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Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR.

Several organic anions are excreted into the bile via a canalicular multispecific organic anion transporter (cMOAT), which is hereditarily defective in mutant rats, such as the Eisai hyperbilirubinemic rat (EHBR) and TR- rat. In the present study, we cloned cMOAT from the Sprague-Dawley rat liver cDNA library based on the homology with human multidrug resistance-associated protein (hMRP). cMOAT was encoded by 4,623-base pair (bp) cDNA with a homology of 53.0 and 46.3% with hMRP at the cDNA and deduced amino acid level, respectively. The deduced amino acid sequence was the same as that cloned in Wistar rats (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996) except for four amino acid substitutions. By screening the library, three kinds of cDNA species for cMOAT with the same open reading frame and different 3'-untranslated region lengths (0.2, 1.5, and 3.5 kbp) were isolated. The Northern blot analysis of poly(A)+ RNA from the liver revealed that the expression of plural bands (approximately 5, 6, and 8 kb) was defective in EHBR, and this may be due to the presence of these cDNA species. Expression of cMOAT was observed almost exclusively in the liver and to a lesser extent in the duodenum, kidney, and jejunum. Reverse transcription-polymerase chain reaction (RT-PCR) and subsequent sequence analysis of EHBR liver, kidney, duodenum, and jejunum revealed that 1-bp replacement from G to A at nucleotide 2564 resulted in the introduction of the premature stop codon in all tissues examined. This mutation was different from that observed in TR (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996). Because EHBR and TR- are allelic mutants and both strains exhibit an autosomal recessive inheritance in the biliary excretion of organic anions it was concluded that the impaired expression of this particular protein is related to the pathogenesis of hyperbilirubinemia in the mutant animals.

Amino Acid Sequence↗

Creating the future: IAIMS planning premises at the University of Washington.

In September 1990, the University of Washington (UW) received a Phase I IAIMS Planning Grant from the National Library of Medicine and embarked upon a planning process involving the entire health sciences center. As a result of our relatively late entry into IAIMS planning, we have been able to learn from the experiences of other health sciences centers and to leverage our existing institutional efforts. Consequently, our progress has been rapid, and in a little over a year, we drafted a long-range plan and embarked on several related research and development projects. The hallmarks of our planning process include careful study of both the UW institutional environment and the experiences of other IAIMS institutions throughout the United States; broad, interdisciplinary participation of faculty, librarians, and administrators; an intensive educational process; a focus on people rather than technology; and, above all, leveraging of existing institutional and research projects that support our vision for the future.

Computer Communication Networks↗

Institutional constraints to building social science capability in public health research: a case study from Indonesia.

The promotion of social sciences capabilities in public health research in universities frequently encounters unexpected barriers. This paper argues that, in Indonesia, historic factors and institutional structures of public health research have created constraints to success in public health research and international technical assistance. Donors are often frustrated by apparent inconsistencies between agreed intentions and the subsequent behaviour of recipient colleagues, thus resulting in poor relations and failure of collaborative links. For social sciences to be integrated into public health research, assistance is needed in graduate education, library development, computerisation, and research methodology. Contributions in these areas may be ineffectual if they are not preceded or accompanied by efforts by recipients to reform or circumvent existing institutional weaknesses. Some important barriers to the development of research capabilities in Indonesia are beyond the control of individual faculties of public health, or even universities, and are affected by regulations and budgeting procedures of the National Department of Education and Culture, or the civil service administration. There are, however, changes that can be made at faculty or university level to encourage a more productive 'research culture' and promote linkages between the social and health sciences.

Humans↗

[Medical publications within private libraries of the European enlightenment. About the medically learned German novelist Johann Gottwerth Müller (1743-1828) and his stock of medical books].

The German novelist J. G. Müller is one of the popular writers of the late 18th century. The encyclopaedically educated scholar, from his point of view, is obliged to support publicly the welfare of state and society. Although Müller studied medicine he did not practise making his living from his novels which dealt critically with absolutist society. Medical studies and serious illness caused a lifelong interest in medical affairs ranging from the treatment of patients, the organisation of healthcare, the distribution of medicines, charlatanism, to everybody's responsibility for health. For him the syndrome of health/illness/medical science became part of the general status of science and a metaphor for the present and future conditions of class society. This engagement led to the compliation of approximately 280 medical books as part of his library which contained more than 13,000 volumes documented in the catalogue printed for public sale in 1829: "Verzeichnib der von dem Herrn Dr. Ph. Joh. Gottw. Müller in Itzehoe hinterlassenen Bibliothek, [...]/Contents of Joh. Gottw. Müller, Ph.D., library left behind in Itzehoe [...]."The essay comprises an introduction to Müller's collection of medical books and a complete bibliographical documentation. His books cover the medical discourse from the 17th to early 19th century focusing on publications of the 18th century. They offer information on medical bibliographies, catalogues, biographies, history of medical science, reference, specific publications on a large variety of actual topics such as medical science, treatment, politics, appliances, and social as well as hygienic questions. This stock of publications reveals itself as an additional source for an understanding of book-collecting in the 18th century, the history of privately organised medical libraries, and the discourse of medical science and treatment at a time of transition from a humoral-pathological to a firmer understanding of pathological concepts around 1800.

Book Collecting↗

Stuart Schreiber.

Stuart Schreiber is an Investigator at the Howard Hughes Medical Institute and Morris Loeb Professor in the Department of Chemistry and Chemical Biology at Harvard University. His chemical biology research, which uses small molecules derived from diversity-oriented synthesis, observational screens and information science, has uncovered principles that underlie information transfer and storage in cells. Harvard's ICCB and its affiliated, NCI-sponsored Initiative for Chemical Genetics and the NIGMS-sponsored Center of Excellence in Chemical Methodologies and Library Development are facilitating his research.

Career Choice↗

[Inequities in access to information and inequities in health].

This piece presents evidence that inequities in information are an important determinant of health inequities and that eliminating these inequities in access to information, especially by using new information and communication technologies (ICTs), could represent a significant advance in terms of guaranteeing the right to health for all. The piece reviews the most important international scientific research findings on the determinants of the health of populations, emphasizing the role of socioeconomic inequities and of deteriorating social capital as factors that worsen health conditions. It is noteworthy that Latin America has both socioeconomic inequities and major sectors of the population living in poverty. Among the fundamental strategies for overcoming the inequalities and the poverty are greater participation by the poor in civic life and the strengthening of social capital. The contribution that the new ICTs could make to these strategies is analyzed, and the Virtual Health Library (VHL) is discussed. Coordinated by the Latin American and Caribbean Center on Health Sciences Information (BIREME), the VHL is a contribution by the Pan American Health Organization that takes advantage of the potential of ICTs to democratize information and knowledge and consequently promote equity in health. The "digital gap" is discussed as something that can produce inequity itself and also increase other inequities, including ones in health. Prospects are discussed for overcoming this gap, emphasizing the role that governments and international organizations should play in order to expand access to the global public good that information for social development is.

Caribbean Region↗

Amphetamines for improving recovery after stroke.

BACKGROUND: Experimental animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effect were similar in humans, amphetamine treatment could have a major impact on recovery from stroke. OBJECTIVES: The objective of this review was to assess the effects of amphetamine treatment in patients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2002). In addition, we searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 2002), MEDLINE (1966-September 2002), EMBASE (1980-November 2002), and Science Citation Index (1992-December 2002). The reference lists of all relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies. SELECTION CRITERIA: Randomized unconfounded trials comparing amphetamine with placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Seven studies involving 172 patients were included. The quality of the trials varied but was generally high. Based on two trials (85 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto's odds ratio, [Peto OR] 1.54; 95% Confidence Interval [CI] 0.64 to 3.73). In these two trials, there were imbalances at baseline, with more serious strokes allocated to amphetamine. This imbalance may account for the trend for more deaths at the end of follow-up among amphetamine allocated patients (Peto OR 3.33; 95% CI 0.99 to 11.24). Based on 4 studies (95 patients) there was evidence of a better relative change in motor function according to the Fugl-Meyer motor scale (Weighted Mean Difference, [WMD] -8.17 points; 95% CI -13.58 to -2.76) and based on 1 study (21 patients) there was evidence of a better change in language function as assessed by the Porch Index of Communicative Ability score (WMD -7.51 points; 95% CI -14.42 to -0.60) in amphetamine allocated patients. REVIEWER'S CONCLUSIONS: At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor and language function, and the non-significant trend towards increased risk of death, could be related to imbalances in prognostic variables or other bias in studies. Further research in this area is therefore justified.

Amphetamines↗

Contributions of liquid chromatography-mass spectrometry to "highlights" of biomedical research.

Combined chromatographic and mass spectrometric techniques and in particular liquid chromatography-mass spectrometry (LC-MS) have been contributing in a decisive way to the progress of life sciences in general. Thus, the number of document entries in the US National Library of Medicine (MEDLINE) for articles dealing with LC-MS was 738 in 1991 and 2285 in 2001, with a total of 13 147 for the whole 10-year period, an increase of 310%. From these figures, we can ascertain that the total usage of combined LC-MS techniques is of the order of 40% relative to all of the MS publications collected in MEDLINE for the same period. However, from the perspective of real advances in medicine, it becomes difficult to identify what is outstanding in this field. The aim of this review was not to provide another LC-MS review, but an overview of the current status of the presence, visibility and impact of combined LC-MS techniques in biomedical research. The idea being to spot "highlight" literature contributions with the potential to become in the short or medium term real assets in a doctor's daily medical practice. In other words, after several truly remarkable technical achievements reported within the past decade, are we any closer to making LC-MS a useful and practical diagnostic tool for molecular diagnostics and personalized medicine? To approach this question, a literature survey was carried out to define: (i) the presence of LC-MS in the biomedical literature (MEDLINE) and its weight relative to the whole field of biological and biomedical mass spectrometry; (ii) the role of LC-MS in recent milestone biomedical contributions; and (iii) the present and future role of new LC-MS technology in medical diagnosis.

Biomedical Research↗

Structure and expression of the orphan nuclear receptor SHP gene.

To determine the organization of the orphan nuclear receptor SHP gene (Seol, W., Choi, H.-S., and Moore, D.D. (1996) Science 272, 1336-1339), genomic clones were isolated from human and mouse genomic libraries. The SHP gene was composed of two exons interrupted by a single intron spanning approximately 1.8 kilobases in human and 1.2 kilobases in mouse. Genomic Southern blot analysis and fluorescence in situ hybridization of human metaphase chromosomes indicated that the SHP gene is located at the human chromosome 1p36.1 subband. The 5'-flanking regions of human and mouse SHP genes were highly conserved, showing 77% homology in the region of approximately 600 nucleotides upstream from the transcription start site. Primer extension analysis was carried out to determine the transcription start site of human SHP to 32 nucleotides downstream of a potential TATA box. The human SHP gene was specifically expressed in fetal liver, fetal adrenal gland, adult spleen, and adult small intestine. As expected from this expression pattern, the activity of the mouse SHP promoter measured by transient transfection was significantly higher in the adrenal-derived Y1 cells than HeLa cells.

Animals↗

Research methodology and applied statistics. Part 2: the literature search.

This paper presents a basic methodology for an effective and efficient retrieval and recording of written materials in a subject area. The purpose of the literature review is examined and the criteria for selection of materials for inclusion are outlined. The methodology then describes the role of the librarian, various types of information resources, how to choose appropriate indexing and abstracting services, and a simple efficient method of recording the items found. The importance and use of Medical Subject Headings for research in physiotherapy is emphasized. A survey of types of book materials and how to locate them is followed by a detailed description of the most useful indexing and abstracting services available, in particular, the publications of the National Library of Medicine, notably Index Medicus, as well as Excerpta Medica and the Science Citation Index. A discussion of on-line search services, their coverage and availability in Canada, concludes the review of information sources. Finally, guidelines for selecting and summarizing the materials located and comments on the literary style for a review are supplied.

Documentation↗

Audiovisual materials: a survey of bibliographic controls in distributors' catalogs.

The current pattern of bibliographic control in audio-visual distributors' catalogs is described. Eight bibliographic control elements are defined, and the criteria for evaluating the occurrence of these elements in sixty-four sample catalogs are specified. When the distributors are grouped according to category, such as educational or commercial, the pattern of bibliographic control has three distinct clusters of elements. When the distributors are grouped by the number of titles handled, there is no clear pattern. The implications of these patterns are discussed in terms of practical library reference services. A solution to the problem of bibliographic control of health science audiovisual materials is proposed.

Audiovisual Aids↗

Searching MEDLINE free on the Internet using the National Library of Medicine's PubMed.

Searching MEDLINE, the National Library of Medicine's premier bibliographic database covering the fields of medicine, nursing, dental medicine, the healthcare system, veterinary medicine, and the preclinical sciences, is now available free on the Internet through PubMed. This retrieval system allows users of all skill levels to obtain important medical information. Additionally, through the National Network of Libraries of Medicine (NN/LM) program, a division of NLM, user support in the form of phone, e-mail, and training is available free of charge. Those interested in having a training session for PubMed at their facility may contact the NN/LM to make arrangements.

Computer User Training↗

Developing information-seeking skills in occupational therapy students.

This paper discusses the importance of teaching occupational therapy students methods for finding information in libraries. It details the efforts at Ohio State University to supply this instruction and demonstrates the positive results of library user education as seen by the instructors of occupational therapy students. This partnership between librarians and classroom instructors can easily be adapted to any health sciences education program.

Attitude of Health Personnel↗

Potent 2'-amino-2'-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor.

Screening of random oligonucleotide libraries with SELEX [systematic evolution of ligands by exponential enrichment; Tuerk, C., & Gold, L. (1990) Science 249, 505-510] has emerged as a powerful method for identifying high-affinity nucleic acid ligands for a wide range of molecular targets. Nuclease sensitivity of unmodified RNA and DNA, however, imposes considerable restrictions on their use as therapeutics or diagnostics. Modified RNA in which pyrimidine 2'-hydroxy groups have been substituted with 2'-amino groups (2'-aminopyrimidine RNA) is known to be substantially more resistant to serum nucleases. We report here on the use of SELEX to identify high-affinity 2'-aminopyrimidine RNA ligands to a potent angiogenic factor, basic fibroblast growth factor (bFGF). High-affinity ligands with the same consensus primary structure have been isolated from two independent libraries of approximately 6 x 10(14) molecules containing 30 or 50 randomized positions. Compared to unmodified RNA with the same sequence, 2'-aminopyrimidine ligands are at least 1000-fold more stable in 90% human serum. The sequence information required for high-affinity binding to bFGF is contained within 24-26 nucleotides. The minimal ligand m21A (5'-GGUGUGUGGAAGACAGCGGGUGGUUC-3'; G = guanosine, A = adenosine, C = 2'-amino-2'-deoxycytidine, U = 2'-amino-2'-deoxyuridine, and C = 2'-amino-2'-deoxycytidine or deoxycytidine) binds to bFGF with an apparent dissociation constant (Kd) of 3.5 +/- 0.3) x 10(-10) M at 37 degrees C in phosphate-buffered saline (pH 7.4). Disassociation of m21A from bFGF is adequately described with a first-order rate constant of (1.96 +/- 0.08) x 10(-3) s-1 (t1/2 = 5.9 min). The calculated value for the association rate constant (kon = k(off)/Kd) was 5.6 x 10(6) M-1 s-1. Highly specific binding of m21A to bFGF was observed: binding to denatured bFGF, five proteins from the FGF family (acidic FGF, FGF-4, FGF-5, FGF-6, and FGF-7), and four other heparin binding proteins is substantially weaker under the same conditions with KdbFGF/Kdprotein values ranging from (4.1 +/- 1.4) x 10(-2) to > 10(-6). Heparin but not chondroitin sulfate competed for binding of m21A to bFGF. In cell culture, m21A inhibited [125I]bFGF binding to both low-affinity sites (ED50 approximately 1 nM) and high-affinity sites (ED50 approximately 3 nM) on CHO cells expressing transfected FGF receptor-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The information age in concept and practice at the National Library of Medicine.

The evolution of today's information age is mirrored in the growth of the National Library of Medicine's bibliographic services: from the pioneering work of the Library in the last century to develop Index Medicus, to developing the innovative computerized MEDLARS system in the early 1960s, to the easily searchable on-line data bases now available to health professionals. The evolution has not come about without controversy, however, as tension developed between the public sector, where the information was viewed as a social benefit, and the private sector, where it was viewed as a source of profit. The Library has fostered research and development in biomedical communications in the laboratories of its Lister Hill Center and through grants to assist in establishing the field of medical informatics. The future of biomedical communications will be profoundly affected by work now being carried out by the Library: in fields such as biotechnology, through integrative methodologies such as the Unified Medical Language System now under development, and by a grant program to improve the infrastructure for information within academic health science centers.

Diffusion of Innovation↗