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PubMed2002

Generation of anti-colorectal cancer fab phage display libraries with a high percentage of diverse antigen-reactive clones.

A combinatorial Fab phage display library was generated from the antibody variable region genes of each of 2 BALB/c mice immunized with the human colorectal cancer cell lines SW480, SW948, and SW837. These libraries were shown to be diverse by nucleotide sequencing and diagnostic restriction enzyme digestion (fingerprinting) of individual members. The two libraries were combined and selected for binding to a suspension of formaldehyde-fixed human colorectal cancer cells in two successive rounds of selection and phage amplification by infection of bacteria. Analysis of the selected libraries as well as individual library clones by ELISA, showed binding to the cancer cell lines in both formaldehyde-fixed and native forms. Fifty five percent and 94% of library clones were positive for colorectal cancer cell binding after the first and second rounds of selection, respectively. Fingerprinting of individual clones showed the first round selected library to be very diverse and the second round selected library to be of more limited diversity. After absorption with normal human cell types, these anti-cancer selected libraries could be used to develop therapeutic and/or diagnostic agents.

Animals↗
PubMed2000

Providing health information to the general public: a survey of current practices in academic health sciences libraries.

A questionnaire was mailed to 148 publicly and privately supported academic health sciences libraries affiliated with Association of American Medical Colleges (AAMC-accredited medical schools in the United States and Canada to determine level of access and services provided to the general public. For purposes of this study, "general public" was defined as nonaffiliated students or health care professionals, attorneys and other nonhealth-related professionals, patients from affiliated or other hospitals or clinics, and general consumers. One hundred five (71%) libraries responded. Results showed 98% of publicly supported libraries and 88% of privately supported libraries provided access to some or all of the general public. Publicly supported libraries saw greater numbers of public patrons, often provided more services, and were more likely to circulate materials from their collections than were privately supported libraries. A significant number of academic health sciences libraries housed a collection of consumer-oriented materials and many provided some level of document delivery service, usually for a fee. Most allowed the public to use some or all library computers. Results of this study indicated that academic health sciences libraries played a significant role in serving the information-seeking public and suggested a need to develop written policies or guidelines covering the services that will be provided to minimize the impact of this service on primary clientele.

Community Participation↗
PubMed1995

Health sciences library building projects: 1994 survey.

Designing and building new or renovated space is time consuming and requires politically sensitive discussions concerning a number of both long-term and immediate planning issues. The Medical Library Association's fourth annual survey of library building projects identified ten health sciences libraries that are planning, expanding, or constructing new facilities. Two projects are in predesign stages, four represent new construction, and four involve renovations to existing libraries. The Texas Medical Association Library, the King Faisal Specialist Hospital and Research Centre Library, and the Northwestern University Galter Health Sciences Library illustrate how these libraries are being designed for the future and take into account areas of change produced by new information technologies, curricular trends, and new ways to deliver library services.

Chicago↗
PubMed1977

A college course for nurses on the utilization of library resources.

Library user instruction has been a no-man's-land between librarian and educator. Each assumes that the other has offered the student some necessary preparation before his assignments requiring library consultation. Too often, this is not the case. Reference librarians at the Duke University Medical Center Library are currently offering a ten-week, 1 1/2-hour credit library instruction course for nursing baccalaureate candidates. "Introduction to Library Resources in the Nursing Field" is designed not so much to orient students to a specific library facility, but rather, to provide them with background material on library organization and services and to familiarize them with basic bibliographic tools relevant to the nursing profession. Lectures are supplemented through the use of homework questions, bibliographies, handouts, in-class exercises, and on-line demonstrations. Very positive feedback from both students and faculty has attested to the value of such a course in the nursing curriculum and has resulted in its being offered four times to date. The library staff is exploring methods for offering additional library instruction not only to nursing students but to other user groups in Duke's medical complex.

Curriculum↗
PubMed2005

Library as place: results of a delphi study.

OBJECTIVE: An expert consensus on the future of the library as place was developed to assist health sciences librarians in designing new library spaces. METHOD: An expert panel of health sciences librarians, building consultants, architects, and information technologists was asked to reflect on the likelihood, desirability, timing, and impact on building design of more than seventy possible changes in the use of library space. RESULTS: An expert consensus predicted that the roles librarians play and the way libraries are used will substantially change. These changes come in response to changes in technology, scholarly communication, learning environments, and the health care economy. CONCLUSIONS: How health sciences library space is used will be far less consistent by 2015, as space becomes more tailored to institutional needs. However, the manner in which health sciences libraries develop and deliver services and collections will drastically change in the next decade. Libraries will continue to exist and will provide support for knowledge management and clinical trials, provide access to digital materials, and play a host of other roles that will enable libraries to emerge as institutional change agents.

Delphi Technique↗
PubMed1979

Cooperation strengthens small hospital libraries in a rural area of New England: a five-year experience.

Before 1970, library facilities and services at the small hospitals in rural Vermont were essentially nonexistent. Similar findings were later encountered along the Connecticut River in New Hampshire and in a small area of upstate New York. The Hospital Library Development Services program was established at the University of Vermont's Dana Medical Library to improve these conditions. Financial assistance was received from the National Library of Medicine, and by the end of 1974, thirty-three hospitals had staffed libraries. Earlier that year it has been decided to begin emphasing cooperation among the developing libraries, including the production of union lists and regular meetings of staff members from geographically proximate hospital libaries to plan and implement various activities. An additional one-year award from NLM was received in 1975. Results achieved during and after the period of grant support are reported. Cooperation among hospital libraries is seen as a feasible and beneficial undertaking provided that the participating libraries are internally supported and developing.

Financing, Government↗
PubMed1980

Consumer health information: libraries as partners.

The need for consumer health information delivery is becoming more evident to librarians. The results of a user survey at a large medical center library and a metropolitan public library confirm that the general public is making demands for health information at both types of libraries. Issues facing librarians are discussed; roles are suggested for public libraries, for academic health sciences libraries, and for hospital libraries. The importance of library involvement in the delivery of consumer health information is emphasized. Librarians are urged to define a role for themselves and to work hard at identifying the library profession to all others involved in the delivery of consumer health information.

Forecasting↗
PubMed1994

The Internet: will this highway serve the digital library?

The future of the biomedical enterprise and the biomedical libraries that serve it is tied closely to digital information. The changing nature of this type of information will create new pressures on libraries, particularly in health care organizations. Libraries must learn to deal with these pressures. Currently, libraries depend on the Internet primarily for connections to resources and other libraries; thus enhancements to the Internet will impact the libraries of the present and future significantly. This paper provides an overview of the technical capabilities that will be available in the near to midterm, what libraries will be able to do with those capabilities, and how libraries can position themselves to take advantage of the impending changes.

Computer Communication Networks↗
PubMed1994

A survey of patient access to hospital and medical school libraries.

The American Medical Association (AMA) Library and Information Management Division conducted a survey of 481 randomly selected hospital and medical center libraries. Data were obtained from 307 libraries (63.8%). The tabulated results showed that 58.1% of responding libraries allow patient access without restrictions. Another 19.9% allow patient access with restrictions, such as physician approval (13.4%) or various other limitations (6.5%). Many of the surveyed librarians (67%) said their institutions have separate nontechnical libraries for patients. Medical library access was strongly or somewhat supported by 89.6% of the respondents; 6.1% were somewhat opposed, and 4.3% were strongly opposed to patient access. Approximately 10% of the libraries surveyed provided no patient education forum. The AMA trustees used the results of the survey in deciding whether to encourage hospitals and medical schools to make their libraries accessible for use by patients and their families.

Libraries, Hospital↗
PubMed1996

The role of the medical departmental library.

At most academic medical institutions, the first level of library service is provided by health sciences or medical school libraries. For many medical departments, however, these services are also provided by a second-level library, the departmental library. These libraries are usually supported by a specific department, such as surgery, and provide customized services to this sponsor. Departmental libraries continue to play an important role amid the debate over centralized, versus decentralized, library systems. On the basis of a limited survey, this paper describes a representative medical departmental library.

Canada↗
PubMed1995

Three region-specific microdissection libraries for the long arm of human chromosome 2, regions q33-q35, q31-q32, and q23-q24.

Three region-specific libraries have been constructed from the long arm of human chromosome 2, including regions 2q33-35 (2Q2 library), 2q31-32 (2Q3) and 2q23-24 (2Q4). Chromosome microdissection and the MboI linker-adaptor microcloning techniques were used in constructing these libraries. The libraries comprised hundreds of thousands of microclones in each library. Approximately half of the microclones in the library contained unique or low-copy number sequence inserts. The insert sizes ranged between 50 and 800 bp, with a mean of 130-190 bp. Southern blot analysis of individual unique sequence microclones showed that 70-94% of the microclones were derived from the dissected region. 31 unique sequence microclones from the 2Q2 library, 31 from 2Q3, and 30 from 2Q4, were analyzed for insert sizes, the hybridizing genomic HindIII fragment sizes, and cross-hybridization to rodent species. These libraries and the short insert microclones derived from the libraries should be useful for high resolution physical mapping, sequence-ready reagents for large scale genomic sequencing, and positional cloning of disease-related genes assigned to these regions, e.g. the recessive familial amyotrophic lateral sclerosis assigned to 2q33-q35, and a type I diabetes susceptibility gene to 2q31-q33.

Amyotrophic Lateral Sclerosis↗
PubMedDate not supplied

A statistical-based approach to assessing the fidelity of combinatorial libraries encoded with electrophoric molecular tags. Development and application of tag decode-assisted single bead LC/MS analysis.

A statistical sampling protocol is described to assess the fidelity of libraries encoded with molecular tags. The methodology, termed library QA, is based on the combined application of tag decode analysis and single bead LC/MS. The physical existence of library compounds eluted from beads is established by comparing the molecular weight predicted by tag decode with empirical measurement. The goal of sampling is to provide information on overall library fidelity and an indication of the performance of individual library synthons. The minimal sampling size n for library QA is l0 x the largest synthon set. Data are reported as proportion (p) +/- lower and upper boundary (lb-ub) computed at the 95% confidence level (alpha = 0.05). As a practical demonstration, library QA was performed on a 25,200-member library of statine amides (size = 40 x 63 x 10). Sampling was conducted three times at n approximately 630 beads per run for a total of 1902 beads. The overall proportions found for the three runs were consistent with one another: p = 84.4%, lb-ub = 81.5-87.2%; p = 83.1%, lb-ub = 80.2-85.95; and p = 84.5%, lb-ub = 81.8-87.3%, suggesting the true value of p is close to 84% compound confirmation. The performance pi of individual synthons was also computed. Corroboration of QA data with biological screening results obtained from assaying the library against cathepsin D and plasmepsin II is discussed.

Journal Article↗
PubMedDate not supplied

Generalization of a targeted library design protocol: application to 5-HT7 receptor ligands.

Herein a general concept for the design of targeted libraries for proteins with binding sites that are divided into subsites is laid out, including several practical aspects and their solutions. The design is based on a chemogenomic classification of the subsites followed by collection of bioactive molecular fragments and virtual library generation. The general process is outlined and applied to the assembly of a library of 500 molecules targeting the serotonin type 7 (5-HT7) receptor, a class A G-Protein Coupled Receptor (GPCR). Utilizing commercially available building blocks of similar size and composition, a reference library was created. Control sets of known ligands for the 5-HT7 receptor, other GPCRs, and nuclear receptors were collected from literature sources. Principal component analysis of molecular descriptors for the two libraries and the literature sets, displayed a focusing of the targeted library to the region in the chemical space defined by the literature actives, suggesting a denser coverage of the bioactive region than for the more diverse reference library. Additional computational validations, including PCA class predictions, 3D pharmacophore modeling, and docking calculations all indicated an enrichment factor of 5-HT7 ligand-like molecules in the range of 2-4 for the targeted library compared to the reference library.

Binding Sites↗
PubMed1995

Inhibitors of human heart chymase based on a peptide library.

We have synthesized two sets of noncleavable peptide-inhibitor libraries to map the S and S' subsites of human heart chymase. Human heart chymase is a chymotrypsin-like enzyme that converts angiotensin I to angiotensin II. The first library consists of peptides with 3-fluorobenzylpyruvamides in the P1 position. (Amino acid residues of substrates numbered P1, P2, etc., are toward the N-terminal direction, and P'1, P'2, etc., are toward the C-terminal direction from the scissile bond.) The P'1 and P'2 positions were varied to contain each one of the 20 naturally occurring amino acids and P'3 was kept constant as an arginine. The second library consists of peptides with phenylalanine keto-amides at P1, glycine in P'1, and benzyloxycarbonyl (Z)-isoleucine in P4. The P2 and P3 positions were varied to contain each of the naturally occurring amino acids, except for cysteine and methionine. The peptides of both libraries are attached to a solid support (pins). The peptides are evaluated by immersing the pins in a solution of the target enzyme and evaluating the amount of enzyme absorbed. The pins with the best inhibitors will absorb most enzyme. The libraries select the best and worst inhibitors within each group of peptides and provide an approximate ranking of the remaining peptides according to Ki. Through this library, we determined that Z-Ile-Glu-Pro-Phe-CO2Me and (F)-Phe-CO-Glu-Asp-ArgOMe should be the best inhibitors of chymase in this collection of peptide inhibitors. We synthesized the peptides and found Ki values were 1 nM and 1 microM, respectively. The corresponding Ki values for chymotrypsin were 10 nM and 100 microM. The use of libraries of inhibitors has advantages over the classical method of synthesis of potential inhibitors in solution: the libraries are reusable, the same libraries can be used with a variety of different serine proteases, and the method allows the screening of hundreds of compounds in short periods of time.

Amino Acid Sequence↗
PubMed2002

Statistical evaluation of SAGE libraries: consequences for experimental design.

Since the introduction of serial analysis of gene expression (SAGE) as a method to quantitatively analyze the differential expression of genes, several statistical tests have been published for the pairwise comparison of SAGE libraries. Testing the difference between the number of specific tags found in two SAGE libraries is hampered by the fact that each SAGE library is only one measurement: the necessary information on biological variation or experimental precision is not available. In the currently available tests, a measure of this variance is obtained from simulation or based on the properties of the tag distribution. To help the user of SAGE to decide between these tests, five different pairwise tests have been compared by determining the critical values, that is, the lowest number of tags that, given an observed number of tags in one library, needs to be found in the other library to result in a significant P value. The five tests included in this comparison are SAGE300, the tests described by Madden et al. (Oncogene 15: 1079-1085, 1997) and by Audic and Claverie (Genome Res 7: 986-995, 1997), Fisher's Exact test, and the Z test, which is equivalent to the chi-squared test. The comparison showed that, for SAGE libraries of equal as well as different size, SAGE300, Fisher's Exact test, Z test, and the Audic and Claverie test have critical values within 1.5% of each other. This indicates that these four tests will give essentially the same results when applied to SAGE libraries. The Madden test, which can only be used for libraries of similar size, is, with 25% higher critical values, more conservative, probably because the variance measure in its test statistic is not appropriate for hypothesis testing. The consequences for the choice of SAGE library sizes are discussed.

Databases, Genetic↗
PubMed1986

Molecular characterization of the purity of seven human chromosome-specific DNA libraries.

We have characterized at the molecular level seven chromosome-specific libraries constructed in phage lambda Charon 21A from flow-sorted human chromosomes. The purity of libraries prepared from chromosomes sorted from hamster X human cells was estimated by species-specific hybridization and ranged from 48% to 83% of clones containing human inserts. Among libraries of chromosomes from human cells, mass screenings were made for repetitive sequences and 20 clones from the #18 and #20 libraries were analyzed in detail. Ten to fifteen percent of all clones contain sequences which can be mapped; 80-100% of these derive from the intended chromosome of origin, demonstrating very high purity and a 35 X enrichment of chromosome-specific sequences over a total genomic library. The two libraries contain a high, though dissimilar, percent of repeat-containing clones; the #18 library has 55% repetitive clones and the #20 library 85%. This dissimilarity may be due to a difference in insert size distribution, since the #18 library has smaller inserts than the #20. This could be caused by variation in extent of digestion of insert DNA and/or differences in sequence organization between the two chromosomes. A method more sensitive than conventional plaque-lift screening was used to detect repetitive inserts; in this way nearly all repetitive clones could be eliminated before purification of their DNAs.

Animals↗
PubMed2004

Using GIS to establish a public library consumer health collection.

BACKGROUND: Learning the exact demographic characteristics of a neighborhood in which a public library serves, assists the collection development librarian in building an appropriate collection. Gathering that demographic information can be a lengthy process, and then formatting the information for the neighborhood in question becomes arduous.As society ages and the methods for health care evolve, people may take charge of their own health. With this prospectus, public libraries should consider creating a consumer health collection to assist the public in their health care needs. Using neighborhood demographic information can inform the collection development librarians as to the dominant age groups, sex, and races within the neighborhood. With this information, appropriate consumer health materials may be assembled in the public library. METHODS: In order to visualize the demographics of a neighborhood, the computer program ArcView GIS (geographic information systems) was used to create maps for specified areas. The neighborhood data was taken from the U.S. Census Department's annual census and library addresses were accumulated through a free database. After downloading the census block information from http://www.census.gov/geo/www/tiger/ the data was manipulated with ArcView GIS and queried to produce maps displaying the requested neighborhood demographics to view in respect to libraries. RESULTS: ArcView GIS produced maps displaying public libraries and requested demographics. After viewing the maps the collection development librarian can see exactly what populations are served by the library and adjust the library's collection accordingly. CONCLUSIONS: ArcView GIS can be used to produce maps displaying the communities that libraries serve, spot boundaries, be it "man-made or natural," that exist prohibiting customer service, and assist collection development librarians in justifying their purchases for a dedicated consumer health collection or resources in general.

Journal Article↗
PubMed2002

A multigeneration analysis of cytochrome b(562) redox variants: evolutionary strategies for modulating redox potential revealed using a library approach.

The redox potential of cytochromes sets the energy yield possible in metabolism and is also a key determinant of the rate at which redox reactions proceed. Here, the heme protein, cytochrome b(562), is used to study the in vitro evolution of redox potential within a library of variants containing the same structural archetype, the four-helix bundle. Multisite variations in the active site of cytochrome b(562) were introduced. A library of variants containing random mutations in place of R98 and R106 was created, and the redox potentials of a statistical sampling of this library were measured. This procedure was carried out for both the low- and high-potential variants of a previously studied F61X/F65X, first-generation library [Springs, S. L., Bass, S. E., and McLendon, G. L. (2000) Biochemistry 39, 6075]. The second-generation library reported here has a range of redox potentials which is greater than 40% (160 mV) of the known accessible potential among cytochromes with identical axial ligands (but different folds) and exceeds the range exhibited phylogenetically by the cytochrome c' family which internally maintains the same axial ligation and fold. A statistical analysis of the libraries examined reveals that the redox potential of WT cyt b(562) is found at the high-potential extremum of the distribution, indicating that this protein apparently evolved to differentially stabilize the reduced protein. The 2.7 A crystal structure of F61I/F65Y/R106L (low-potential variant of the second-generation library) was solved and is compared to the wild-type structure and the 2.2 A resolution structure of the F61I/F65Y variant (low-potential variant of the first-generation library). The structures indicate that charge-dipole effects are responsible for shifting the redox equilibrium toward the oxidized state in both the F61I/F65Y and F61I/F65Y/R106L variants. Specifically, a new protein dipole is introduced into the heme microenvironment as a result of the F65Y mutation, two new internal water molecules (one in hydrogen-bonding distance of Y65) are found, and in the case of F61I/F65Y/R106L (DeltaE(m) = 158 mV vs NHE), increased solvent exposure of the heme as a result of the R106L substitution is identified.

Binding Sites↗