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PubMedDate not supplied

MEDLINE, cancer-CD, SCI-CD addition on CD-ROM.

Compact Disc Read-Only-Memory, CD-ROM, is a powerful resource which combines the best features of both online and print access to the literature: multiple access points and leisurely browsing (online accessibility without a modem or without its cost). Applied to the MEDLINE database, this technology has created a brand new market, one which is increasingly competitive and therefore evolving rapidly. Five MEDLINE and two non-MEDLINE products are reviewed. The MEDLINE products include: BRS/COLLEAGUE DISC, Compact Cambridge, Ebsco's Core MEDLINE, Online Research System's Compact Med-Base, and SilverPlatter's MEDLINE on CD-ROM. The two other products include: Institute for Scientific Information's SCI CD Edition and SilverPlatter's CANCER-CD. The market is still wide open and the buyer is wise to try before he buys. However, there are great differences between the various packagings of a rather familiar product. In our view, in terms of ease of use, SilverPlatter was the clear winner. Ebsco's product is attractive because of its containment on one CD. Med-Base is the most original and offers special features not found elsewhere. Finally, personal preference is a strong consideration and should not be overlooked.

MEDLARS↗
PubMed2005

Letter from the editor: Adenosine-to-inosine RNA editing in Alu repeats in the human genome.

Adenosine-to-inosine (A-to-I) RNA editing increases the complexity of the human transcriptome and is essential for maintenance of normal life in mammals. Most A-to-I substitutions occur within repetitive elements in the genome, mainly in Alu repeats. The phenomenon of A-to-I editing is far less abundant in mice, rats, chickens and flies than in humans, which correlates with the relative under-representation of Alu repeats in these non-primate genomes. Here, we review the recent results of bioinformatic and laboratory approaches that have estimated the extent of the editing phenomenon. We discuss the possible biological relevance of the editing pathway, its possible interaction with other cellular pathways that respond to double-stranded RNA and its possible contribution to the accelerated evolution of primates.

Adenosine↗
PubMed2005

An aminoacyl-tRNA synthetase with a defunct editing site.

Many aminoacyl-tRNA synthetases (aaRSs) contain two active sites, a synthetic site catalyzing aminoacyl-adenylate formation and tRNA aminoacylation and a second editing or proofreading site that hydrolyzes misactivated adenylates or mischarged tRNAs. The combined activities of these two sites lead to rigorous accuracy in tRNA aminoacylation, and both activities are essential to LeuRS and other aaRSs. Here, we describe studies of the human mitochondrial (hs mt) LeuRS indicating that the two active sites of this enzyme have undergone functional changes that impact how accurate aminoacylation is achieved. The sequence of the hs mt LeuRS closely resembles a bacterial LeuRS overall but displays significant variability in regions of the editing site. Studies comparing Escherichia coli and hs mt LeuRS reveal that the proofreading activity of the mt enzyme is disrupted by these sequence changes, as significant levels of Ile-tRNA(Leu) are formed in the presence of high concentrations of the noncognate amino acid. Experiments monitoring deacylation of Ile-tRNA(Leu) and misactivated adenylate turnover revealed that the editing active site is not operational. However, hs mt LeuRS has weaker binding affinities for both cognate and noncognate amino acids relative to the E. coli enzyme and an elevated discrimination ratio. Therefore, the enzyme achieves fidelity using a more specific synthetic active site that is not prone to errors under physiological conditions. This enhanced specificity must compensate for the presence of a defunct editing site and ensures translational accuracy.

Acylation↗
PubMed1993

Determinants of Ca2+ permeability in both TM1 and TM2 of high affinity kainate receptor channels: diversity by RNA editing.

GluR6, a subunit of high affinity kainate receptor channels in the mammalian CNS, carries a glutamine (Q) or arginine (R) residue in a critical position (Q/R site) of the putative channel-forming segment TM2. One form, GluR6(Q), is encoded by the GluR6 gene; the other, GluR6(R), is generated by RNA editing. Further analysis of cloned GluR6 cDNA revealed that two additional positions, located in transmembrane segment TM1, are diversified by RNA editing to generate either isoleucine (I) or valine (V) in one and tyrosine (Y) or cysteine (C) in the other TM1 position. In GluR6 channels, in contrast with AMPA receptor channels, the presence of Q in the TM2 Q/R site determines channels with low Ca2+ permeability, whereas an R determines a higher Ca2+ permeability if TM1 is fully edited. In the TM1 unedited form of GluR6, Ca2+ permeability is less dependent on the presence of either Q or R in TM2. Thus Ca2+ permeability of kainate receptor channels can vary, depending on editing of both TM1 and TM2.

Amino Acid Sequence↗
PubMed2006

Identification of a sequence motif critical for editing of a tobacco chloroplast transcript.

Nucleotides are specifically and efficiently targeted for modification from C to U within transcripts of chloroplasts in higher plants. Although the enzymatic apparatus responsible for altering C to U has not been identified, the sequences surrounding editing sites are known to contain information essential for efficient editing. We set out to determine the nucleotides that are critical for editing of a particular C, NTpsbE C214, in chloroplast transcripts in tobacco. Assay of editing of substrates with different lengths of 5' and 3' sequence around the target C was carried out to delimit the region of sequence critical for editing in vitro. Mutated substrates were then constructed with an altered nucleotide at each position within the previously defined region around NTpsbE C214. In individual nucleotides, both 5' and 3' of the edited nucleotide were found to be important for editing. The sequence GCCGUU, which occurs 5' of the editing site, was discovered to be critical for editing. Editing substrates mutated to alter the distance between the GCCGUU sequence and NTpsbE C214 resulted in the generation of a new editing target, the 3' adjacent nucleotide. These data are consistent with a model in which the selection of the C target for editing is determined by its distance from a crucial 5' sequence.

Arabidopsis Proteins↗
PubMed2003

RBP16 is a multifunctional gene regulatory protein involved in editing and stabilization of specific mitochondrial mRNAs in Trypanosoma brucei.

RBP16 is a Trypanosoma brucei mitochondrial RNA-binding protein that associates with guide RNAs (gRNAs), mRNAs, and ribosomal RNAs. Based on its inclusion in the multifunctional Y-box protein family and its ability to bind multiple RNA classes, we hypothesized that RBP16 plays a role in diverse aspects of mitochondrial gene regulation. To gain insight into RBP16 function, we generated cells expressing less than 10% of wild-type RBP16 levels by tetracycline-regulated RNA interference (RNAi). Poisoned primer extension analyses revealed that edited, but not unedited, CYb mRNA is reduced by approximately 98% in tetracycline-induced RBP16 RNAi cells, suggesting that RBP16 is critical for CYb RNA editing. The down-regulation of CYb editing in RBP16 RNAi transfectants apparently entails a defect in gRNA utilization, as gCYb[560] abundance is similar in uninduced and induced cells. We observed a surprising degree of specificity regarding the ability of RBP16 to modulate editing, as editing of mRNAs other than CYb is not significantly affected upon RBP16 disruption. However, the abundance of the never edited mitochondrial RNAs COI and ND4 is reduced by 70%-80% in RBP16 RNAi transfectants, indicating an additional role for RBP16 in the stabilization of these mRNAs. Analysis of RNAs bound to RBP16 immunoprecipitated from wild-type cells reveals that RBP16 is associated with multiple gRNA sequence classes in vivo, including those whose abundance and usage appear unaffected by RBP16 disruption. Overall, our results indicate that RBP16 is an accessory factor that regulates the editing and stability of specific populations of mitochondrial mRNAs.

Animals↗
PubMed2000

Trypanosoma brucei guide RNA poly(U) tail formation is stabilized by cognate mRNA.

Guide RNAs (gRNAs) are small RNAs that provide specificity for uridine addition and deletion during mRNA editing in trypanosomes. Terminal uridylyl transferase (TUTase) adds uridines to pre-mRNAs during RNA editing and adds a poly(U) tail to the 3' end of gRNAs. The poly(U) tail may stabilize the association of gRNAs with cognate mRNA during editing. Both TUTase and gRNAs associate with two ribonucleoprotein complexes, I (19S) and II (35S to 40S). Complex II is believed to be the fully assembled active editing complex, since it contains pre-edited mRNA and enzymes thought necessary for editing. Purification of TUTase from mitochondrial extracts resulted in the identification of two chromatographically distinct TUTase activities. Stable single-uridine addition to different substrate RNAs is performed by the 19S complex, despite the presence of a uridine-specific 3' exonuclease within this complex. Multiple uridines are added to substrate RNAs by a 10S particle that may be an unstable subunit of complex I lacking the uridine-specific 3' exonuclease. Multiple uridines could be stably added onto gRNAs by complex I when the cognate mRNA is present. We propose a model in which the purine-rich region of the cognate mRNA protects the uridine tail from a uridine exonuclease activity that is present within the complex. To test this model, we have mutated the purine-rich region of the pre-mRNA to abolish base-pairing interaction with the poly(U) tail of the gRNA. This RNA fails to protect the uridine tail of the gRNA from exoribonucleolytic trimming and is consistent with a role for the purine-rich region of the mRNA in gRNA maturation.

Animals↗
PubMed2006

Reconstitution of full-round uridine-deletion RNA editing with three recombinant proteins.

Uridine (U)-insertion/deletion RNA editing in trypanosome mitochondria involves an initial cleavage of the preedited mRNA at specific sites determined by the annealing of partially complementary guide RNAs. An involvement of two RNase III-containing core editing complex (L-complex) proteins, MP90 (KREPB1) and MP61 (KREPB3) in, respectively, U-deletion and U-insertion editing, has been suggested, but these putative enzymes have not been characterized or expressed in active form. Recombinant MP90 proteins from Trypanosoma brucei and Leishmania major were expressed in insect cells and cytosol of Leishmania tarentolae, respectively. These proteins were active in specifically cleaving a model U-deletion site and not a U-insertion site. Deletion or mutation of the RNase III motif abolished this activity. Full-round guide RNA (gRNA)-mediated in vitro U-deletion editing was reconstituted by a mixture of recombinant MP90 and recombinant RNA editing exonuclease I from L. major, and recombinant RNA editing RNA ligase 1 from L. tarentolae. MP90 is designated REN1, for RNA-editing nuclease 1.

Amino Acid Sequence↗
PubMed1999

Polyadenylation occurs at multiple sites in maize mitochondrial cox2 mRNA and is independent of editing status.

Polyadenylation of nucleus-encoded transcripts has a well-defined role in gene expression. The extent and function of polyadenylation in organelles and prokaryotic systems, however, are less well documented. Recent reports of polyadenylation-mediated RNA destabilization in Escherichia coli and in vascular plant chloroplasts prompted us to look for polyadenylation in plant mitochondria. Here, we report the use of reverse transcription-polymerase chain reaction to map multiple polyadenylate addition sites in maize mitochondrial cox2 transcripts. The lack of sequence conservation surrounding these sites suggests that polyadenylation may occur at many 3' termini created by endoribonucleolytic and/or exoribonucleolytic activities, including those activities involved in 3' end maturation. Endogenous transcripts could be efficiently polyadenylated in vitro by using maize mitochondrial lysates with an activity that added AMP more efficiently than GMP. Polyadenylated substrates were tested for stability in maize mitochondrial S100 extracts, and we found that, compared with nonpolyadenylated RNAs, the polyadenylated substrates were less stable. Taken together with the low abundance of polyadenylated RNAs in maize mitochondria, our results are consistent with a degradation-related process. The fact that polyadenylation does not dramatically destabilize plant mitochondrial transcripts, at least in vitro, is in agreement with results obtained for animal mitochondria but differs from those obtained for chloroplasts and E. coli. Because fully edited, partially edited, and unedited transcripts were found among the cloned polyadenylated cox2 cDNAs, we conclude that RNA editing and polyadenylation are independent processes in maize mitochondria.

Adenosine Monophosphate↗
PubMed2005

Minimal pre-mRNA substrates with natural and converted sites for full-round U insertion and U deletion RNA editing in trypanosomes.

Trypanosome RNA editing by uridylate insertion or deletion cycles is a mitochondrial mRNA maturation process catalyzed by multisubunit complexes. A full-round of editing entails three consecutive steps directed by partially complementary guide RNAs: pre-mRNA cleavage, U addition or removal, and ligation. The structural and functional composition of editing complexes is intensively studied, but their molecular interactions in and around editing sites are not completely understood. In this study, we performed a systematic analysis of distal RNA requirements for full-round insertion and deletion by purified editosomes. We define minimal substrates for efficient editing of A6 and CYb model transcripts, and established a new substrate, RPS12. Important differences were observed in the composition of substrates for insertion and deletion. Furthermore, we also showed for the first time that natural sites can be artificially converted in both directions: from deletion to insertion or from insertion to deletion. Our site conversions enabled a direct comparison of the two editing kinds at common sites during substrate minimization and demonstrate that all basic determinants directing the editosome to carry out full-round insertion or deletion reside within each editing site. Surprisingly, we were able to engineer a deletion site into CYb, which exclusively undergoes insertion in nature.

Adenosine Triphosphatases↗
PubMed2004

Detection of alcohol use disorders in general hospital admissions in the United States.

BACKGROUND: Previous studies in which research-based assessment for alcohol problems at admission was compared with physician diagnoses indicated that many alcohol diagnoses in hospitalized patients were missed. We estimated the extent to which hospital records documented detection of alcohol abuse or dependence and other alcohol-related problems in a national sample of hospital admissions having a research-based diagnosis of alcohol use disorder ("interview-positive admissions"). We also estimated rates of inpatient alcohol intervention and referral for treatment. METHODS: A complex, multistage, probability sample was designed to represent nonmaternity, acute-care admissions to nonfederal, short-stay, general hospitals in the contiguous United States. The study included 2040 admissions, 1613 male and 427 female. Research-based diagnoses of current (ie, past 12 months) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol use disorder were derived from a structured, computer-assisted, personal interview containing the Alcohol Use Disorders and Associated Disabilities Interview Schedule. Information on detection, inpatient intervention, and treatment referral were obtained via retrospective analysis of closed hospital records covering the index visit. RESULTS: Record-documented diagnoses of alcohol-related problems were found in 40% to 42% of interview-positive admissions. Inpatient intervention rate was estimated at 21% for interview-positive admissions, and treatment referral rate, 24%. For detected interview-positive admissions, estimated rates of intervention and referral were 50% and 53%, respectively. CONCLUSIONS: Estimated rates of detection, inpatient intervention, and treatment referral of alcohol use disorders in hospital admissions were low. Current-drinking hospital admissions should be screened for alcohol problems as part of the admission routine, with further professional evaluation, intervention, and treatment referral as indicated.

Adolescent↗
PubMed1998

[Classification and grading of gliomas and meningiomas].

GLIOMAS: As we demonstrated for supratentorial, diffuse gliomas in adults, a stratification into just two grades of malignancy, 'low' and 'high grade,' proved reliable and prognostically relevant. The discriminating histomorphological criterion for high-grade astrocytoma (WHO glioblastoma) as well as anaplastic oligodendroglioma and anaplastic oligoastrocytoma is endothelial hyperplasia/proliferation, which is usually associated with uptake of contrast medium in computed tomography and magnetic resonance imaging. As neoangiogenesis indicates glioma progression, it is worthwhile considering these radiographic features to judge the representativeness of the tumor samples critically. MENINGIOMAS: The revised edition of the WHO classification of brain tumors now includes the 'atypical' meningioma (WHO 'grade' II): Based on both its histomorphological features and prognosis, it should be placed between the common type and anaplastic meningioma. Nuclear area related Ki-67 proliferation indices, as determined by morphometry, were the prerequisite for outlining its histomorphological spectrum better. Cytogenetically, the most consistent progression-associated feature was loss of the distal part of the short arm of one chromosome 1 (1p-). Thus, a screening method using the tissue non-specific form of alkaline phosphatase (ALPL) as the respective marker enzyme was established. Diagnosing a meningioma of the intermediate type implies careful clinical and radiological patient follow-ups to detect tumor recurrences early.

Adult↗
PubMed1996

Measuring outcomes in psychiatry: an inpatient model.

BACKGROUND: This article describes a system for measuring outcomes recently implemented in the department of psychiatry of Baptist Memorial Hospital, a 78-bed inpatient and day treatment unit that represents one service line of a large, urban teaching hospital in Memphis. In June 1993 Baptist Hospital began a 15-month pilot test of PsychSentinel, a measurement tool developed by researchers in the Department of Community Medicine at the University of Connecticut. The hospital identified the following four primary goals for this pilot project: provide data for internal hospital program evaluation, provide data for external marketing in a managed care environment, satisfy requirements of the Joint Commission on Accreditation of Health Care Organizations, and generate studies that add to the literature in psychiatry and psychology. DESCRIPTION OF MEASURE: PsychSentinel is based on the standardized diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The outcome measure assesses the change in the number of symptoms of psychopathology that occurs between admission and discharge from the hospital. Included in the nonproprietary system are risk adjustment factors, as well as access to a national reference database for comparative analysis purposes. Data collection can be done by trained ancillary staff members, with as much or as little direct physician involvement as desired. The system has proven to be both time effective and cost effective, and it provides important outcome information both at the program level and at the clinician level. RESULTS: After the pilot test, the staff at Baptist Memorial Hospital determined that the system met all initial objectives identified and recently adopted the system as an ongoing measure of quality patient care in the department of psychiatry.

Length of Stay↗
PubMed2001

Remarks and conclusions on ovarian cancer treatment.

Ovarian cancer is still the fourth cause of death by cancer among women and the most fatal among gynecological tumors. The purpose of this symposium has been to report and discuss the new developments in the treatment of patients with ovarian cancer, the majority of whom still present with advanced disease. It also tries to make clear to the participants what is evidence-based and what is not. Although the main topic of the symposium is advanced disease, this edition included some updated information on the treatment of early disease under the heading "is early disease really early"; the importance of screening and molecular approaches are highlighted. In addition studies reported in the literature on the role of chemotherapy versus no chemotherapy in high-risk patients with early ovarian cancer have been updated. The pace of new agent development has increased, and it would be helpful to have more efficient preclinical models and early phase-clinical trials to guide the selection of active agents for phase III evaluation. Reaching international consensus is a challenge, but offers the opportunity to test multiple regimens more efficiently against a single control population, rather than conducting multiple smaller studies with redundant internal controls. If indeed answers to the relevant questions are to be obtained more quickly, then a network of current national or international groups could potentially facilitate this.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Predictors of psychiatric disorders in liver transplantation candidates: logistic regression models.

This study has two goals. The first goal is to assess the prevalence of psychiatric disorders in orthotopic liver transplantation (OLT) candidates by means of standardized procedures because there has been little research concerning psychiatric problems of potential OLT candidates using standardized instruments. The second goal focuses on identifying predictors of these psychiatric disorders. One hundred sixty-five elective OLT candidates were assessed by our unit. Psychiatric diagnoses were based on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients also were assessed using the Hamilton Depression Rating Scale (HDRS) and the Spielberger Anxiety Index, State and Trait forms (STAI-X1 and STAI-X2). Severity of cirrhosis was assessed by applying Child-Pugh score criteria. Chi-squared and general linear model analysis of variance were used to test the univariate association between patient characteristics and both clinical psychiatric diagnoses and severity of psychiatric diseases. Variables with P less than.10 in univariate analyses were included in multiple regression models. Forty-three percent of patients presented at least one psychiatric diagnosis. Child-Pugh score and previous psychiatric diagnoses were independent significant predictors of depressive disorders. Severity of psychiatric symptoms measured by psychometric scales (HDRS, STAI-X1, and STAI-X2) was associated with Child-Pugh score in the multiple regression model. Our data suggest a high rate of psychiatric disorders, particularly adjustment disorders, in our sample of OLT candidates. Severity of liver disease emerges as the most important variable in predicting severity of psychiatric disorders in these patients.

Adult↗
PubMed2002

The Circle of Security project: attachment-based intervention with caregiver-pre-school child dyads.

The Circle of Security intervention protocol is a 20-week, group-based, parent education and psychotherapy intervention designed to shift patterns of attachment-caregiving interactions in high-risk caregiver-child dyads to a more appropriate developmental pathway. All phases of the protocol, including the pre- and post-intervention assessments, and the intervention itself, are based on attachment theory and procedures, current research on early relationships, and object relations theory. Using edited videotapes of their interactions with their children, caregivers are encouraged: 1. to increase their sensitivity and appropriate responsiveness to the child's signals relevant to its moving away from to explore, and its moving back for comfort and soothing; 2. to increase their ability to reflect on their own and the child's behavior, thoughts and feelings regarding their attachment-caregiving interactions; and 3. to reflect on experiences in their own histories that affect their current caregiving patterns. In this paper we describe the conceptual background of the protocol, and the protocol itself. We then present a case study from our current data set of 75 dyads who have completed the protocol.

Adult↗
PubMed2006

A database and tool, IM Browser, for exploring and integrating emerging gene and protein interaction data for Drosophila.

BACKGROUND: Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins or genes as nodes linked by interactions. Several programs have been developed for graphical representation and analysis of interaction data, yet there remains a need for alternative programs that can provide casual users with rapid easy access to many existing and emerging data sets. DESCRIPTION: Here we describe a comprehensive database of Drosophila gene and protein interactions collected from a variety of sources, including low and high throughput screens, genetic interactions, and computational predictions. We also present a program for exploring multiple interaction data sets and for combining data from different sources. The program, referred to as the Interaction Map (IM) Browser, is a web-based application for searching and visualizing interaction data stored in a relational database system. Use of the application requires no downloads and minimal user configuration or training, thereby enabling rapid initial access to interaction data. IM Browser was designed to readily accommodate and integrate new types of interaction data as it becomes available. Moreover, all information associated with interaction measurements or predictions and the genes or proteins involved are accessible to the user. This allows combined searches and analyses based on either common or technique-specific attributes. The data can be visualized as an editable graph and all or part of the data can be downloaded for further analysis with other tools for specific applications. The database is available at http://proteome.wayne.edu/PIMdb.html CONCLUSION: The Drosophila Interactions Database described here places a variety of disparate data into one easily accessible location. The database has a simple structure that maintains all relevant information about how each interaction was determined. The IM Browser provides easy, complete access to this database and could readily be used to publish other sets of interaction data. By providing access to all of the available information from a variety of data types, the program will also facilitate advanced computational analyses.

Database Management Systems↗
PubMed2002

Denny-Brown, Wilson's disease, and BAL (British antilewisite [2,3-dimercaptopropanol]).

In 1951 Denny-Brown and Porter described the successful treatment of Wilson's disease using the chelating agent British antilewisite. The presentation of their results both at meetings and in print changed the traditional view of neurology from a descriptive to an interventional discipline using treatments based on the underlying biochemical disorder. The authors review the importance of these reports and provide edited digital versions of the films Denny-Brown made of the five patients described in the initial reports.

Dimercaprol↗