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PubMed1990

[Physiopathology of neural death and of gliosis].

From a neurobiological point of view, three aspects have to be considered when elaborating a therapeutic strategy to improve functional recovery after an acute lesion of the central nervous system: prevention of secondary neuronal death and axonal lesions, stimulation of nerve cells regeneration and neuronal replacement by grafting. Two aspects of our research program will be discussed in this lecture: 1. The pathophysiology of secondary neuronal death. We will focus on a neuronotoxic activity released by astrocytes and whose presently established properties suggest its involvement in the pathophysiology of secondary cell death. These data open new prospects for the pharmacological approach of neuroprotection. 2. The pathophysiology of astrogliosis: our data suggest that the neuronal control of type one astrocytes proliferation is twofold: normal neurons release a proliferation inhibition factor (a 17 Kd protein for which we suggest the name astrostatine) while injured neurons release one or several astroglial mitogens.

Astrocytes↗

PubMed2004

Body condition scores and dairy form evaluations as indicators of days open in US Holsteins.

The objectives of this study were to estimate genetic correlations among body condition score (BCS), dairy form, milk yield, and days open in US Holsteins and investigate the potential of using BCS or dairy form evaluations as early indicators of days open. Dairy form and BCS obtained from the Holstein Association USA, Inc., were merged with mature equivalents (ME) for milk yields and days open data from AIPL-USDA. Cows were required to be classified between 24 and 60 mo of age, before 335 d in milk (DIM) and have ME milk of at least 4537 kg. A minimum of 20 daughters per sire and 10 cows per herd-classification visit (HV) or herd-year-season of calving (HYS) were required. The final data set included 159,700 records. Heritabilities and correlations among dairy form, BCS, milk yield, and days open were estimated with multiple trait sire models. Fixed effects included age at classification for dairy form and BCS, age at calving for milk yield, HV for dairy form and BCS, HYS for milk yield and days open, DIM within lactation group for dairy form and BCS and lactation group for milk yield and days open. Correlations among dairy form, BCS, and days open were generated with and without a ME milk covariable. Correlations between ME milk and days open were generated with and without covariables for dairy form or BCS. Random effects included sire and error. The genetic correlation estimates of days open with dairy form, BCS, and ME milk were 0.48, -0.30, and 0.38, respectively. The genetic correlation estimate between days open and dairy form was 0.38 after adjustment for ME milk, whereas the genetic correlation between days open and BCS was -0.24 after adjustment for ME milk. Combining dairy form evaluations with days open evaluations for 19 recently proven bulls resulted in an average increase of 0.06 for reliability of days open evaluations. The addition of BCS evaluations did not increase reliability when dairy form observations were available.

Aging↗

PubMed1997

Data linkage methods used in maternally-linked birth and infant death surveillance data sets from the United States (Georgia, Missouri, Utah and Washington State), Israel, Norway, Scotland and Western Australia.

In this paper we describe the methods used to link birth and infant mortality and morbidity surveillance data sets into sibships using deterministic or multistage probabilistic linkage methods. We describe nine linked data sets: four in the United States (Georgia, Missouri, Utah and Washington State), and four elsewhere (Scotland, Norway, Israel and Western Australia). Norway and Israel use deterministic methods to link births and deaths into sibships. The deterministic linkage is usually dependent on the availability of national identification numbers. In both countries they assign these numbers at birth. Deterministic linkage is usually highly successful, and the major problem is the validation of linkages. In the United States, Western Australia and UK linkage is multistage and probabilistic. This approach is usually dependent on the calculation linkage weights from sociodemographic variables. The success rates of probabilistic methods are above 80%. Maternally-linked perinatal data open new vistas for epidemiological research. Recurrence of poor perinatal outcomes is more appropriately studied using longitudinally-linked data sets. In addition, the emergence of risk factors and the recurrence of risk factors can be studied.

Epidemiologic Methods↗

PubMed1996

Application of dimension estimation and surrogate data to the time evolution of EEG topographic variables.

Dimensional complexity (estimated correlation dimension) was measured for two topographic EEG time series: (a) the time evolution of global field power (GFP) and (b) the time evolution of sequential dissimilarity (SQD) for resting, eyes-closed and eyes-open data. Eyes-closed GFP and eyes-closed/open SQD all had an element of nonlinearity in their dynamics as evidenced by increased dimensional complexity associated with the phase-angle randomization, Gaussian surrogate-data procedure. However, none of the three gave any evidence of being deterministic chaotic processes. Eyes-open GFP dimensional complexity could not be distinguished from a linear-stochastic process.

Adult↗

PubMed2002

Correction of probe pressure artifacts in freehand 3D ultrasound.

We present an algorithm which combines non-rigid image-based registration and conventional position sensing to correct probe-pressure-induced registration errors in freehand three-dimensional (3D) ultrasound volumes. The local accuracy of image-based registration enables the accurate freehand acquisition of high resolution (>15 MHz) 3D ultrasound data, opening the way for 3D musculoskeletal examinations. External position sensor readings guarantee the large-scale positional accuracy of the data. Pressure correction is shown to dramatically increase the perceived quality of extended-field-of-view data sets and reslices through volumetric data sets, while quantitative comparisons of multiple in vivo volumes demonstrate the superior precision of the corrected data.

Algorithms↗

PubMed2001

Rapid cycling bipolar disorder.

Rapid cycling bipolar disorder (RCBD) is defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) as a type of manic-depressive illness in which the patient experiences four or more episodes of mania and/or major depression per year. It was first reported as a consequence of the reduced effectiveness of lithium carbonate in the treatment and prophylaxis of this form of bipolar disorder (BD) in contrast to those with less frequent cycling. Among the anticonvulsants, there have been reports with different degrees of controlled data concerning carbamazepine, valproate, lamotrigine, topiramate, gabapentin and primidone. There is a paucity of double-blind studies, but what is available supports the use of lamotrigine. There is open data supporting the use of carbamazepine, valproate and topiramate. Regarding other classes, nimodipine may have specific utility in ultradian- (ultra-ultra-) or ultra-RCBD and there is double-blind data regarding the specific utility of olanzapine in RCBD. Low thyroid function may be a factor in development of RCBD; therapies aimed at elevating thyroid levels, even beyond the usual range, have frequently produced benefits in open trials. More research is needed into the possible therapeutic benefits of verapamil, bupropion, choline, light therapy and electroconvulsive therapy (ECT).

Anticonvulsants↗

PubMed2003

Management of isthmic spondylolisthesis with posterolateral endoscopic foraminal decompression.

STUDY DESIGN: Prospective evaluation of 24 consecutive patients with isthmic spondylolisthesis with chronic back, buttock, and leg pain treated by endoscopic foraminal decompression and followed for a minimum of 2 years. OBJECTIVES: To assess the efficacy of endoscopic foraminal decompression and mobilization of the exiting and transiting nerves, discectomy, ablation of osteophytes, and impinging pars as a means of treatment by the posterolateral approach. SUMMARY OF BACKGROUND DATA: Open decompression with or without fusion is a commonly accepted procedure for symptomatic isthmic spondylolytic spondylolisthesis in patients who fail to respond to conservative treatment. There is no published data on the outcome of endoscopic procedures for this condition. METHODS: Endoscopic foraminal decompression achieved with laser-assisted bone and soft-tissue ablation was performed on 12 males and 12 females with an average age of 42.4 years (36-72 years) followed for an average period of 34 months (28-46 months). The average preoperative duration of symptoms was 6.1 years (3-9 years). RESULTS: One hundred percent cohort integrity was maintained at the final follow-up. Results were analyzed using the percentage change in Oswestry Disability Scores and in Visual Analogue Pain scores. Using a percentage change in Oswestry Disability Score of 50 or more plus VAP scores of 50 or more to determine good and excellent outcomes, 79% (19 out of 24) exceeded this value. CONCLUSION: Laser-assisted endoscopic foraminal decompression provides a minimalist means of exploring the extraforaminal zone, the isthmic defect, the foramen and its contents, the disc and the epidural space. It allows adequate resection with decompression and discectomy, without the need for open decompression and fusion, and targets the symptomatic level effectively in patients with Grade I-III isthmic spondylolisthesis.

Adult↗

PubMedDate not supplied

XML-based visualization of design and completeness in medical databases.

PURPOSE: mdplot (medical database plot) visualizes both structure and quality of data in medical databases by means of a summary representation of design and completeness in XML format. The goal is to identify attributes suitable for evaluation and to aid in creating open data models. METHODS: A three-stage visualization approach is applied. First, an overview of all classes in a database, second a detailed view of a specific class and third an analysis of individual attributes. Missing data is identified to enable specific efforts to improve data quality prior to analysis. For each class number of patients, attributes, and records per patient are provided. A condensed bar chart for each category of attributes (categorical, numerical, text and other) visualizes available content: The abscissa corresponds to the sequence of attributes; the ordinate represents completeness per attribute. By selection of a specific class, a detailed description is provided including mean completeness in each category as well as completeness per attribute. To analyse attributes that are collected at several time points per patient, a frequency distribution of records per patient can be generated. RESULTS: The new methodology was applied to two clinical research databases consisting of 292 attributes (955 patients) and 224 attributes (610 patients), respectively, and resulted in major restructuring of the systems. A public website is provided for generation of mdplots.

Data Collection↗

PubMed1994

Steps to collaboration.

Although collaboration is a much sought-after goal among health care professionals, minimal research has clarified the essential communication elements (behaviors) necessary for collaboration. This series of research studies, grounded in the pragmatic perspective, represents a beginning attempt to identify these behaviors. A total of 270 practicing physicians and nurses responded to open-ended questions and/or a survey assessing the communication elements of content; relationship (aggressive, affirming, and collaborative styles); and opportunity to communicate. Findings suggest elements necessary for collaboration include reliable presentation of relevant data, openness to information presented, and adequate time to communicate. Differences were noted between nurses and physicians as to the relative importance of these behaviors.

Communication↗

PubMed2003

Review of analytical methods for prospective cohort studies using time to event data: single studies and implications for meta-analysis.

Prospective cohort studies are extremely important in epidemiological research as they give direct information on the sequence of events, which can be used to demonstrate causality. They also have the advantage that many diseases can be studied simultaneously. However, they are usually very time consuming and expensive to run. In addition, practitioners of evidence-based medicine prefer to make decisions based on several studies rather than a single study, hence the need for meta-analysis. The use of meta-analyses in order to synthesize the evidence from randomized controlled trials is extremely popular in medicine and is also being utilized increasingly in epidemiology. The statistical methodology for meta-analyses of epidemiological studies is a long way behind in terms of the advances made in the methodology for randomized controlled trials. Numerous methodological issues, particularly in respect to dealing with biases inherent in these types of studies, have made the results of meta-analyses of epidemiological studies that use summary data open to criticism. This review mainly concentrates on analytical methods for prospective cohort studies that have survival outcomes. In addition, the implications for meta-analysis assuming that the analyst has access to individual participant data are also discussed. The approaches are described with respect to underlying theory and assumptions. It is hoped that this review will promote the use of these approaches in meta-analyses conducted in epidemiology as well as providing some directions for future research.

Cohort Studies↗

PubMed2004

HGVbase: a curated resource describing human DNA variation and phenotype relationships.

The Human Genome Variation Database (HGVbase; http://hgvbase.cgb.ki.se) has provided a curated summary of human DNA variation for more than 5 years, thus facilitating research into DNA sequence variation and human phenotypes. The database has undergone many changes and improvements to accommodate increasing volumes and new types of data. The focus of HGVbase has recently shifted towards information on haplotypes and phenotypes, relationships between phenotypes and DNA variation, and collaborative efforts to provide a global resource for genome-phenome data. Open sharing and precise phenotype definitions are necessary to advance the current understanding of common diseases that are typified by complex aetiologies, small genetic effect sizes and multiple confounding factors that obscure positive study results. Association data will increasingly be collected as part of this new project thrust. This report describes the evolving features of HGVbase, and covers in detail the technological choices we have made to enable efficient storage and data mining of increasingly large and complex data sets.

Computational Biology↗

PubMed1999

Complete structure of the chloroplast genome of Arabidopsis thaliana.

The complete nucleotide sequence of the chloroplast genome of Arabidopsis thaliana has been determined. The genome as a circular DNA composed of 154,478 bp containing a pair of inverted repeats of 26,264 bp, which are separated by small and large single copy regions of 17,780 bp and 84,170 bp, respectively. A total of 87 potential protein-coding genes including 8 genes duplicated in the inverted repeat regions, 4 ribosomal RNA genes and 37 tRNA genes (30 gene species) representing 20 amino acid species were assigned to the genome on the basis of similarity to the chloroplast genes previously reported for other species. The translated amino acid sequences from respective potential protein-coding genes showed 63.9% to 100% sequence similarity to those of the corresponding genes in the chloroplast genome of Nicotiana tabacum, indicating the occurrence of significant diversity in the chloroplast genes between two dicot plants. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.

Anticodon↗

PubMed2004

Bupreorphine:a new pharmacotherapy for opioid addictions treatment.

The federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with the disease of addiction by providing increased access to options for treatment. Previously, only methadone maintenance, approved for use only through specially regulated clinics, was available to treat opioid addiction. DATA allows any physician choosing to take a short specialty training course and become certified to prescribe buprenorphine. Buprenorphine and buprenorphine/ naloxone (Subutex, Suboxone) can be prescribed by certified physicians in a traditional office setting to treat patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and reducing illicit opioid use. Sublingual buprenorphine is more effective than clonidine or clonidine/naltrexone in short-term opioid detoxification treatment. Buprenorphine provides an additional tool to treat opioid addiction and improve the quality of lives of these patients. More physicians are needed to treat patients with addiction. DATA facilitates this by removing existing barriers and increasing access to treatment.

Biological Availability↗

PubMed1998

Structural analysis of Arabidopsis thaliana chromosome 5. VI. Sequence features of the regions of 1,367,185 bp covered by 19 physically assigned P1 and TAC clones.

Nineteen P1 and TAC clones, which have been mapped on the fine physical map of the Arabidopsis thaliana chromosome 5, were sequenced according to the shotgun-based strategy, and their structural features were analysed. The total length of the regions sequenced in this study was 1,367,185 bp. Combining this with the regions covered by 90 P1 and TAC clones previously reported, the total length of chromosome 5 sequenced to date becomes 8,058,855 bp. On the basis of similarity search against protein and EST databases and gene modeling with computer programs, a total of 330 potential protein-coding regions were identified, bringing an average density of the genes to approximately one gene per 4.1 kb. Introns were identified in 81.0% of the potential protein genes for which the entire gene structure was predicted, with an average number per gene of 4.2 and an average length of the introns of 180 bp. The RNA-coding genes identified were 9 tRNA genes corresponding to 8 amino acid species and 2 genes for U2 nuclear RNA. These sequence features are essentially identical to those in the previously reported sequences. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.

Arabidopsis↗

PubMed2003

An overview of recent findings of the Stanley Foundation Bipolar Network (Part I).

AIM AND METHODS: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. RESULTS: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. CONCLUSIONS: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden.

Antidepressive Agents↗

PubMed1997

Structural analysis of Arabidopsis thaliana chromosome 5. III. Sequence features of the regions of 1,191,918 bp covered by seventeen physically assigned P1 clones.

A total of 17 P1 and TAC clones each containing a marker(s) specifically mapped on chromosome 5 were isolated from P1 and TAC libraries of the Arabidopsis thaliana Columbia genome, and their nucleotide sequences were determined according to the shot gun-based strategy and precisely located on the physical map of chromosome 5. The total length of the clones sequenced in this study was 1,191,918 bp. As we have previously reported the sequence of 2,662,078 bp by analysis of 33 P1 clones, the total length of the sequences of chromosome 5 determined so far is now 3,853,996 bp. The sequences determined in this study were subjected to similarity search against protein and EST databases and analysis with computer programs for gene modeling, and a total of 310 potential protein-coding genes and/or gene segments with known or predicted functions were identified. The positions of exons which do not show apparent similarity to known genes were also predicted by computer-aided analysis. An average density of the assigned genes and/or gene segments was 1 gene/3,845 bp. Introns were identified in 78% of the potential protein genes, and the average number per gene and the average length of the introns were 3.7 and 185 bp, respectively. The numbers of the Arabidopsis ESTs matched to each of the predicted genes have been counted to monitor the transcription level. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.

Arabidopsis↗

PubMed1998

Structural analysis of Arabidopsis thaliana chromosome 5. VII. Sequence features of the regions of 1,013,767 bp covered by sixteen physically assigned P1 and TAC clones.

Sixteen P1 and TAC clones assigned to Arabidopsis thaliana chromosome 5 were sequenced, and their sequence features were analyzed using various computer programs. The total length of the sequences determined was 1,013,767 bp. Together with the nucleotide sequences of 109 clones previously reported, the regions of chromosome 5 sequenced so far now total 9,072,622 bp, which presumably covers approximately one-third of the chromosome. A similarity search against the reported gene sequences predicted the presence of a total of 225 protein-coding genes and/or gene segments in the newly sequenced regions, indicating an average gene density of one gene per 4.5 kb. Introns were identified in 72.4% of the potential protein genes for which the entire gene structure was predicted, and the average number per gene and the average length of the introns were 3.3 and 163 bp, respectively. These sequence features are essentially identical to those in the previously reported sequences. The sequence data and gene information are available on the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/arabi/.

Animals↗

PubMed1997

Cytosine methylation determines hot spots of DNA damage in the human P53 gene.

In the P53 tumor suppressor gene, a remarkably large number of somatic mutations are found at methylated CpG dinucleotides. We have previously mapped the distribution of (+/-) anti-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy -7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) adducts along the human P53 gene [Denissenko, M. F., Pao, A., Tang, M.-s. & Pfeifer, G. P. (1996) Science 274, 430-432]. Strong and selective formation of adducts occurred at guanines in CpG sequences of codons 157, 248, and 273, which are the major mutational hot spots in lung cancer. Chromatin structure was not involved in preferential modification of these sites by BPDE. To investigate other possible mechanisms underlying the selectivity of BPDE binding, we have mapped the adducts in plasmid DNA containing genomic P53 sequences. The adduct profile obtained was different from that in genomic DNA. However, when cytosines at CpG sequences were converted to 5-methylcytosines by the CpG-specific methylase SssI and the DNA was subsequently treated with BPDE, adduct hot spots were created which were similar to those seen in genomic DNA where all CpGs are methylated. A strong positive effect of 5-methylcytosine on BPDE adduct formation at CpG sites was also documented with sequences of the PGK1 gene derived from an active or inactive human X chromosome and having differential methylation patterns. These results show that methylated CpG dinucleotides, in addition to being an endogenous promutagenic factor, may represent a preferential target for exogenous chemical carcinogens. The data open new avenues concerning the reasons that the majority of mutational hot spots in human genes are at CpGs.

Base Sequence↗