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The application of comparative genomic hybridization as an additional tool in the chromosome analysis of acute myeloid leukemia and myelodysplastic syndromes.

In acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) there are frequently complex karyotypes with multiple structurally altered chromosomes, many of which are marker chromosomes of unknown origin. The aim of this study was to apply comparative genomic hybridization (CGH) to cases of AML or MDS in transformation submitted for routine cytogenetic analysis to investigate whether this approach would yield any further information and, if possible, to predict which cases would benefit from CGH analysis. Nineteen cases with AML or MDS in transformation were analyzed. CGH revealed nine cases with gains or losses of chromosomal material. In six of these cases the chromosomal location of this material was not apparent from cytogenetic analysis especially when multiple markers were present. By using fluorescence in situ hybridization (FISH) with specific libraries for the chromosome regions that showed discordance between CGH and conventional cytogenetics, we were able to identify the chromosome location of material within the karyotype. In this group of six patients, four cases of an unbalanced translocation involving regions of chromosomes 5 and 17 were characterized. Three of these cases had additional abnormalities, including two cases with regions of amplification in which oncogenes are located (MYC, MLL) and one case with a dic(7;21)(p10;p10). In all six cases it was possible to characterize complex chromosomal aberrations such as derivative chromosomes, marker chromosomes, and ring chromosomes. This study demonstrates that CGH can detect true gain and loss of critical chromosome regions more accurately than conventional karyotyping in cases with very complex karyotypes, and can thus prove useful in predicting prognosis and pinpointing areas of the genome that require further study. Also, CGH can be a useful technique to identify the origin of marker chromosomes, and it can assist in choice of probes for confirmatory FISH, when there is no clue provided from the analysis of G-banded chromosomes.

Acute Disease↗

Realities of high-throughput liquid chromatography/mass spectrometry purification of large combinatorial libraries: a report on overall sample throughput using parallel purification.

We report on the development of a validated, streamlined high-throughput process for the purification of parallel-synthesis-derived combinatorial libraries. The steps involved in this library purification process include dissolution of dry films of crude synthetic material, dual-column LC/MS purification, dual-column postpurification analysis, quantitation, reformatting, and submission of pure compounds for registration. Although the purification and postpurification analysis times decreased essentially linearly as a function of the number of HPLC columns employed, it was not possible to decrease the total purification process time linearly as a function of the number of columns employed in the system. This was due primarily to the fact that numerous steps in the total purification process are independent of sample analysis and purification (e.g., evaporation, reconstitution, and reformatting, etc.). Additionally, experiments were also performed to assess whether separate gradient pumps were necessary for each channel of this two-channel LC/MS or if acceptable results could be reliably obtained by splitting the flow from one set of gradient pumps between two HPLC columns. On the basis of the parallel, two-column LC/MS system employed in this work, throughput estimates were extrapolated to more massively parallel systems (e.g., four-channel LC/MS).

Amino Acids↗

VIJB: a companion of the JBROWSE genome browser for the visually impaired people.

MOTIVATION: The availability of touch-sensitive and haptic devices has been a keystone development for the inclusion of visually impaired people (VIPs) in modern, highly digitized work environments. Braille displays have proven efficient and versatile enough to parse large and complex text files, making bioinformatics and text-heavy programming accessible to VIPs. However, the complex graphical objects -combining numerous datasets- typically generated during data integration remain challenging, even with the aid of descriptive AI. This is particularly true in functional genomics. Here, we present VIJB, a simple application that displays the multilayered output of the JBROWSE genome browser on a Braille reader, enabling VIPs to fully participate in data integration in functional genomics. AVAILABILITY AND IMPLEMENTATION: VIJB is programmed in Python and relies on the scientific library NumPy, the braillegraph and pyBigWig libraries, and the TABIX software. The architecture is summarized in Supplementary Material 1, available as supplementary data at Bioinformatics online. VIJB is available for download at the GitHub repository https://GitHub.com/NiBuMNHN/VIJB and is licenced under the GPL 3.0.

Persons with Visual Disabilities↗

Does Danshen improve disability after acute ischaemic stroke?

OBJECTIVES: Danshen, a Chinese herb, has been used as a standard treatment for acute ischaemic stroke in China. This study assesses the quality of all randomized control trials (RCTs) comparing Danshen of any preparation to without Danshen (placebo or other western or herbal medicines), and to evaluate its effectiveness in improving disability. MATERIALS AND METHODS: Systematic review through literature search in MEDLINE, Cochrane Library, China Biological Medicine Database and others. The main outcome measure is disability improvement on the Chinese National Disability Scale (CNDS) at 2 weeks after intervention. RESULTS: Of 33 Danshen control trials for acute ischaemic stroke identified in the literature, none were placebo-controlled. Eleven RCTs comparing Danshen with one of seven Western and two herbal medicines met the inclusion criteria for review, however, these studies were of poor quality. Compared with the nine medicines, the effect of Danshen was inferior in five trials and not significantly different in another six trials. For the two trials comparing Danshen with Buflomedil, the combined odds ratio (OR) was 0.27 (95% CI: 0.12-0.61) favouring Buflomedil, but the test of homogeneity revealed heterogeneity (P = 0.083). For the two trials comparing Danshen with Naloxone, the combined OR was 0.16 (95% CI: 0.07-0.40) favouring Naloxone. However, none of the nine medicines per se has been proven effective in post-stroke disability improvement. CONCLUSIONS: The existing Danshen RCTs are not placebo-controlled and are of poor quality, therefore, there is no substantial evidence that Danshen is effective. Systematic review on RCTs comparing Danshen with other medicines does not support the notion that Danshen may be beneficial to disability improvement after acute ischaemic stroke.

Acute Disease↗

Allergens in school settings: results of environmental assessments in 3 city school systems.

Environmental allergens are major triggers for pediatric asthma. While children's greatest exposure to indoor allergens is in the home, other public places where children spend a large amount of time, such as school and day care centers, may also be sources of significant allergen encounters. The purpose of this article is to describe schoolroom allergen levels from 3 different geographic sites obtained from dust samples collected in the fall and in spring. Environmental dust samples were collected from elementary schools in Birmingham (AL), Detroit (MI), and Houston (TX), from 4 room locations, including the cafeteria, library, upper grades, and lower grades. Samples were assayed for dust mite (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cat (Felis domesticus), and cockroach (Blatella germanica 2) allergen levels. Allergen levels varied by geographic location and type of schoolroom. Schoolroom settings differed by the type of flooring (hard and carpet), room characteristics and use (food service, library shelves with books, and general classroom with multiple types of materials [individual desks and different types of furniture]), and the average age of the schoolroom dwellers (younger vs. older children). Dust mite, cat, and cockroach allergens were present in all schoolrooms and all sites at varying levels by season and by type of room. Schools may be important sources of direct allergen exposure and reservoirs that could potentially contribute to allergic sensitization and disease exacerbation in children. Further studies are needed to carefully examine the environmental allergen load in schools and its effect on children.

Air Pollutants↗

Specificity rescue and affinity maturation of a low-affinity IgM antibody against pro-gastrin-releasing peptide using phage display and DNA shuffling.

The objectives of the present study were to use phage display to rescue the specificity of an IgM antibody and by the use of DNA shuffling to construct a sublibrary from which mutants with higher affinity could be selected. As a test system, a hybridoma cell line producing low-affinity IgM against recombinant pro-gastrin-releasing peptide (ProGRP) was chosen as starting material for construction of a single-chain Fv (scFv) phage library. One clone, pGRP5, demonstrating affinity for the antigen, was selected for the study. Random mutations were introduced into the scFv sequence by DNA shuffling, and mutants with raised affinity were selected by biopanning against recombinant ProGRP. Clones with affinities improved by approximately two orders of magnitude were selected after the first round of DNA shuffling. An additional 8- to 9-fold rise in affinity was demonstrated in mutants after the second round of mutagenesis. Sequence analysis demonstrated changes primarily in the complementarity-determining region (CDR) H1, CDR L1 and CDR H3 as compared to the original clone. Thus, by the use of phage display in combination with DNA shuffling, the specificity of an IgM antibody was rescued and the affinity was raised almost three orders of magnitude.

Animals↗

Internet resources available to otolaryngologists.

During recent years, the Internet has evolved into the largest computer network in the world, allowing access to vast amounts of information and services. Medical information is increasingly available to both patients and professionals, and ever more biomedical resources are becoming available on-line to assist in research, clinical medicine, and education. The Internet has always provided useful resources to otolaryngologists, implemented at various academic departments and national organizations or by specialists or specific medical web sites offering technical, scientific, and biomedical information. The purpose of this article is to provide as complete a list as possible of the World Wide Web sites accessible through the Internet that are of interest to otolaryngologists. It summarizes different types of resources available, including educational material, audiology sites, outcomes research, discussion lists, research laboratories, publications, medical libraries, news and medical conferences, organizations, academic departments, otolaryngological and medical resources, medical and surgical equipment and suppliers, and miscellaneous other sites of interest to otolaryngologists. This review is intended to present the wealth of the accessible information on the Internet and to promote the use of the network to otolaryngologists who do not have extensive experience in computers or telecommunications.

Computer User Training↗

Application of multidimensional scaling to preformulation sciences: a discriminatory tool to group microcrystalline celluloses.

Pre-formulation studies constitute the first step of any pharmaceutical product development and manufacture. Establishment of a comprehensive library of critical physical, chemical, biological and mechanical properties of all materials used for a formulation can be costly, tedious and time consuming, despite its importance in quality manufacturing management. This study seeks to demonstrate the pharmaceutical application of multidimensional scaling (MDS) by incorporating it as a pre-formulation tool for grouping an expanded range of microcrystalline celluloses (MCC). MDS presents the various MCC grades in two-dimensional space based on their torque rheological properties; thus conferring an extra dimension to the pre-formulation tool to facilitate the visualization of the relative positions of each MCC grade. Through this work, the utility of MDS for expediting pre-formulation studies, in particular, grouping of excipients that are available in different brands and grades can be amply exemplified.

Cellulose↗

Introducing health sciences librarians to the Internet.

The Internet is no longer just for the adventurous explorers or the technical experts--it has found its way into the mainstream of librarianship. New users are coming onto "the net" in droves. A wealth of information is currently available dealing with the mechanics of the Internet and there are general guides to the available resources. More work needs to be done, however, in developing subject specific materials. This paper will report on the strategy that Scott Memorial Library, Thomas Jefferson University, has employed to develop staff skills and awareness and to take advantage of the resources and opportunities that the network provides for the health sciences community.

Academic Medical Centers↗

Group for research in pathology education online resources to facilitate pathology instruction.

BACKGROUND: The Group for Research in Pathology Education (GRIPE) is an organization of pathology educators whose purpose is to promote and facilitate excellence in pathology education. One important function of GRIPE is the maintenance of image and multiple-choice test question data banks. These resources have recently been made available online via the GRIPE Digital Library Web site. The purpose of the GRIPE Digital Library project was to develop an online searchable database that would facilitate access to the GRIPE resources for pathology education. DESIGN: The GRIPE image bank--containing approximately 3000 peer-reviewed gross and microscopic pathologic images along with textual descriptions--was linked with the GRIPE test question bank using Gossamer Thread's DBMan Web database management program. The search and display templates create a functional user interface that integrates images, image descriptions, and test questions into a single online digital library. Using any Web browser, faculty can access the GRIPE Digital Library and search for images and/or test items that can be used in teaching. RESULTS: In the first 18 months (February 2000 through July 2001), users at 40 GRIPE member institutions signed up and used the GRIPE Digital Library to perform more than 6000 individual searches and view more than 37500 images. These digital images were used to produce lectures and laboratory modules that were posted on Web pages and made available to students remotely. CONCLUSIONS: The GRIPE Digital Library provides a unique resource that can facilitate development of educational materials for pathology instruction and helps to fulfill the educational mission of GRIPE.

Computer Communication Networks↗

Community drug information services by telephone.

Counseling patients on the use of their medications is a direction the pharmacy profession has taken in recent years. The location of this interaction generally is assumed to be within the confines of a pharmacy or institutional setting. The concept can be expanded in scope and service to the community by encouraging drug information requests by telephone. A representative reference library and a form to document each call are the essential materials needed to begin. Exercising good judgment and a clinical approach to each call ensures the best possible outcome.

Community Health Centers↗

[Is thrombolytic therapy effective in stroke?].

BACKGROUND: The Norwegian Centre for Health Technology Assessment was asked to assess the treatment of stroke by trombolytic medication. We were also asked to include an evaluation of potential consequences for the organisation of the health care system. MATERIAL AND METHODS: Relevant literature was identified on Medline, the Cochrane Library (Systematic Reviews), and INAHTA (Systematic Reviews). Of particular importance are one study from the USA and two studies originating in Europe. RESULTS: The conclusion of the working group is that the benefit of thrombolytic treatment in the studies assessed is uncertain; furthermore, intracranial haemorrhage can occur as a complication of the treatment. INTERPRETATION: Future thrombolytic treatment of stroke patients should be carried out according to a research protocol with thorough documentation of effects as well as side effects.

Controlled Clinical Trials as Topic↗

[The risk of defects in the neural tube caused by valproic acid and carbamazepine].

OBJECTIVE: To determine the risk, if any, of carbamazepine and valproic acid use on the foetus with respect to neural tube defects. MATERIALS AND METHODS: Databases such as MEDLINE, EMBASE, SCISEARCH, The Cochrane Library and LILACS were consulted to have access to published literature from January 1966 to September 2004. All articles published in English and Spanish were considered. A manual review of the references presented in each produced article was done in order to identify the articles that the electronic search may have not found itself. However, articles which seemed ambiguous as to the title and/or abstract were completely analyzed to establish their relevance. Studies that examined the effects of systematic exposure to carbamazepine or valproic acid during pregnancy and that assessed neural tube defects in the infants were eligible. The data was extracted in the form of 2 x 2 tables. The odds ratio (OR), relative risk (RR) and 95% confidence interval (CI) was calculated for each of the studies. RESULTS: The pooled relative risk of neural tube defects among the exposed to valproic acid was 0.61 (95% CI: 0.06-6.72). The risk among the exposed to carbamazepine was 1.10 (95% CI: 0.16-7-75). CONCLUSIONS: Due to the methodologic limitations of most of the studies where the data was insufficient, only three studies could be included in the meta-analysis. There is not enough evidence to establish the risk raised in the objective of the study.

Anticonvulsants↗

[J.M. Charcot's (1825-1893) method].

The aim of this study is to show the various aspects of Charcot's methodology from examples provided by Charcot's publications in the field of geriatrics. The source material consists of unedited Charcot's manuscripts, stored in Charcot's library at the Salpêtrière hospital, in Paris. Mainly inspired by Müller's and Virchow's methodologic pattern, J.M. Charcot filled the gap which concerned French medicine, in the middle of the nineteenth century, when the rhythm of its discoveries decreased. Charcot substituted successfully the old Parisian 'hospital medicine' for new features of medicine initiated by German doctors. Charcot's methodology implied also a new scientific theory in medicine.

France↗

The tissue inhibitor of metalloproteinases-3 gene in breast carcinoma: identification of multiple polyadenylation sites and a stromal pattern of expression.

BACKGROUND: Tissue inhibitor of metalloproteinases-3 (TIMP3) is the third member of the TIMP family of proteins, believed to play a significant role in controlling extracellular matrix remodeling. MATERIALS AND METHODS: Differential screening of a human breast carcinoma cDNA library using substracted and PCR-amplified cDNA probes identified a 4.6-kb TIMP3 cDNA, which was used for further cDNA library screenings, Northern blot hybridizations, and the synthesis of riboprobes for in situ RNA hybridization analyses. RESULTS: The 4.6-kb full-length TIMP3 cDNA contains 3.7 kb of 3'-untranslated sequence. Additional TIMP3 cDNAs subsequently identified were colinear with the original sequence, but revealed use of four different polyadenylation signals within the 3'-untranslated region, which accounted for the 4.6-, 2.7-, 2.5-, and 2.1-kb TIMP3 transcripts noted in this and in previous studies. In situ RNA hybridizations demonstrated that in breast carcinoma the TIMP3 gene was predominantly expressed by fibroblastic cells within the tumor stroma adjacent to cancer cells. TIMP3 transcripts were also strongly detected in fibroblastic decidual cells of pregnant endometrium. CONCLUSIONS: Modulating the length of the 3'-untranslated region may represent a mechanism by which TIMP3 gene expression is controlled in tissues. The strong expression of the TIMP3 gene by fibroblastic cells in breast carcinoma supports the importance of tumor stroma as a source of factors influencing human carcinoma growth and progression.

Breast Neoplasms↗

Application of HPLC with photodiode array detection for systematic toxicological analyses of drug groups.

During four years experience high performance liquid chromatography (HPLC) with photodiode array detection has been proved to be the demanded method of systematic toxicological analysis (STA) for unknown drugs in biological sample because of separation efficiency, sensitivity, flexibility and identification potential. HPLC can be an easy way of quantitation as well. Ultraviolet spectra acquired with Waters 990+ photodiode array detector together with retention data are used to identify unknown or suspected drugs and metabolites in various biological material often after basic TLC examination of urine. At present spectrum library used for comparison involves 180 spectra of standards in acid and neutral media. Various sample preparation procedures have been tested and till now eight isocratic liquid chromatographic systems have been used routinely for sensitive screening in small samples, identification and/or quantitative assays of drug groups. These analytical systems are suitable for toxicological examinations of forensic cases, acute poisonings, drug abuse. They are convenient to subsequent monitoring of serum drug levels during treatment of an intoxication as well.

Chromatography, High Pressure Liquid↗

Classification systems used in medical libraries.

The present study identifies the classification systems used in 941 libraries. It explores the reasons behind the choice of the National Library of Medicine Classification by 589 libraries. Reclassification procedures were investigated through a questionnaire sent to twenty-five libraries that have changed to NLM since 1959. Statistics and replies are given on: the classification systems employed prior to reclassification; the use of broad or specific Library of Congress class numbers in the LC schedules outside the scope of the NLM schedules; the number of catalogers in each library doing the reclassification; the use of cut-off dates for retrospective materials; the adoption of MeSH headings; user preference; and cost differences. Chief reasons for the change to NLM proved to be local circumstances, currency, arrangement of subclasses by NLM, its dovetailing with the LC Classification, and reliance upon nationally centralized cataloging services.

Book Classification↗

Micro-X-ray fluorescence as a general high-throughput screening method for catalyst discovery and small molecule recognition.

A powerful high-throughput screening technique is described for the rapid screening of bead-based libraries for catalyst discovery and molecular recognition. Micro-X-ray fluorescence (MXRF) screens materials for elemental composition with mesoscale analysis. This method is nondestructive and requires minimal sample preparation and no special tags for analysis, and the screening time is dependent on the desired sensitivity. The speed, sensitivity, and simplicity of MXRF as a high-throughput screening technique were applied to screen bead-based libraries of oligopeptides for phosphate hydrolysis catalysts and molecular recognition of selective receptors for the degradation products and analogues of chemical warfare agents. This paper demonstrates the analytical or HTS capability of MXRF for combinatorial screening. It is meant only to show the capabilities of MXRF and is not meant as an exhaustive study of the catalyst and molecular recognition systems presented.

Catalysis↗