey acidic protein and cystatin cease to be secreted and was present at least until day 260 of lactation. The co-ordinated, but asynchronous secretion of putative protease inhibitors in milk may have several roles during lactation including tissue remodelling in the mammary gland and protecting specific proteins in milk required for physiological development of the dependent young.

Amino Acid Sequence↗

Host response to infection: the role of CpG DNA in induction of cyclooxygenase 2 and nitric oxide synthase 2 in murine macrophages.

Depending on sequence, bacterial and synthetic DNAs can activate the host immune system and influence the host response to infection. The purpose of this study was to determine the abilities of various phosphorothioate oligonucleotides with cytosine-guanosine-containing motifs (CpG DNA) to activate macrophages to produce nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and to induce expression of NO synthase 2 (NOS2) and cyclooxygenase 2 (COX2). As little as 0.3 microg of CpG DNA/ml increased NO and PGE(2) production in a dose- and time-dependent fashion in cells of the mouse macrophage cell line J774. NO and PGE(2) production was noted by 4 to 8 h after initiation of cultures with the CpG DNA, with the kinetics of NO production induced by CpG DNA being comparable to that induced by a combination of lipopolysaccharide and gamma interferon. CpG DNA-treated J774 cells showed enhanced expression of NOS2 and COX2 proteins as determined by immunoblotting, with the relative potencies of the CpG DNAs generally corresponding to those noted for the induction of NO and PGE(2) production as well as to those noted for the induction of interleukin-6 (IL-6), IL-12, and tumor necrosis factor. Extracts from CpG DNA-treated cells converted L-arginine to L-citrulline, but the NOS inhibitor N(G)-monomethyl-L-arginine (NMMA) inhibited this reaction. The COX2-specific inhibitor NS398 inhibited CpG DNA-induced PGE(2) production and inhibited NO production to various degrees. The NOS inhibitors NMMA, 1400W, and N-iminoethyl-L-lysine effectively blocked NO production and increased the production of PGE(2) in a dose-dependent fashion. Thus, analogues of microbial DNA (i.e., CpG DNA) activate mouse macrophage lineage cells for the expression of NOS2 and COX2, with the production of NO and that of PGE(2) occurring in an interdependent manner.

Adjuvants, Immunologic↗

Yield optimization and time structure of femtosecond laser plasma kalpha sources

The generation of femtosecond Kalpha x rays from laser-irradiated plasmas is studied with a view to optimizing photon number and pulse duration. Using analytical and numerical models of hot electron generation and subsequent transport in a range of materials, it is shown that an optimum laser intensity I(opt) = 7x10(9)Z4.4 exists for maximum Kalpha yield. Furthermore, it is demonstrated that bulk targets are unsuitable for generating sub-ps x-ray pulses: instead, design criteria are proposed for achieving Kalpha pulse durations </=100 fs using foils of approximately 2 &mgr;m thickness.

Journal Article↗

Automated genome sequence analysis and annotation.

MOTIVATION: Large-scale genome projects generate a rapidly increasing number of sequences, most of them biochemically uncharacterized. Research in bioinformatics contributes to the development of methods for the computational characterization of these sequences. However, the installation and application of these methods require experience and are time consuming. RESULTS: We present here an automatic system for preliminary functional annotation of protein sequences that has been applied to the analysis of sets of sequences from complete genomes, both to refine overall performance and to make new discoveries comparable to those made by human experts. The GeneQuiz system includes a Web-based browser that allows examination of the evidence leading to an automatic annotation and offers additional information, views of the results, and links to biological databases that complement the automatic analysis. System structure and operating principles concerning the use of multiple sequence databases, underlying sequence analysis tools, lexical analyses of database annotations and decision criteria for functional assignments are detailed. The system makes automatic quality assessments of results based on prior experience with the underlying sequence analysis tools; overall error rates in functional assignment are estimated at 2.5-5% for cases annotated with highest reliability ('clear' cases). Sources of over-interpretation of results are discussed with proposals for improvement. A conservative definition for reporting 'new findings' that takes account of database maturity is presented along with examples of possible kinds of discoveries (new function, family and superfamily) made by the system. System performance in relation to sequence database coverage, database dynamics and database search methods is analysed, demonstrating the inherent advantages of an integrated automatic approach using multiple databases and search methods applied in an objective and repeatable manner. AVAILABILITY: The GeneQuiz system is publicly available for analysis of protein sequences through a Web server at http://www.sander.ebi.ac. uk/gqsrv/submit

Amino Acid Sequence↗

Attachment of gelatin films to tissue using argon beam coagulator.

Cross-linked gelatin films were bonded to heart muscle and to lung pleura and parenchyma using the electrical discharge of an argon beam radiofrequency coagulator. The bonds were stable in warm saline buffer for minutes to hours. Bonding was thought to partly occur through a mechanical interlock of film and tissue elements. The interdigitation of tissue and film arose during exposure to the argon beam, which denatured protein constituents of both, and created a fluidized state that rapidly coalesced.

Animals↗

CD26 (dipeptidyl peptidase i.v.) on human T lymphocytes does not mediate adhesion of these cells to endothelial cells or fibroblasts.

We have examined the role of CD26 (dipeptidyl peptidase IV) in the adhesion of resting and activated T lymphocytes to endothelial cells and fibroblasts. For this purpose, we ran a short-time adhesion assay under different strategies: Adhesion of T lymphocytes was determined in the presence of different anti-CD26 monoclonal antibodies, or in the presence of synthetic inhibitors of the enzymatic function of CD26. In addition, the expression of CD26 on T lymphocytes, which were adherent to endothelial cells or fibroblasts, was performed by flow cytometric analysis. We found that the anti-CD26 monoclonal antibodies tested here were not able to inhibit T cell adhesion to monolayers of endothelial cells or fibroblasts. Secondly, synthetic inhibitors of the enzymatic function of CD26 had no effect on the adhesion of T lymphocytes to endothelial cells or fibroblasts. Furthermore, CD26-positive T cells were not accumulated in the adherent population. These results suggest that CD26 on T lymphocytes plays no role in T cell adhesion to endothelial cells or fibroblasts.

Dipeptidyl Peptidase 4↗

Neuropeptide Y in the infundibular nucleus and hypophysis of great apes.

We studied the distribution of neuropeptide Y (NPY) immunoreactivity in the infundibular nucleus and the hypophysis of the chimpanzee, gorilla, and orangutan. Using antibodies developed in rabbit against synthetic porcine NPY, we found numerous NPY-immunoreactive neuronal somata in the infundibular nucleus; this nucleus was also filled with short NPY-positive processes and an abundance of punctate structures that could be indicative of synaptic terminals. Numerous varicose NPY-positive fibers were concentrated in the upper infundibular stem in association with capillary loops of the portal vasculature and with the long portal vessels. Bundles of long varicose fibers ran down the infundibular stem, some appearing to terminate in the lower stem in the vicinity of short portal vessels. The bulbous infundibular process contained only sparsely distributed fibers; they were mostly concentrated near vessels at the border between the infundibular process and the anterior pituitary gland, where the fibers often terminated in a spray-like fashion near blood vessels. No NPY immunoreactivity was seen in the anterior pituitary gland. These results provide anatomical evidence for the release of NPY into the portal vasculature of great apes.

Animals↗

Small-diameter corneal inlay in presbyopic or pseudophakic patients.

We report the results of using the small-diameter corneal inlay to create a bifocal cornea. The inlay was implanted in five eyes in January 1993. At 12 months postoperatively, uncorrected near vision had improved from J4 to better than J2 in four of the five. The results indicate that the corneal inlay improves near vision and is compatible within the cornea.

Adult↗

Antibody-induced modulation of CD26 surface expression.

The ability of different anti-CD26 monoclonal antibodies to modulate the expression of CD26 on human T lymphocytes was investigated. By means of a new non-radioactive method using fluorescein isothiocyanate (FITC)-labelled and unlabelled anti-CD26 monoclonal antibodies and flow cytometry, we measured the internalization and re-expression of CD26 on freshly isolated resting human T lymphocytes. The modulation of CD26 surface expression takes place in primarily CD26+ as well as in CD26- T lymphocytes, indicating the presence of an intracellular CD26 pool. In fact, with two different anti-CD26 monoclonal antibodies (Ta1 and M5) intracellular CD26 was detected out of which newly expressed CD26 might have originated. This intracellular CD26 pool appears to be maintained by continuous translation of CD26 mRNA.

Antibodies, Monoclonal↗

Genetic and biochemical analysis of the fission yeast ribonucleoprotein particle containing a homolog of Srp54p.

Mammalian signal recognition particle (SRP), a complex of six polypeptides and one 7SL RNA molecule, is required for targeting nascent presecretory proteins to the endoplasmic reticulum (ER). Earlier work identified a Schizosaccharomyces pombe homolog of human SRP RNA and showed that it is a component of a particle similar in size and biochemical properties to mammalian SRP. The recent cloning of the gene encoding a fission yeast protein homologous to Srp54p has made possible further characterization of the subunit structure, subcellular distribution, and assembly of fission yeast SRP. S. pombe SRP RNA and Srp54p co-sediment on a sucrose velocity gradient and coimmunoprecipitate, indicating that they reside in the same complex. In vitro assays demonstrate that fission yeast Srp54p binds under stringent conditions to E. coli SRP RNA, which consists essentially of domain IV, but not to the full-length cognate RNA nor to an RNA in which domain III has been deleted in an effort to mirror the structure of bacterial homologs. Moreover, the association of S. pombe Srp54p with SRP RNA in vivo is disrupted by conditional mutations not only in domain IV, which contains its binding site, but in domains I and III, suggesting that the particle may assemble cooperatively. The growth defects conferred by mutations throughout SRP RNA can be suppressed by overexpression of Srp54p, and the degree to which growth is restored correlates inversely with the severity of the reduction in protein binding. Conditional mutations in SRP RNA also reduce its sedimentation with the ribosome/membrane pellet during cell fractionation. Finally, immunoprecipitation under native conditions of an SRP-enriched fraction from [35S]-labeled fission yeast cells suggests that five additional polypeptides are complexed with Srp54p; each of these proteins is similar in size to a constituent of mammalian SRP, implying that the subunit structure of this ribonucleoprotein is conserved over vast evolutionary distances.

Base Sequence↗

Microglial tyrosine phosphorylation systems in normal and degenerating brain.

Phosphotyrosine and protein tyrosine phosphatase antibodies have been used to assess the distribution and potential functions of tyrosine phosphorylation systems in normal brain and cell cultures, as well as in a model of neural degeneration. Western blot and immunohistochemical analysis showed that a panel of antiphosphotyrosine antibodies recognizing different tyrosine phosphorylated substrates all selectively labeled ramified microglia in sections of brain tissue. This significantly extends our previous observation (GLIA 2:412-419, 1989) that a single, limited, phosphotyrosine antibody served as a histological marker for microglia. The present results show that tyrosine phosphorylation of a variety of substrates is quantitatively enriched in microglia compared to other neural cell types. We also show that the protein tyrosine phosphatase, CD45, is constitutively expressed by ramified microglia in vivo and by ameboid microglia in vitro. Thus, the major enzymes constituting tyrosine phosphorylation systems are present in normal microglia. Neuronal degeneration in the trigeminal nucleus, caused by introduction of the neurotoxic lectin, ricin, into the peripheral nerve is accompanied by a robust upregulation of phosphotyrosine signal in ramified microglial adjacent to the nucleus and in ameboid microglia in the degenerating nucleus. The presence of phosphotyrosine in ramified microglia is consistent with a role for tyrosine phosphorylation systems in the activation of microglia and in the signaling events accompanying conversion of resting microglia to the ameboid form.

Animals↗

Proline-directed kinase systems in Alzheimer's disease pathology.

Immunohistochemical analysis was used to assess the distribution of the proline-directed kinase, cdc2, in Alzheimer's disease (AD) pathology. A robust signal was most prominent in the neurofibrillary tangle (NFT) of affected neurons that also contained abnormally phosphorylated tau protein. Biochemical analysis identified a pool of cdc2 in bovine brain microtubules that contain normal tau. These results strongly support the hypothesis that cdc2 is involved in the abnormal phosphorylation of tau in AD pathology and they raise important issues regarding regulation of tau phosphorylation in normal and diseased neurons.

Aged↗

Stimulation of in vitro proliferation of murine lymphocytes by synthetic oligodeoxynucleotides.

To elucidate the properties of mitogenic nucleic acids, the ability of oligodeoxynucleotides to stimulate the in vitro proliferation of murine lymphocytes was investigated. The compounds tested were a series of oligodeoxynucleotides, synthesized with either phosphodiester or phosphorothioate chemistry and containing (dG) and (dC) alone or together. Among oligodeoxynucleotides tested, phosphorothioates were more active than phosphodiesters and stimulated thymidine incorporation under the same conditions as mitogenic non-mammalian DNA. Mitogenesis was unaffected by depletion of T cells, suggesting B cells as the predominant cell type stimulated. These results indicate that mitogenic nucleic acids need not have an extended polymeric structure and raise the possibility that antisense compounds have immunologic activity, at least in animal models.

Animals↗