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At least 145 records · Page 8Linked to original sources

Construction of a family of biphenyl combinatorial libraries: structure-activity studies utilizing libraries of mixtures.

A set of biphenyl aminoacid building blocks has been synthesized. These were used to construct partially-peptidic combinatorial libraries as equimolar multi-component samples. Activity of members of this library as vitronectin receptor antagonists is described, together with SAR studies of the most active members. These studies illustrate several important features of combinatorial libraries.

Biphenyl Compounds↗

Solution-phase synthesis of a 1,5-dialkylamino-2,4-dinitrobenzene library and the identification of novel antibacterial compounds from this library.

In this report we demonstrate that a 1,5-dialkylamino-2,4-dinitrobenzene small molecule library can be generated by a highly efficient solution-phase synthesis method. From this 2485-member library, a series of novel compounds with antibacterial activity were isolated. The significance of this report is that the synthetic scheme is extremely simple, with minimal number of liquid handling steps, and the solvents and reagents left in the final library preparation are fully compatible with cell-based assays.

Anti-Bacterial Agents↗

Microwave parallel library generation: comparison of a conventional- and microwave-generated substituted 4(5)-sulfanyl-1H-imidazole library.

A methodology for the microwave parallel synthesis of libraries is described. The procedure involves the use of an array of expandable reaction vessels, which can accommodate pressure buildup within the vessel due to heating without loss of volatile solvents or reagents. A demonstration 24-membered library of substituted 4(5)-sulfanyl-1H-imidazoles was generated by both conventional and microwave procedures, achieving a reduction from 12 h to 16 min in library generation time for the microwave approach.

Combinatorial Chemistry Techniques↗

PCR-based cDNA library construction: general cDNA libraries at the level of a few cells.

A procedure for the construction of general cDNA libraries is described which is based on the amplification of total cDNA in vitro. The first cDNA strand is synthesized from total RNA using an oligo(dT)-containing primer. After oligo(dG) tailing the total cDNA is amplified by PCR using two primers complementary to oligo(dA) and oligo(dG) ends of the cDNA. For insertion of the cDNA into a vector a controlled trimming of the 3' ends of the cDNA by Klenow enzyme was used. Starting from 10 J558L micron3 myeloma cells, total cDNA was synthesized and amplified approximately 10(5) fold. A library containing 10(6) clones was established from 1/6 of the amplified cDNA. Screening of the library with probes for three genes expressed in these cells revealed a number of corresponding clones in each case. The longest obtained clones contained inserts of 1.5 kb length. No sequences originating from carriers or from rRNA was found in 14 randomly picked clones.

Cloning, Molecular↗

National library of medicine regional medical library program.

The National Library of Medicine is charged with the development and management of a National Biomedical Communications Network. The Regional Medical Library Program is a forerunner of such a network; the product and institutions involved will be critical elements in its evolution. The immediate objective of the RMLP, the facilitation of biomedical information transfer, presents a logistical problem requiring substantial commitment from the health sciences community and extensive cooperation among libraries in each region.

Journal Article↗

Recommendations for responsible monitoring and regulation of clinical software systems. American Medical Informatics Association, Computer-based Patient Record Institute, Medical Library Association, Association of Academic Health Science Libraries, American Health Information Management Association, American Nurses Association.

In mid-1996, the FDA called for discussions on regulation of clinical software programs as medical devices. In response, a consortium of organizations dedicated to improving health care through information technology has developed recommendations for the responsible regulation and monitoring of clinical software systems by users, vendors, and regulatory agencies. Organizations assisting in development of recommendations, or endorsing the consortium position include the American Medical Informatics Association, the Computer-based Patient Record Institute, the Medical Library Association, the Association of Academic Health Sciences Libraries, the American Health Information Management Association, the American Nurses Association, the Center for Healthcare Information Management, and the American College of Physicians. The consortium proposes four categories of clinical system risks and four classes of measured monitoring and regulatory actions that can be applied strategically based on the level of risk in a given setting. The consortium recommends local oversight of clinical software systems, and adoption by healthcare information system developers of a code of good business practices. Budgetary and other constraints limit the type and number of systems that the FDA can regulate effectively. FDA regulation should exempt most clinical software systems and focus on those systems posing highest clinical risk, with limited opportunities for competent human intervention.

Clinical Medicine↗

Powerful connections for public health: the National Library of Medicine and the National Network of Libraries of Medicine.

As incorporated in Healthy People 2010 objectives, data and information systems and a skilled workforce are 2 of the critical components of the public health infrastructure. The National Library of Medicine (NLM) and the National Network of Libraries of Medicine (NN/LM) are important resources for improving Internet access and providing related training to the public health workforce and to those in training for public health careers. The NLM and the NN/LM have joined forces with the Centers for Disease Control and Prevention, the Health Resources and Services Administration, the Association of State and Territorial Health Officials, the National Association of County and City Health Officials, and the Public Health Foundation. The goal of this collaboration is to improve electronic resources useful in public health practice and increase awareness of them, to train public health professionals to use electronic information services, and to help public health agencies obtain the equipment and Internet connections needed to use these services effectively. The databases, outreach programs, and connection grants available to public health professionals from the NLM, and the training and ongoing support available from the NN/LM for accessing these programs and services, are described.

Centers for Disease Control and Prevention, U.S.↗

Mechanization of library procedures in the medium-sized medical library. IV. Physical characteristics of the acquisitions-cataloging record.

Acquisitions-Cataloging records stored on magnetic tape by the Washington University School of Medicine Library were examined to determine frequency and average length of record components and their alphabetization requirements in a book catalog. Data from this study of 4,708 records will be used in adaptation of the Library's computer-based cataloging system to greater machine capabilities. The first of these two papers compares measurements found for WUSML records with those reported in studies of conventional catalog cards. The number of sorting positions used to alphabetize entries and causes of sort failure are examined in the second paper (Number V) which will be found on page 71 of this issue of the BULLETIN.

Cataloging↗

Automation of internal library operations in academic health sciences libraries: a state of the art report.

A survey of automated records management in the United States and Canada was developed to identify existing on-line library systems and technical expertise. Follow-up interviews were conducted with ten libraries. Tables compare the features and availability of four main frame and four minicomputer systems. Results showed: a trend toward vendor-supplied systems; little coordination of efforts among schools; current system developments generally on a universitywide basis; and the importance of having the cooperation of campus computer facilities to the success of automation efforts.

Automation↗

Descriptive cataloging of serials: the National Library of Medicine versus the Library of Congress.

Descriptive cataloging practices for serial differ significantly in some respects between the Library of Congress and the National Library of Medicine. This paper compares some of these differences and indicates the impact they can have on the development of on-line cooperative data bases such as OCLC. Attention is also given to the possible impact of the second edition of the Anglo-American Cataloguing Rules on serials cataloging. The need for standardization is stressed.

Cataloging↗

Planning for meaningful change in libraries and library networks: a first step.

The Program Planning Model (PPM) is a planning and management tool that facilitates development and acceptance of significant programs. PPM assists program planning by systematically involving consumer or user groups in the development and review of new programs. While user participitation is important throughout PPM, this involvement is especially important during the problem exploration phase, when the problems or needs of these users are surveyed. The Nominal Group Technique (NGT), a variation of the "brainstorming" process, is a structured but flexible group process used in the problem exploration phase to generate a high number of useful responses concerning problem areas. NGT ensures maximum contribution of ideas by all participtants. NGT and its application in the planning and management efforts of several libraries and library networks are described in detail.

Group Processes↗

The Galter Health Sciences Library at Northwestern University: a library for the 21st century.

Initiated to increase space, renovation planning for Northwestern University's Galter Health Sciences Library evolved into a process for developing a more technology-centered library. Design focused on correcting structural problems and providing greater access to technology. Space was redesigned for functionality and flexibility. Design features included a new entrance, relocated and expanded learning resource center; certain limitations remained. The planning process involved all major groups on campus; construction will be phased.

Facility Design and Construction↗

Sorting polyclonal antibodies into functionally distinct fractions using peptide phage display: 'a library on top of a library'.

A general approach for sorting antibodies (Abs) to a restricted protein domain was developed using phage-displayed peptide libraries. The method is demonstrated by fractionating polyclonal antibodies (pAbs), raised against a short peptide derived from the extracellular, juxtamembrane region of fibroblast growth factor receptor 1 (FGFR1) into fractions with distinct chemical and biological characteristics. Screening two combinatorial peptide libraries, with the pAb, several sequences, homologous to different regions within the original peptide, were identified. Four of the corresponding peptides were synthesized and used as peptide-conjugated affinity columns for the fractionation of the pAbs. The fractions obtained were unique in their recognition patterns and in their capacity to immunoprecipitate and immunoblot, as well as to modulate the activity of FGFR1. This technique is, therefore, highly sufficient in separating pAbs to monospecific fractions and may also be used for fine mapping of different, even overlapping, sequences within a restricted peptide or protein domain.

Amino Acid Sequence↗

Panning of a phage VH library using nitrocellulose membranes: application to selection of a human VH library.

We have established a method for selecting binding phages from a phage immunoglobulin heavy chain variable region (VH) library by panning with nitrocellulose membranes (membrane panning). To evaluate the concentrating ability of membrane panning for binding phages, a phage VH library containing clones that bind to hen egg white lysozyme (HEL) was used for panning against HEL. The efficiency of our method was as high as that of panning with magnetic beads. In addition, we performed membrane panning against target proteins and isolated the binding phages. The human VH genes of these phages were cloned and expressed as VH-bacterial alkaline phosphatase (PhoA) conjugates (VH-PhoA) in Escherichia coli. The dose-dependent binding of VH-PhoA to target proteins was confirmed by dot blotting. When applied to disease-associated antibodies, these methods will likely benefit clinical research. In addition, these techniques may be applicable to systematic analysis in proteome studies.

Alkaline Phosphatase↗

Construction of human naïve Fab library and characterization of anti-met Fab fragment generated from the library.

Inappropriate expression of the receptor tyrosine kinase Met and its ligand hepatocyte growth factor (HGF)/scatter factor (SF) is usually associated with an aggressive solid tumor phenotype (angiogenesis, invasiveness, and metastasis) and poor clinical prognosis. We report here the design and construction of a large, human naïve antigen-binding fragment (Fab) phage-display library with a diversity of 2.0 x 109, which allows rapid isolation of antigen-specific human antibody fragments. A Fab fragment specifically against Met (designated hFab-Met-1) was successively selected from this library by using biopanning on Met-transfected cell line S114. The specificity of hFab-Met-1 was characterized by immunoprecipitation, Western blotting, and flow cytometry. The results demonstrate that hFab-Met-1 reacts with the extracellular domain of Met in its native conformation. Moreover, functional analysis by Madine-Darby canine kidney cell scattering and urokinase-type plasminogen activator assays demonstrated that hFab-Met-1 is not an agonist to HGF/Met signaling compared with a murine intact monoclonal antibody (MAb) Met5. To confirm that hFab-Met-1 interacts with Met-expressing tumors in vivo, I-125-labeled hFab-Met-1 was nuclear-imaged in a mouse xenograft of Met- and HGF/SF-expressing human leiomyosarcoma. Total body scintigrams were obtained between 1 and 48 h postinjection (PI). Tumor-associated activity was imaged as early as 1 h PI, and remained visible in some animals as late as 24 h PI. As expected, activity was highest in the kidneys in early images, whereas thyroid activity became predominant in later images. In conclusion, hFab-Met-1 interacts with Met both in vitro and in vivo, and is a promising candidate for clinical diagnosis and therapeutics.

Animals↗