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PubMed2002

Identification of potential protective antigens of Ostertagia ostertagi with local antibody probes.

The identification of protective helminth antigens remains the most important challenge in the development of parasitic vaccines. To identify protective antigens of Ostertagia ostertagi, an important abomasal parasite of cattle, parasite-specific local antibodies from the abomasal mucus and from the draining lymph nodes were collected from calves immunized with multiple infections and from 'primary infected' animals. With these probes, Western blots of extracts and excretion/ secretion (E/S) material from L3, L4 and adult life-stages as well as cDNA expression libraries were screened to identify antigens that were exclusively recognized by antibodies from 'immunized' calves. In the adult stage, a protein of 32 kDa was specifically detected on Western blot by mucus antibodies from 'immunized' animals. In the L3 and L4 larval stages, proteins situated in the regions of 28-29 kDa were recognized by mucus antibodies and a 59 kDa antigen was specifically recognized by lymph node antibodies from 'immunized' animals. Screening E/S material revealed no specific difference in recognition pattern between 'immunized' and 'primary infected' animals. Screening of the cDNA libraries revealed 26 relevant clones, coding for 15 proteins, among these several with potential protective capacity, immunodominant properties or functional and physiological importance e.g. metalloproteases, an aspartyl protease inhibitor and collagen.

Animals↗
PubMedDate not supplied

A hierarchical clustering approach for large compound libraries.

A modified version of the k-means clustering algorithm was developed that is able to analyze large compound libraries. A distance threshold determined by plotting the sum of radii of leaf clusters was used as a termination criterion for the clustering process. Hierarchical trees were constructed that can be used to obtain an overview of the data distribution and inherent cluster structure. The approach is also applicable to ligand-based virtual screening with the aim to generate preferred screening collections or focused compound libraries. Retrospective analysis of two activity classes was performed: inhibitors of caspase 1 [interleukin 1 (IL1) cleaving enzyme, ICE] and glucocorticoid receptor ligands. The MDL Drug Data Report (MDDR) and Collection of Bioactive Reference Analogues (COBRA) databases served as the compound pool, for which binary trees were produced. Molecules were encoded by all Molecular Operating Environment 2D descriptors and topological pharmacophore atom types. Individual clusters were assessed for their purity and enrichment of actives belonging to the two ligand classes. Significant enrichment was observed in individual branches of the cluster tree. After clustering a combined database of MDDR, COBRA, and the SPECS catalog, it was possible to retrieve MDDR ICE inhibitors with new scaffolds using COBRA ICE inhibitors as seeds. A Java implementation of the clustering method is available via the Internet (http://www.modlab.de).

Algorithms↗
PubMed1997

Practice libraries: managing printed information and meeting the information needs of staff in general practice.

Librarians and GPs share an interest in exploring different approaches to providing information to general practice and improving information management within it. Describing the aims, policy, collections, enquiries and services of three Practice Libraries in the Aylesbury area, this paper demonstrates that an information professional can make a significant impact on the management of printed information whilst facilitating access to external sources. A wealth of opportunities lie ahead for those willing to apply information handling skills to general practice. Medical librarians will need to strike a careful balance between providing direct access to sources and the development of information services tailored to meet the needs of primary health care workers.

Audiovisual Aids↗
PubMedDate not supplied

Direct-injection NMR (DI-NMR): a flow NMR technique for the analysis of combinatorial chemistry libraries.

A new tool for analyzing compound libraries by NMR has been developed. Aliquots of solution-state samples (between 120 and 350 microL) are directly injected, using a standard liquids handler, into an NMR (LC-NMR) flow probe. Automated NMR software tracks--and suppresses--intense signals arising from the nondeuterated solvents used (if any) and acquires high-sensitivity one-dimensional 1H NMR spectra. An 88-member combinatorial library, dissolved in DMSO and stored in a 96-well microtiter plate, has been analyzed a number of ways using this technique. This nondestructive technique, which we call direct-injection NMR (DI-NMR) and which is embodied in our versatile automated sample changer (VAST) hardware, has proven to be both routine and robust. Our success in automatically acquiring the NMR data for entire plates of library compounds (within 4-8 h) has caused us to develop new ways to display and analyze the resulting NMR data, as will be shown here.

Chemistry, Organic↗
PubMed1992

Cloning of an ovine 11 beta-hydroxysteroid dehydrogenase complementary deoxyribonucleic acid: tissue and temporal distribution of its messenger ribonucleic acid during fetal and neonatal development.

Glucocorticoids promote the development of many organ systems vital for extrauterine survival, and fetal cortisol provides the trigger for birth in sheep. The activity of glucocorticoids may be influenced at a cellular level by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which is responsible for the interconversion of cortisol and cortisone. To examine 11 beta-HSD gene expression during fetal development, two overlapping clones which yield a 1.4 kilobase (kb) complementary DNA encoding sheep 11 beta-HSD from a liver library were isolated by using a rat 11 beta-HSD cDNA as the probe. This cDNA contains a 879 base pair open reading frame for a protein of 292 amino acids that has more than 70% sequence identity to rat and human 11 beta-HSDs. To define the tissue distribution of 11 beta-HSD messenger RNA in sheep, selected tissues were collected from one fetus at day 130 and term (approximately 145 days), and from a nonpregnant ewe. Cellular RNA was extracted and subjected to Northern blot analysis, and a single 1.8 kb transcript was detected in the fetal and adult liver, lung, hypothalamus, anterior pituitary, and placenta. This was undetectable in adrenals and kidneys, but a smaller (1.5 kb) transcript was present in fetal and adult kidney RNA. The relative abundance of 11 beta-HSD mRNA was greatest in fetal and adult livers, and it was much higher in adult liver, lung, and kidney than in the corresponding fetal tissues. To examine whether 11 beta-HSD gene expression is developmentally regulated in the fetal sheep, liver, lung, and kidney tissues were taken from fetuses at day 60-70, day 100-110, day 125-130, at term, and from newborn lambs (24-48 h old). In the lung and kidney, the relative abundance of 11 beta-HSD mRNA did not change from day 60 to term but increased in the lungs of newborn lambs. In contrast, 11 beta-HSD mRNA levels in the liver increased between day 125 and term and rose further in the newborn. Collectively, these results demonstrate that 11 beta-HSD gene expression in sheep is regulated in a tissue-specific and developmentally programmed manner.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

The computer-literate nurse.

This study investigated the perceptions of nursing educators concerning the amount and kinds of computer training that should occur in the nursing degree program. Data were collected in two phases: a semi-structured interview of experts in the application of the computer to nursing and a random sample of nursing educators in 2-year and 4-year nursing degree programs. The panel of experts identified objectives within each of seven domains: programming and algorithms, skills in computer usage, major uses and applications, limitations of computers, personal and social aspects, and relevant values and attitudes. The responses of this panel were used to generate an universe of computer literacy objectives. The sample of nursing educators then identified a subset of objectives within the universe that they felt nursing students should master in order to be computer literate. The survey found that nursing educators desire graduates of nursing degree programs to understand how a computer works and to develop skills in using application programs. They do not expect nursing graduates to acquire programming skills, however, they do expect the graduates to acquire skills in using the computer as a tool in nursing. These skills include using a word processor for writing nursing care plans, using computer-aided instruction as a learning tool, using a hospital computer information system, using a computerized library database, and using software for statistical computations.

Computer Literacy↗
PubMed1999

Library residencies and internships as indicators of success: evidence from three programs.

This paper discusses post-master's degree internships in three very different organizations; the University of Illinois at Chicago, the National Library of Medicine, and the Library of Congress. It discusses the internships using several questions. Do the programs serve as a recruitment strategy? Do the programs develop key competencies needed by the participant or organization? Do the programs develop leaders and managers? Is acceptance into a program an indicator of future career success? A survey was mailed to 520 persons who had completed internships in one of the three programs. There was a 49.8% response rate. Responses to fifty-four questions were tabulated and analyzed for each program and for the total group. The results confirm the value of internships to the career of participants.

Adult↗
PubMed2001

EsMlp, a muscle-LIM protein gene, is up-regulated during cold exposure in the freeze-avoiding larvae of Epiblema scudderiana.

Screening of a cDNA library identified transcripts that were up-regulated by cold (4 or -20 degrees C) exposure in larvae of the freeze-avoiding goldenrod gall moth, Epiblema scudderiana. One clone contained a full-length open reading frame encoding a protein of 94 amino acids. The gene product, with 79.1% of residues identical with the Drosophila LIM protein Mlp60A, was named EsMlp and contained a single LIM domain and consensus sequences characteristic of a LIM protein. Transcript levels rose approx twofold when larvae were shifted from 4 to -20 degrees C and approx threefold over the midwinter months compared with larvae sampled in October or April. EsMlp expression was high in larval head (possibly due to expression in pharyngeal muscles) and body wall but was not detected in fat body. Immunoblotting revealed a three- to fourfold increase in EsMlp protein in midwinter larvae (January-February) compared with November-collected animals and a further rise to eightfold higher than November values in larvae collected in April. Cold up-regulation of EsMlp and the pattern of EsMlp levels in the larvae suggest possible roles for the protein, such as in muscle maintenance over the winter or as a preparative function that could facilitate the rapid resumption of development and metamorphosis when environmental temperatures rise in the spring.

Amino Acid Sequence↗
PubMed2003

Screening children in the first four years of life to undergo early treatment for otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) is the most common cause of acquired hearing loss in childhood and has been associated with delayed language development and behavioural problems. This condition has a prevalence of about 20% at the age of two years, a time of rapid language development. It is most often asymptomatic. Effective treatment exists for clearing effusions. Some have argued, therefore, that children should be screened and treated early if found to have clinically important OME. However, there is a high rate of spontaneous resolution of effusions and for some children, effusions may represent a physiological response that does not reduce hearing significantly or impact negatively on language development or behaviour. Previous reviews of the effect of screening and treatment have included studies using non-randomised designs. OBJECTIVES: The aim of this review was to assess evidence from randomised controlled trials about the effectiveness, on language and behavioural outcomes, of screening and treating children with clinically important OME in the first four years of their life. The focus was on the first four years of life because this is the time of most rapid language development. The consequences of hearing loss are likely to be most serious during this time. In addition, children of this age are least likely to be able to report or seek help for impaired hearing, particularly if these problems have a slow onset and are subtle. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (the Cochrane Library Issue 1, 2002), MEDLINE (1966-2002) and EMBASE (1974-2002) (all in February 2002) and reference lists of all studies. We also contacted the first authors of the studies we included in this review. SELECTION CRITERIA: 1. Randomised controlled trials evaluating interventions for OME among children with OME identified through screening. 2. Comparison of outcomes for children randomised to be screened for OME and outcomes for children who were not randomised to be screened for OME. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: We identified no trials comparing outcomes for children randomised to be screened for OME with outcomes for children who were not randomised to be screened for OME. We identified three trials evaluating interventions for OME among children with OME identified through screening. From these trials, we found no evidence of clinically important benefit in language development from screening and treating children with clinically important OME. Although there was a beneficial effect on the resolution of OME and improved hearing in the short-term (six months), this effect largely disappeared in the long-term (12 months). REVIEWER'S CONCLUSIONS: The identified randomised trials do not show an important benefit from screening of the general population of asymptomatic children in the first four years of life for OME on language development and behaviour.

Child, Preschool↗
PubMed2004

Comprehensive EST analysis of tomato and comparative genomics of fruit ripening.

A large tomato expressed sequence tag (EST) dataset (152 635 total) was analyzed to gain insights into differential gene expression among diverse plant tissues representing a range of developmental programs and biological responses. These ESTs were clustered and assembled to a total of 31 012 unique gene sequences. To better understand tomato gene expression at a plant system level and to identify differentially expressed and tissue-specific genes, we developed and implemented a digital expression analysis protocol. By clustering genes according to their relative abundance in the various EST libraries, expression patterns of genes across various tissues were generated and genes with similar patterns were grouped. In addition, tissues themselves were clustered for relatedness based on relative gene expression as a means of validating the integrity of the EST data as representative of relative gene expression. Arabidopsis and grape EST collections were also characterized to facilitate cross-species comparisons where possible. Tomato fruit digital expression data was specifically compared with publicly available grape EST data to gain insight into molecular manifestation of ripening processes across diverse taxa and resulted in identification of common transcription factors not previously associated with ripening.

Arabidopsis↗
PubMed2006

Physical map of the wheat high-grain protein content gene Gpc-B1 and development of a high-throughput molecular marker.

Grain protein content (GPC) is important for human nutrition and has a strong influence on pasta and bread quality. A quantitative trait locus, derived from a Triticum turgidum ssp. dicoccoides accession (DIC), with an average increase in GPC of 14 g kg(-1) was mapped on chromosome 6BS. Using the wheat-rice colinearity, a high-density map of the wheat region was developed and the quantitative trait locus was mapped as a simple Mendelian locus designated Gpc-B1. A physical map of approx. 250 kb of the Gpc-B1 region was developed using a tetraploid wheat bacterial artificial chromosome library. The constructed physical map included the two Gpc-B1 flanking markers and one potential candidate gene from the colinear rice region completely linked to Gpc-B1. The relationship between physical and genetic distances and the feasibility of isolating genes by positional cloning in wheat are discussed. A high-throughput codominant marker, Xuhw89, was developed. A 4-bp deletion present in the DIC allele was absent in a collection of 117 cultivated tetraploid and hexaploid wheat germplasm, suggesting that this marker will be useful to incorporate the high GPC allele from the DIC accession studied here into commercial wheat varieties.

Chromosomes, Plant↗
PubMed2026

Predictive Models for Hypoglycemia Risk in Haemodialysis Patients With Diabetic Kidney Disease: Systematic Review and Meta-Analysis.

AIM: To provide evidence for selecting and developing reliable clinical assessment tools for hypoglycemia in diabetic kidney disease patients during haemodialysis. DESIGN: Review. METHODS: Systematic searches were performed in 9 Chinese and English databases to collect literature regarding the development of hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease. Two reviewers independently performed literature screening, data extraction, risk-of-bias assessment, and applicability evaluation. The Prediction Model Risk of Bias Assessment Tool was used to assess the risk of bias and applicability of the included studies. Meta-analysis was conducted using R software. DATA SOURCES: CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase, Web of Science, and CINAHL. The search period covered from the establishment date of each database to December 2025. RESULTS: Six studies, comprising six prediction models, were included. Two studies performed internal validation, and three conducted external validation. All models reported the area under the curve, ranging from 0.813 to 0.866, and calibration measures. Four studies were rated as having a high risk of bias, while all six demonstrated good overall applicability. The meta-analysis showed that the pooled AUC value of the six studies was 0.846 (95% CI: 0.823-0.867). CONCLUSION: Research on hypoglycemia risk prediction models in haemodialysis patients with diabetic kidney disease remains in the developmental stage. Although the included prediction models exhibited satisfactory apparent discriminatory ability and clinical applicability, most of the original studies suffered from a high risk of bias and lacked adequate validation. The true predictive performance and clinical application value of these models remain to be further verified. Accordingly, routine and unconditional clinical application is not recommended at this stage. Future studies should include more high-quality, multicenter external validation and develop models with high generalizability, favourable clinical applicability, and robust predictive performance to facilitate early identification of hypoglycemia risk in this population. IMPACT: This study systematically evaluated the hypoglycemia risk prediction models for diabetic kidney disease patients during haemodialysis, and the research on hypoglycemia risk prediction models for maintenance haemodialysis patients during dialysis is still in the development stage. This study provides a reference for clinical medical staff to select or develop hypoglycemia risk prediction and assessment tools for diabetic kidney disease patients during haemodialysis. REPORTING METHOD: This study was conducted in accordance with the relevant guidelines of the EQUATOR Network and followed the TRIPOD-SRMA Checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. TRIAL REGISTRATION: PROSPERO: CRD420251243352.

Humans↗
PubMed2003

Prospective study of the performance of vibrational spectroscopies for rapid identification of bacterial and fungal pathogens recovered from blood cultures.

Rapid identification of microbial pathogens reduces infection-related morbidity and mortality of hospitalized patients. Raman spectra and Fourier transform infrared (IR) spectra constitute highly specific spectroscopic fingerprints of microorganisms by which they can be identified. Little biomass is required, so that spectra of microcolonies can be obtained. A prospective clinical study was carried out in which the causative pathogens of bloodstream infections in hospitalized patients were identified. Reference libraries of Raman and IR spectra of bacterial and yeast pathogens highly prevalent in bloodstream infections were created. They were used to develop identification models based on linear discriminant analysis and artificial neural networks. These models were tested by carrying out vibrational spectroscopic identification in parallel with routine diagnostic phenotypic identification. Whereas routine identification has a typical turnaround time of 1 to 2 days, Raman and IR spectra of microcolonies were collected 6 to 8 h after microbial growth was detected by an automated blood culture system. One hundred fifteen samples were analyzed by Raman spectroscopy, of which 109 contained bacteria and 6 contained yeasts. One hundred twenty-one samples were analyzed by IR spectroscopy. Of these, 114 yielded bacteria and 7 were positive for yeasts. High identification accuracy was achieved in both the Raman (92.2%, 106 of 115) and IR (98.3%, 119 of 121) studies. Vibrational spectroscopic techniques enable simple, rapid, and accurate microbial identification. These advantages can be easily transferred to other applications in diagnostic microbiology, e.g., to accelerate identification of fastidious microorganisms.

Bacteria↗
PubMed2001

[Corpus Hermeticum in history].

The originator and founder of hermetism was the mythical Hermes Trismegistos, a deity of the syncretic Hellenistic religion that came into being through the identification of the Greek god Hermes with the Egyptian god Thot. In later Hellenistsic times various hermetic writers considered Hermes Trismegistos to have been a historical personage, a king, prophet and philosopher (physician), as well as author of many widely disseminated writings that made up the so-called Corpus Hermeticum (eighteen separate treatises from the 2nd-4th centuries AD) and the so-called Emerald Table (Tabula Smaragdina). The Corpus Hermeticum is a collection of treatises of a philosophical, religious, theological as well as theosophical nature. The collection played an important role in the development of the philosophy of alchemy and hermetism, and formed the basis for an alchemist philosophy of nature. There are currently two views among scholars on the origins of hermetism. According to one, hermetism derived directly from Egypt, while according to the other it orginated in Greece. In the years 1945-46 a number of hermetic texts forming part of the now famous gnostic "library" were discovered in Nag-Hammadi (Chenosboskion) in Upper Egypt. The Coptic texts from Nag-Hammadi date from the middle of the 4th century AD, and according to experts are translations from the Greek. Some authors (R. Reitzenstein and T. Zieliński) have suggested that along with the appearance in Egypt of the Hermetic Books, attributed to Hermes Trismegistos, there also appeared a new god in Egypt, Poimandres, and a new religion was established, hermetism, which competed for influence with Christianity. The present article discusses the main of the hermetic treatises, including Poimandres, which contains an account of the creation of the world. The article also discusses the reasons for the decline of hermetism as a religion and stresses that in spite of this decline the doctrine managed to survive in the form of alchemic hermetism, which played an important role in the culture of the Renaissance. The article also cites the voluminous work by W. Scott and A. S. Ferguson (1924-1936), and A. D. Nock and A. -J. Festugiére (1945-1964), which contains contemporary, English and French, commentaries on and translations of the Corpus Hermeticum texts.

Alchemy↗
PubMed2004

Gene expression profile of the rat eye iridocorneal angle: NEIBank expressed sequence tag analysis.

PURPOSE: To characterize gene expression pattern in the combined tissues of the rat iridocorneal angle by expressed sequence tag (EST) analysis, as part of the NEIBank project. METHODS: RNA was extracted from dissected tissues of the rat iridocorneal angle (iris, ciliary body, trabecular meshwork, and Schlemm's canal) and used to construct unamplified, non-normalized cDNA libraries in the pSPORT1 vector. Approximately 5000 clones were sequenced from the 5'-end. Clones were clustered and identified using the GRIST software, a procedure based on BLAST comparisons. Complete sequences of several novel cDNAs showing eye-preferred expression patterns were obtained. The expression patterns of several genes have been investigated by Northern blot and in situ hybridization, as well as by RT-PCR. RESULTS: After analysis and removal of non-mRNA sequences, 2195 independent clusters, potentially representing individual eye angle-expressed clones were obtained. The expression profile of the combined rat eye angle tissues was more similar to that of the human iris than to human trabecular meshwork. Several cDNAs encoding transcription factors essential for normal eye development and function including Pax-6, Six3, c-Maf, Maf1, Sox-4, Foxc1, Rx, and Ldb2 were present among sequenced clones. A number of tested cDNAs showed eye-preferred expression patterns. Myocilin, which is abundant in human eye angle tissues, was not observed in the rat collection; however, transcripts for three other olfactomedin-domain proteins were seen. Latrotoxin receptor (CL1AA) and optimedin were shown to be expressed in the iris and ciliary body, as well as in the ganglion and inner nuclear cell layers of the retina, whereas the rat orthologue of the human HNOEL-iso gene was expressed in the iris and sclera and less actively in the trabecular meshwork, retina, and optic nerve. CONCLUSIONS: The iridocorneal libraries are a good source of novel uncharacterized genes and molecular markers for the tissues of the eye angle. Although myocilin is not abundantly expressed in rat eye angle, other olfactomedin-containing genes are expressed there and may play important roles in normal eye function and disease.

Amino Acid Sequence↗
PubMed1984

Integrating library services and continuing education.

This paper presents an innovative integration of library services and continuing education (CE). While print material is an important continuing education information source for physicians, its volume is overwhelming. Librarians have developed the use of a variety of methods, including online data bases such as MEDLINE, to simplify and expedite access to printed information. Combining a library information delivery system with formal continuing education course activities can enhance the educational potential of two popular learning methods.

Data Collection↗
PubMed2004

Thyrotropin-releasing hormone added to corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease.

BACKGROUND: Thyrotropin-releasing hormones (TRH) added to prenatal corticosteroids has been suggested as a way to further reduce breathing problems and neonatal lung disease in infants born preterm. OBJECTIVES: To assess the effect of giving prenatal TRH in addition to corticosteroids to women at risk of very preterm birth for the prevention of neonatal respiratory disease. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1965 to July 2003), EMBASE (1988 to July 2003), Current Contents (1997 to July 2003). SELECTION CRITERIA: Randomised controlled trials in women at sufficient risk of preterm birth to warrant the use of prenatal corticosteroids to promote lung maturity. TRH and corticosteroids were compared with corticosteroids with or without placebo. The main outcomes considered were fetal and infant mortality, infant morbidity, childhood development and maternal morbidity. DATA COLLECTION AND ANALYSIS: All assessments of trial eligibility, quality and data extractions were done by at least two authors independently. MAIN RESULTS: Over 4600 women were recruited into the 13 included trials. Five trials were rated of high quality. Overall, prenatal TRH, in addition to corticosteroids, did not reduce the risk of neonatal respiratory disease or chronic oxygen dependence, and did not improve any of the fetal, neonatal or childhood outcomes assessed by intention to treat analyses.Indeed, the data showed prenatal TRH to have adverse effects for women and their infants. All side-effects monitored were more likely to occur in women receiving TRH. In the infants, prenatal TRH increased the risk of needing ventilation (relative risk (RR) 1.16, 95% confidence interval (CI) 1.03 to 1.29, 3 trials, 1969 infants), having a low Apgar score at five minutes (RR 1.48, 95% CI 1.14 to 1.92, 3 trials, 1969 infants) and, for the two trials providing data, was associated with poorer outcomes at childhood follow up. Sensitivity analyses by trial quality, or subgroups with differing times from entry to birth, or different dose regimens of TRH, did not change these findings. REVIEWERS' CONCLUSIONS: Prenatal thyrotropin-releasing hormones, in addition to corticosteroids, given to women at risk of very preterm birth do not improve infant outcomes and can cause maternal side-effects.

Drug Therapy, Combination↗
PubMed2005

Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model.

Neuronal cell death in HD is believed to be largely a dominant cell-autonomous effect of the mutant huntingtin protein. We previously developed an inducible PC12 cell model which expresses an N-terminal huntingtin fragment with an expanded poly Q repeat (N63-148Q) under the control of the tet-off system. In order to evaluate the ability of compounds to protect against mutant huntingtin toxicity in our model, we measured LDH released by dead cells into the medium. We have now screened the library of 1040 compounds from the NINDS Custom Collection as part of a National Institute of Neurological Disorders and Stroke (NINDS) collaborative project. Each positive compound was tested at 3-8 concentrations. Five compounds significantly attenuated mutant huntingtin (htt)-induced LDH release without affecting the expression level of huntingtin and independent of effect on aggregates. We also tested a broad spectrum caspase inhibitor Z-VAD-fmk and previously proposed candidate compounds. This cell model can provide a method to screen potential therapeutic compounds for treating Huntington's disease.

Amino Acid Chloromethyl Ketones↗