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PubMed1992

The value of systematic reading. Retaining and applying current information is vital in developing leadership ability.

Keeping up-to-date, having the right information, and growing in knowledge and awareness are more important than ever. Reading is one of the primary ways to develop professional expertise and leadership ability--and to stay competitive. Many persons are facing the new reality: Job security is an inner factor based on inner competence. Part of that competence has to do with one's ability and skill in continually learning. People who read not only develop more competence in their current abilities but, equally important, develop confidence in their ability to learn and meet the demands of accelerated change. Reading helps people stay up-to-date and broaden their perspectives. Reading also provides enjoyment. But if we do not remember and apply what we read, it has little value. People therefore must read widely and read deliberately for retention and application. To make reading a part of their lives, people must make a commitment to read every day, read material that interests them, visit bookstores and libraries, work at retention and application, discuss with others what they are reading, and test what they read against their own experience.

Administrative Personnel↗
PubMed1987

Beyond the online catalog: developing an academic information system in the sciences.

The online public access catalog consists essentially of a machine-readable database with network capabilities. Like other computer-based information systems, it may be continuously enhanced by the addition of new capabilities and databases. It may also become a gateway to other information networks. This paper reports the evolution of the Bibliographic Access and Control System (BACS) of Washington University in end-user searching, current awareness services, information management, and administrative functions. Ongoing research and development and the future of the online catalog are also discussed.

Catalogs, Library↗
PubMed1980

The effect of inflation on the cost of journals on the Brandon list.

A study of the increases over the past twenty years in the cost of the journals included in the 1977 Brandon list was conducted. This information is compared to the general U.S. rate of inflation for the same period as represented by the consumer price index. Results indicate that the Brandon list journal's prices have been increasing at a significantly higher rate than the general rate of inflation for this period. This information should be useful to the hospital librarian who must justify to administrators the need for increased funding beyond the general rate of inflation.

Costs and Cost Analysis↗
PubMed2006

Serial analysis of gene expression in the rat striatum following methamphetamine administration.

Methamphetamine (METH), a highly addictive drug, can cause degeneration of monoaminergic terminals and neuronal apoptosis in the mammalian brain. In the present article, we have used serial analysis of gene expression (SAGE) to investigate patterns of gene expression in the striata of rats that were given a neurotoxic dose of the drug. SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO(2) homeostasis.

Animals↗
PubMed1972

The acute effect of ethanol on albumin, fibrinogen and transferrin synthesis in the rat.

Decrease of absolute synthesis of albumin and fractional synthesis of transferrin was observed within 3h of orally administering ethanol (4ml/kg) to rats maintained on a 40%-protein diet. In contrast, absolute synthesis of fibrinogen was unaffected. With this ethanol intake, the changes in protein synthesis occurred without significant ultrastructural change in the liver. When the ethanol intake was greater (8ml/kg) ultrastructural disruption was observed. However, both the decrease of plasma protein synthesis and the ultrastructural alterations could be prevented by the simultaneous administration of a mixture of amino acids with the ethanol. The latter findings, not reported hitherto, suggest that ethanol may interfere with hepatic plasma protein synthesis and ultrastructure more through a disturbance of amino acid metabolism than through direct physical damage to the hepatocyte. An Appendix outlines the deconvolutional method used to correct for losses of labelled protein in the period during which measurements were made. The principle may also be applied to labelled plasma urea. The details of the calculations are given in a supplementary paper that has been deposited as Supplementary Publication 50007 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1972) 126, 5.

Administration, Oral↗
PubMed1989

Kallikrein-related protease in the rat ventral prostate: cDNA cloning and androgen regulation.

A kallikrein-related protease was purified from rat ventral prostate cytosol by means of DEAE-Sepharose chromatography, followed by gel filtration on Sephadex G-100 and CM-cellulose chromatography. Antibodies raised in rabbits against the purified protease recognize two bands on immunoblots of prostatic cytosol: a 31,000 Da band and an 18,000 Da band, which constitutes a proteolytic breakdown product of the former. The corresponding cDNA was isolated from a prostatic cDNA library, inserted in a lambda gt11 vector, using immunodetection for screening and identified as encoding a kallikrein- and tonin-related protease. Castration resulted in a marked decrease of the level of the protease and its mRNA, whereas administration of androgens to castrated animals resulted in marked stimulation. These data support the hypothesis that this protease is a member of a cluster of proteins, that are regulated in parallel by androgens in prostatic epithelial cells.

Amino Acid Sequence↗
PubMed2006

Amelioration of amyloid load by anti-Abeta single-chain antibody in Alzheimer mouse model.

Parenteral immunization of transgenic mouse models of Alzheimer disease (AD) with synthetic amyloid beta-peptide (Abeta) prevented or reduced Abeta deposits and attenuated their memory and learning deficits. A clinical trial of immunization with synthetic Abeta, however, was halted due to brain inflammation, presumably induced by a toxic Abeta, T-cell- and/or Fc-mediated immune response. Another issue relating to such immunizations is that some AD patients may not be able to raise an adequate immune response to Abeta vaccination due to immunological tolerance or age-associated decline. Because peripheral administration of antibodies against Abeta also induced clearance of amyloid plaques in the model mice, injection of humanized Abeta antibodies has been proposed as a possible therapy for AD. By screening a human single-chain antibody (scFv) library for Abeta immunoreactivity, we have isolated a scFv that specifically reacts with oligomeric Abeta as well as amyloid plaques in the brain. The scFv inhibited Abeta amyloid fibril formation and Abeta-mediated cytotoxicity in vitro. We have tested the efficacy of the human scFv in a mouse model of AD (Tg2576 mice). Relative to control mice, injections of the scFv into the brain of Tg2576 mice reduced Abeta deposits. Because scFvs lack the Fc portion of the immunoglobulin molecule, human scFvs against Abeta may be useful to treat AD patients without eliciting brain inflammation.

Alzheimer Disease↗
PubMed2004

A role of anti-verotoxin antibody immunoreactive peptide, Virp5, from rat spinal cord.

An anti-verotoxin 2 (VT2) antibody immunoreactive 5-kDa polypeptide (Virp5), has been obtained through screening of the rat spinal cord cDNA library with the aid of anti-VT2 antibody. Virp5 was mainly expressed in the central nervous system, liver and kidney, and localized at glia-like cells and nerve fibers in the central nervous system, vascular endothelial cells and hepatic cells in the liver, as well as epithelial cells of distal tubules in the kidney. Intravenous administration of purified Virp5 elicited a dose-dependent increase in blood pressure. These results suggest that Virp5 commonly exists in the body, being partly playing a role in regulating the blood pressure.

Amino Acid Sequence↗
PubMed2002

Effect of a peroxisome proliferator on 3 beta-hydroxysteroid dehydrogenase.

To better understand the changes that occur following exposure to peroxisome proliferators, we utilized mRNA differential display and microarray to screen for peroxisome proliferator target genes apart from those involved in lipid metabolism in male C57B6 mice by using the ubiquitous plasticizer, di(2-ethylhexyl)phthalate (DEHP). One noted change was the dose-dependent suppression of the mouse hormone metabolizing 3 beta-hydroxysteroid dehydrogenase V (HSD3b5), which is specifically expressed in the male mouse liver. Northern analysis showed that HSD3b5 mRNA levels decreased dramatically upon one-day exposure to 2.0% dietary DEHP, and were nearly undetectable by one week of treatment. Food restriction also significantly suppressed HSD3b5 expression; however, in this case the suppression was delayed and to a lesser extent. Another mouse 3 beta-hydroxysteroid dehydrogenase, HSD3b4, predominantly expressed in kidneys, was also regulated by DEHP and food restriction. The sex-specific gene, HSD3b5, was affected more by DEHP and food restriction than the tissue-specific gene, HSD3b4.

3-Hydroxysteroid Dehydrogenases↗
PubMed2005

Collaboration in support of curricular innovations.

The migration of traditional anatomy and pathology wet labs to a digital format requires significant planning and collaboration amongst key faculty, administrative, and technology personnel. In addition to conversion of course materials, the changed format necessitated the refurbishment of a traditional bench lab as a state-of-the art digital classroom, significant IT investment, and ongoing coordination by library, classroom and computer resources personnel. Standardized policies and procedures were developed to guide additional requests for software to support new educational initiatives.

Anatomy↗
PubMed2004

A nicotine delivery device without the nicotine? Tobacco industry development of low nicotine cigarettes.

BACKGROUND: Defining harm reduction and regulating potentially reduced exposure products (PREPs), including low nicotine products, are key issues in tobacco control policy. The US Congress has been considering legislation authorising the Food and Drug Administration (FDA) to regulate tobacco products. OBJECTIVE: To investigate tobacco industry perceptions, interests, motivations, and knowledge regarding the marketability of low nicotine tobacco products. METHODS: Qualitative analysis of internal tobacco industry documents identified in the Legacy Tobacco Documents Library between February 2002 and June 2004. Search terms included low-, no-, reduced-nicotine; denicotinization; low-, reduced- alkaloids; Next; de-nic; and key names of people, organisations, projects, and their common abbreviations and acronyms. RESULTS: The tobacco industry has made repeated efforts to develop low nicotine cigarettes. Reasons for doing so include consumer appeal and economic importance in a highly competitive cigarette market for "healthier" products. The industry considered the development of a new "denic" market segment a critical challenge. CONCLUSIONS: The tobacco industry exploits consumer misunderstanding of the health effects of nicotine in development and marketing efforts. The industry has risked the development of a less addictive product to expand the market reach of tobacco products based on perceived health benefits and appeal to quitters.

Alkaloids↗
PubMed1997

Neurological effects associated with use of the insect repellent N,N-diethyl-m-toluamide (DEET).

BACKGROUND: N,N-Diethyl-m-toluamide, an effective tick repellent, when applied to the skin, is the major component of essentially all of the products marketed for this purpose. It is used by about 30% of the US population, and by 23-29% of children in this population. Reports of neurologic adversity and death are rare and primarily involve children, but the dose relationship between N,N-diethyl-m-toluamide exposure and the symptoms reported in the clinical literature is difficult to establish. METHODS: Animal toxicology studies, clinical reports of neurological adversities in children and adults, and the available Poison Control Center records have been reviewed in an effort to understand the relationship between the N,N-diethyl-m-toluamide exposure and reported adverse events. CONCLUSIONS: Based on (1) the animal toxicology database on N,N-diethyl-m-toluamide, (2) the reports of adverse events in humans, and (3) the possible alternate etiologies for the symptoms reported in most patients, the risk of adversity from label-directed use of N,N-diethyl-m-toluamide appears low. Future efforts should focus on the prospective collection of adversity data with special attention paid to the documentation of clinical effects.

Administration, Cutaneous↗
PubMed2004

Development of gene therapy to target pancreatic cancer.

Pancreatic cancer remains one of the most difficult cancers to treat. Its high propensity to infiltrate and metastasize early from a small primary focus necessitates development of a new therapy which can track down the disseminated cancer cells in vivo. Gene therapy may offer new opportunities for a variety of targeting strategies, and we review here some of our work related to the development of targeted gene therapy: 1) Targeting by specific molecular abnormality: Many pancreatic cancer cells show "addiction" to K-ras mutation, while normal cells appear resistant to suppression of K-ras-mediated signaling by antisense K-ras RNA expression adenoviral vector. 2) Targeting by in vivo tumor characteristics: In a peritoneal dissemination model, intraperitoneal lipofection/polyfection can deliver and express transgenes highly preferentially in tumor nodules. 3) Targeting by vector: An efficient protocol for construction of an adenovirus expression vector library has been developed, which will enable a direct functional selection of fiber knob-modified targeting vector species for given cells. 4) Targeting by tumor immunity: Several cytokines not only induce direct cytotoxicity, but are also expected to activate specific immunity to achieve targeted suppression of cancer cells in vivo. Unlike parenteral administration of short-lived recombinant interferon protein, local interferon gene transfer can provide a target tissue-restricted distribution and sustained expression, which may improve the efficacy/safety balance of cytokine therapy. Cancer gene therapy development is, in general, at the stage of proof of principles and safety. However, it is an art of integrated science. The recent rapid progress of related sciences and technologies will expand the potential and consolidate the clinical reality of gene therapy.

Adenocarcinoma↗
PubMed2002

TA-19, a novel protein antigen of Trichosporon asahii, in summer-type hypersensitivity pneumonitis.

The most common form of hypersensitivity pneumonitis in Japan is summer-type hypersensitivity pneumonitis (SHP), which is caused by the inhalation of Trichosporon asahii or Trichosporon mucoides. To seek protein antigens relevant to the immunopathogenesis of SHP, we constructed a cDNA expression library of T. asahii, a major causative yeast species of SHP. Using the immunoscreening method, we identified and cloned a novel gene encoding a 19-kD protein, named TA-19, which proved to be specifically recognized in the bronchoalveolar lavage (BAL) fluids and sera of patients with SHP. IgG, IgA, and IgM antibodies to the recombinant TA-19 protein were significantly elevated in the sera as well as in the BAL fluids from SHP patients compared with those from non-SHP groups. This protein also induced SHP-specific proliferation of the mononuclear cells from both the peripheral blood and BAL. These results reveal that TA-19 derived from T. asahii may play a relevant role in specific cellular and humoral immune responses in patients with SHP.

Administration, Inhalation↗
PubMed2004

Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal colic.

BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's specialised register (May 2003), the Cochrane Central Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and measurements on continuous scales are reported as weighted mean differences (WMD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient-reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. REVIEWER'S CONCLUSIONS: Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine.

Analgesics, Opioid↗
PubMed1996

Immobilizing proteins on the surface of yeast cells.

Yeast has a rigid cell wall comprising an outer layer of glycoproteins and an internal skeletal layer of glucan; heterologous proteins can be targeted to the glycoprotein layer and become covalently linked to the glucan skeleton. Yeast is a eukaryote that has 'generally regarded as safe' (GRAS) status, and is easy to cultivate, so it seems ideally suited for applications including the manufacture of recyclable, immobilized, biocatalysts, whole-cell vaccines, the presentation of peptide or antibody libraries, and the presentation of adhesion or metal-binding proteins.

Administration, Oral↗
PubMedDate not supplied

Antibodies and genetically engineered related molecules: production and purification.

Antibodies and antibody derivatives constitute 20 % of biopharmaceutical products currently in development, and despite early failures of murine products, chimeric and humanized monoclonal antibodies are now viable therapeutics. A number of genetically engineered antibody constructions have emerged, including molecular hybrids or chimeras that can deliver a powerful toxin to a target such as a tumor cell. However, the general use in clinical practice of antibody therapeutics is dependent not only on the availability of products with required efficacy but also on the costs of therapy. As a rule, a significant percentage (50-80%) of the total manufacturing cost of a therapeutic antibody is incurred during downstream processing. The critical challenges posed by the production of novel antibody therapeutics include improving process economics and efficiency, to reduce costs, and fulfilling increasingly demanding quality criteria for Food and Drug Administration (FDA) approval. It is anticipated that novel affinity-based separations will emerge from the development of synthetic ligands tailored to specific biotechnological needs. These synthetic affinity ligands include peptides obtained by synthesis and screening of peptide combinatorial libraries and artificial non-peptidic ligands generated by a de novo process design and synthesis. The exceptional stability, improved selectivity, and low cost of these ligands can lead to more efficient, less expensive, and safer procedures for antibody purification at manufacturing scales. This review aims to highlight the current trends in the design and construction of genetically engineered antibodies and related molecules, the recombinant systems used for their production, and the development of novel affinity-based strategies for antibody recovery and purification.

Animals↗
PubMed1980

A survey of career assistance programs at U.S. dental schools.

1. There is a perceived need among the leaders of our dental schools for career assistance programs for dental students. 2. Current programs and services for transmitting career assistance at a majority of dental educational institutions are either nonexistent or sporadic, and handled informally without carefully coordinated activities. 3. The most frequently used career assistance services, where programs do exist, are a library of career informational materials, formalized arrangements with outside professionals in the community, and placement services. 4. Among the variety of individuals coordinating current programs in career assistance in dental schools, the most common is a member of the administration (primarily the director of student affairs).

Career Choice↗