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PubMed1999

Detecting unitary events without discretization of time.

In earlier studies we developed the 'Unitary Events' analysis (Grün S. Unitary Joint-Events in Multiple-Neuron Spiking Activity: Detection, Significance and Interpretation. Reihe Physik, Band 60. Thun, Frankfurt/Main: Verlag Harri Deutsch, 1996.) to detect the presence of conspicuous spike coincidences in multiple single unit recordings and to evaluate their statistical significance. The method enabled us to study the relation between spike synchronization and behavioral events (Riehle A, Grün S, Diesmann M, Aertsen A. Spike synchronization and rate modulation differentially involved in motor cortical function. Science 1997;278:1950-1953.). There is recent experimental evidence that the timing accuracy of coincident spiking events, which might be relevant for higher brain function, may be in the range of 1-5 ms. To detect coincidences on that time scale, we sectioned the observation interval into short disjunct time slices ('bins'). Unitary Events analysis of this discretized process demonstrated that coincident events can indeed be reliably detected. However, the method looses sensitivity for higher temporal jitter of the events constituting the coincidences (Grün S. Unitary Joint-Events in Multiple-Neuron Spiking Activity: Detection, Significance and Interpretation. Reihe Physik, Band 60. Thun, Frankfurt/Main: Verlag Harri Deutsch, 1996.). Here we present a new approach, the 'multiple shift' method (MS), which overcomes the need for binning and treats the data in their (original) high time resolution (typically 1 ms, or better). Technically, coincidences are detected by shifting the spike trains against each other over the range of allowed coincidence width and integrating the number of exact coincidences (on the time resolution of the data) over all shifts. We found that the new method enhances the sensitivity for coincidences with temporal jitter. Both methods are outlined and compared on the basis of their analytical description and their application on simulated data. The performance on experimental data is illustrated.

Action Potentials↗
PubMed1996

Induction of hypoploidy and cell cycle delay by acrylamide in somatic and germinal cells of male mice.

Monomeric acrylamide was tested for its potential to induce aneuploidy in spermatocytes and bone marrow cells of mice. For this purpose, chromosomes from metaphase spreads were counted semi-automatically. In both test systems, cell proliferation was monitored, determining the meiotic index of spermatocytes and the average generation time of bone marrow cells after BrdU incorporation, respectively. No indications could be seen for different sensitivity of somatic and germinal cells towards acrylamide. With a dose of 120 mg/kg, the chemical caused cell cycle delay in both germ line and somatic cells. There was diverging response with respect to the balance of hypo- and hyperploidy. While the percentage of chromosome loss was significantly elevated in both test systems, acrylamide treatment did not increase the frequency of hyperploid cells. Interpreting these results on the basis of conventional test protocols, acrylamide should not be considered as an aneugen. The conservative approach, however, may be inadequate for the detection of aneugenic mechanisms different from non-disjunction.

Acrylamide↗
PubMed1997

The advantages and disadvantages of the cytokinesis-block micronucleus method.

There is current interest in adopting the micronucleus test instead of metaphase analysis of chromosomes to assess the in vitro genotoxic potential of chemical and physical agents. In this paper, the advantages and disadvantages of the cytokinesis-block micronucleus technique relative to metaphase analysis of chromosomes and the conventional micronucleus technique that does not distinguish between dividing and non-dividing cells are discussed. Furthermore, additional features, such as the measurement of non-disjunction, excision-repairable DNA lesions and HPRT variants and possibilities for further improving the application of the cytokinesis-block method are proposed.

Animals↗
PubMed1999

Emotional responding in deficit and non-deficit schizophrenia.

Although emotional dysfunction is presumed to be a central part of the deficit syndrome in schizophrenia, it has not yet been empirically investigated in deficit and non-deficit patients. Emotional responding was examined in 19 male deficit patients, 22 non-deficit patients, and 20 non-patient controls. Patients participated in a semi-structured clinical interview that included questions from the Schedule for the Deficit Syndrome (SDS) and the Brief Psychiatric Rating Scale (BPRS), and then were then categorized into deficit and non-deficit groups. In addition, all participants viewed emotional films while their facial expressions were videotaped and then completed self-reports of emotional experience following each film. As predicted, deficit patients were less expressive than non-deficit patients and controls across the films. Contrary to prediction, deficit patients did not report experiencing less emotion to the films than non-deficit patients or controls. Thus, a disjunction in emotional responding appeared to characterize deficit patients, who were less expressive than controls but did not report less emotional experience. Alternative explanations for the findings are considered as are directions for future research.

Adult↗
PubMed1997

Ph-positive CML in blastic phase with monosomy 7 in a Down syndrome patient. Monitoring by interphase cytogenetics and demonstration of maternal allelic loss.

We report a case of Ph-positive chronic myelocytic leukemia in blastic phase in an 11-year-old boy with Down syndrome. Monosomy 7 was the only additional chromosomal anomaly in the blastic clone. Fluorescence in situ hybridization analysis on interphase nuclei with a centromeric probe specific to chromosome 7 proved to be efficient in disease monitoring, and showed, together with the results of chromosome analysis on metaphases, that B-lymphocytes at the origin of an EBV-established line were not part of the leukemic clone. The study of DNA polymorphisms showed that the origin of the constitutional trisomy 21 was a maternal anaphase I nondisjunction, that the chromosome 7 lost in the blastic marrow clone was the maternal one, and led us to postulate that the mother's chromosomes are prone to impairment of normal disjunction. The study of allelic losses of chromosome 7 loci proved to be a further possibility for disease monitoring.

Adult↗
PubMedDate not supplied

Promise and problems in relating cellular senescence in vitro to aging in vivo.

According to the 'Hayflick limit', human fetal fibroblasts have a uniform, limited replicative lifespan of about 50 population doublings in cell culture. This concept was extrapolated to diverse cells in the body. It seemed to decrease with the age of the cell donor and, as a form of cell senescence, was thought to underlie the aging process. More discriminating analysis, however, showed that the fibroblasts decayed in a stochastic manner from the time of their explantation, at a rate that increased with the number of population doublings in culture. There was no consistent relation to the age of the donor. Despite the contradictory evidence, the original version of the Hayflick limit retained its general acceptance. Cell senescence was attributed to the absence of telomerase in the fibroblasts, which resulted in shortening of telomeres at each division until they fell below a critical length needed for further division. However, it is well established that stem cells in renewing tissues undergo many more than 50 divisions in a lifetime, without apparent senescence. Contrary to early findings of no telomerase in most tissues, their stem cells retain telomerase and presumably telomere length despite many divisions in vivo. Massive accumulation of lipofuscin granules occurs under stress in long term crowded cultures, but the granules dissipate on subculture or neoplastic transformation. The overall results indicate a critical disjunction between cell senescence in vitro and aging in vivo. By contrast, cell culture has been useful in showing a need for telomere capping in maintaining cell stability and viability. It may also provide information about the biochemical mechanism of lipofuscin production.

Journal Article↗
PubMed2003

The influence of social norms on hunger ratings and eating.

Restrained and unrestrained eaters were exposed to fictitious hunger reports (high-hunger, low-hunger) of ostensible prior participants in the experiment. In the control condition, participants were not exposed to prior-participant reports. Participants rated their own hunger and then consumed cookies during a 'taste-test.' The fictitious hunger ratings of prior participants exerted a strong effect (p<0.001) on actual participants' hunger ratings; however, food intake was not affected by the fictitious hunger ratings (or by the actual participants' hunger ratings). We discuss the disjunction between hunger ratings and eating, specifically whether (a) hunger reports were fabricated in response to social pressure or (b) eating is controlled by factors other than hunger.

Adult↗
PubMed2003

From guidelines to clinical practice: the impact of hospital and geographical characteristics on temporal trends in the management of acute coronary syndromes. The Global Registry of Acute Coronary Events (GRACE).

AIMS: The extent to which hospital and geographic characteristics influence the time course of uptake of evidence from key clinical trials and practice guidelines is unknown. The gap between evidence and practice is well recognized but the factors influencing this disjunction, and the extent to which such factors are modifiable, remain uncertain. METHODS AND RESULTS: Using chronological data from the GRACE registry (n=12666, July 1999 to December 2001), we test the hypothesis that hospital and geographic characteristics influence the time course of uptake of evidence-based guideline recommendations for acute coronary syndromes (ACS) with and without ST elevation. Certain therapies were widely adopted in both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients (aspirin >94% of all patients; beta-blockers 85-95%) and changed only modestly over time. Significant increases in the use of low-molecular-weight heparins and glycoprotein IIb/IIIa inhibitors occurred in STEMI and NSTEMI patients in advance of published practice guidelines (September/November 2000) with marked geographical differences. The highest use of LMWH was in Europe in NSTEMI (86.8%) and the lowest in the USA (24.0%). Contrasting geographical variations were seen in the use of percutaneous coronary intervention (PCI) in NSTEMI: 39.5% USA, 34.6% Europe, 33.5% Argentina/Brazil, 25.0% Australia/New Zealand/Canada (July-December 2001). Theuse of PCI was more than five times greater in hospitals with an on-site catheterization laboratory compared to centres without these facilities, and geographic differences remained after correction for available facilities. CONCLUSIONS: Hospital and geographical factors appear to have a marked influence on the uptake of evidence-based therapies in ACS management. The presentation and publication of major international guidelines was not associated with a measurable change in the temporal pattern of practice. In contrast, antithrombotic and interventional therapies changed markedly over time and were profoundly influenced by hospital and geographic characteristics.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

[A diagnosis to consider: insufficiency fracture of the sacrum].

The authors report a case of insufficiency fracture of the sacrum in an 81-year old woman. The fracture was related to disjunction of the pubic symphysis consecutive to curettage of the pubic bones for septic osteitis developed after vulvectomy for cancer. The diagnosis was suspected on the results of bone scintigraphy and was confirmed by computerized tomography with frontal sections and contrast inversion, showing the characteristic H-shaped fracture.

Aged↗
PubMed1997

Cu accumulation in the earthworm Dendrobaena veneta in a heavy metal (Cu, Pb, Zn) contaminated site compared to Cu accumulation in laboratory experiments.

Earthworms (Dendrobaena veneta) were exposed to heavy metal contaminated soil from a field site under both laboratory and field conditions. In the laboratory study, D. veneta were analysed for Cu after 2 weeks' exposure. The tissue Cu concentration (Cu(W)) increased proportionally with the total extractable soil Cu content (Cu(T)) in soils that contained less than 150 mg Cu kg(-1). In D. veneta exposed to soils containing more than Cu(T) = 150 mg kg(-1), however, we observed no further increase in Cu(W). In a 64-m(2) field plot at a contaminated site, 81 soil samples were taken and analysed for Cu, Pb, Zn and pH. In June 1994, 1000 D. veneta were homogeneously distributed in the plot and sampled after 1, 2 and 5 weeks to analyse for Cu. Additionally, 2000 D. veneta were introduced in September 1994 and sampled after 1, 2 and 4 weeks. At locations where earthworms were removed, the soil Cu content was estimated by disjunctive kriging. Cu concentration factors (ratio of Cu(W) to Cu(T)) in the field experiment were in excellent agreement with those of the laboratory experiment. This indicates that, with a sufficiently high sampling density, it may be feasible to predict earthworm Cu accumulation in the field using a concentration factor determined in the laboratory.

Journal Article↗
PubMed1998

Community representatives: representing the "community"?

This paper takes as its starting point the apparent disjunction between the assumptions of the self-evidence of the meaning of community in major international declarations and strategies which promote community participation and the observation that meanings of "community" are a subject of extensive debate in literatures of social analysis and to some extent health. Given that the word's meaning is not agreed, those working to promote "community participation" in health are forced to adjudicate on competing meanings in order to operationalise the notion. This raises questions about how this is done and what are the implications of particular choices for what may be achieved by the participating "community". This paper presents the findings of an empirical study which examined the manner in which ideas of "community" are operationalised by people engaged in encouraging community participation in health promotion in the context of the selection of members for health for all steering groups in healthy cities projects in the United Kingdom. It argues that the demands of the role of the "community representative" are such that particular interpretations of "community" achieve ascendance. The paper explores the consequences of the interpretation of "community" as part of the "voluntary sector" and argues that this may compromise one of the stated desired outcomes of community participation i.e. extending democracy in health decision-making.

Community Participation↗
PubMed1999

The power of the visible: the meaning of diagnostic tests in chronic back pain.

This article explores the meaning of diagnostic tests for people with chronic back pain. Lower back pain is one of the most common health problems in the US. Five to ten percent of the patients who visit a primary care provider for back pain ultimately develop a chronic condition. We draw on interviews with chronic back pain patients in Atlanta, Dallas and Seattle to argue that testing constitutes an important element in the legitimation of pain for these patients. We discuss three aspects that make testing an area of concern for patients: a strong historical connection between visual images and the medicalization of the interior of the body, a set of cultural assumptions that make seeing into the body central to confirming and normalizing patients' symptoms, and the concreteness of diagnostic images themselves. Our interviews show that when physicians cannot locate the problem or express doubt about the possibility of a solution, patients feel that their pain is disconfirmed. Faced with the disjunction between the cultural model of the visible body and the private experience of pain, patients are alienated not only from individual physicians but from an important aspect of the symbolic world of medicine. This paper concludes by suggesting that a fluid, less localized understanding of pain could provide a greater sense of legitimacy for back pain patients.

Adult↗
PubMed2001

NCD activation of tubulin polymerization.

Tubulin dimer (tT) was purified from turkey erythrocytes. The motor domain of Drosophila non-claret disjunctional protein, NCD(335-700), was expressed in E. coli and purified. At 37 degrees C in the presence of GTP, the rate of polymerization of tT to microtubule (tMt) is accelerated over threefold by the presence of NCD(335-700). At 10 degrees C, the rate of tT polymerization is increased from zero, within experimental error, in the absence of NCD(335-700) to rates near those observed at 37 degrees C when NCD(335-700) is present. The NCD(335-700) concentration dependence of the rate indicated the reactive species was NCD(335-700)(n).tT, with n approximately 2. At 10 degrees C in the absence of GTP, polymerization does not occur, but tT activates NCD(335-700) MgATPase activity 10-fold. For the same conditions, using mians-NCD(335-700), which is modified with 2-(4'-maleimidylanilino) naphthalene-6-sulfonic acid, the apparent K(D) for binding to tT is 2.3 x 10(-5) M in the presence of MgADP. Replacing ADP with AMPPNP or ATP has a negligible effect on K(D). Mians-NCD(335-700) binding to tMt is 10-fold stronger than to tT. The above data indicate NCD(335-700) binds at a functional site on tT. The stoichiometry is consistent with the formation of NCD(335-700)(2).tT which in vitro accelerates self-assembly initiation and/or polymerization by binding a second tT in a position favorable for tubulin-tubulin interaction. The data suggest that in vivo functional NCD binding to microtubule involves one motor domain binding to alpha- and beta-subunits at the interface of two different tubulin dimers in a protofilament.

Animals↗
PubMed1998

Information and third order ontology.

The question of 'a unified theory of information' is addressed from the logical position of many-valued ontologies. Information is described as an operational factor which forms a trans-contextural bridge between disjunct ontological systems (or monocontextures).

Information Theory↗
PubMed2000

Late onset of CAD gene amplification in unamplified PALA resistant Chinese hamster mutants.

In rodent cells, resistance to PALA (N-phosphonacetyl-L-aspartate) has always been found associated with amplification of the CAD gene (carbamyl-P synthetase, aspartate transcarbamylase, dihydro-orotase). We describe two PALA resistant Chinese hamster mutant cell lines in which amplification of the CAD gene was not present. The PALA resistant phenotype was stable when the cells were grown in non-selective medium. However, after prolonged growth in the presence of the same drug concentration used for selection, cells with increased CAD gene copy number and higher levels of resistance overrode the original population. In these cell populations, a heterogeneous organization of the CAD genes was revealed by fluorescence in situ hybridization on mitotic chromosomes indicating that the additional copies of the gene were generated in several ways, such as non-disjunction and breakage-fusion-bridge cycles. The clastogenic effect of PALA, evidenced as chromosomal aberrations in the cells grown in the presence of the drug, could have favored the late onset of the amplified mutants. It is tempting to speculate that, during the expansion of tumor populations, different drug resistance mechanisms, including gene amplification, could occur in succession and lead to the generation of cells highly resistant to chemotherapeutic agents.

Animals↗
PubMed2001

Variation of diastereoisomeric pyrrolizidine alkaloids in Pleurothallis (Orchidaceae).

The alkaloids of leaves and flowers of 18 populations of four Pleurothallis (Orchidaceae) species were characterized. Both leaves and flowers of individuals from all populations have two diasteroisomers of 1-hydroxymethylpyrrolizidine (RI=1290 and 1311). The 1290 isomer was the most abundant in all populations of P. johannensis (74-93%) and P. fabiobarrosii (63-93%), two morphologically closed species. On the other hand, in almost all populations of P. teres the 1311 isomer is the more abundant (61-95%), except in one population occurring disjunct from the core area distribution of the species. These results support the recent taxonomic revision for these three species. Almost all P. ochreata populations also have the 1290 as the most abundant isomer, except in one morphologically differentiated population situated at the southern extreme of the distribution of this species.

Journal Article↗
PubMed1997

Rare combination of Becker muscular dystrophy and Klinefelter's syndrome in one patient.

Becker muscular dystrophy (BMD) was diagnosed in a male patient with Klinefelter's syndrome (47, XXY karyotype). The BMD was confirmed by (i) immunohistological methods and Western blotting, showing decreased quantity of dystrophin in muscle biopsy specimen and (ii) molecular genetic analysis which demonstrated a homozygous deletion of exons 45-47 within the dystrophin gene on both X-chromosomes. The same deletion was found on one of the X-chromosomes in the patient's mother. It can be deduced therefore that Klinefelter's syndrome in this patient is most likely due to a non-disjunctional error which occurred either during the second maternal meiotic division or during early postzygotic mitotic divisions.

Adult↗