Prolongation of clozapine-induced granulocytopenia associated with olanzapine.
Explore the source record for details and available documents.
Agranulocytosis↗
Biomedical subjects
S Altman
Publications and source records attributed to S Altman.
The protein cofactor allows the sequence of an RNase P ribozyme to diversify by maintaining the catalytically active structure of the enzyme.
To study the effect proteins have on the catalysis and evolution of RNA enzymes, we simulated evolution of RNase P catalytic M1 RNA in vitro, in the presence and absence of its C5 protein cofactor. In the presence of C5, functional M1 sequence variants (not catalytically active in the absence of C5) were selected in addition to those identical to M1. C5 maintains the catalytically active structure of the variants and allows for an enhanced spectrum of M1 molecules to function in the context of a ribonucleoprotein (RNP) complex. The generation of an RNP enzyme, requiring both RNA and protein components, from a catalytically active RNA molecule has implications for how modern RNP complexes evolved from ancestral RNAs.
Bacterial Proteins↗
Labor legislation report.
Explore the source record for details and available documents.
Contract Services↗
Labor legislation.
Explore the source record for details and available documents.
Collective Bargaining↗
Arbitrator upholds RN's refusal to work unsafe assignment.
Explore the source record for details and available documents.
Clinical Competence↗
What's arbitration?
Explore the source record for details and available documents.
Collective Bargaining↗
Obstetric complications and age-related changes in brain morphology in schizophrenia.
Birth problems can lead to changes in brain morphology in the general population and an increased prevalence of both birth problems and altered brain morphology are found in patients with schizophrenia. The purpose of this study was to test the hypothesis that these two findings are related. Birth history and the size of ventricular and sulcal spaces from nine regions of the brain were assessed in 80 male subjects with schizophrenia. No differences were found between patients with and those without a history of birth problems for the size of any brain space; however, ventricular size increased significantly with age in patients who had no birth complications but not in patients with a history of birth problems. The size of cortical sulci increased with age in patients with and those without a history of birth problems. These results suggest that region-specific rates of change in size may identify clinically meaningful patients subgroups.
Adolescent↗
The RNA subunit of ribonuclease P from the zebrafish, Danio rerio.
A simple strategy has been devised to identify the gene encoding the RNA subunit of RNase P from the zebrafish, Danio rerio. The sequence obtained by amplification of genomic DNA with primers based on sequences common to two other vertebrates was confirmed by reverse transcription and amplification of RNA from a partially purified preparation of the holoenzyme. The 5' and 3' ends were determined by cyclizing the RNA, followed by reverse transcription and sequencing across the ligated RNA junction. The zebrafish sequence is 63% identical to that of Xenopus laevis nuclear RNase P RNA and 69% identical to the human RNase P RNA. A consensus secondary structure was constructed based on these nucleotide identities and on the many compensatory base changes in several regions among these three RNAs. The strategy used to obtain the zebrafish sequence should be useful in deriving analogous gene sequences from diverse classes of eukaryotes.
Animals↗
Requirements for cleavage by a modified RNase P of a small model substrate.
M1 RNA, the catalytic RNA subunit of RNase P from Escherichia coli, has been covalently linked at its 3' terminus to oligonucleotides (guide sequences) that guide the enzyme to target RNAs through hybridization with the target sequences. These constructs (M1GS RNAs) have been used to determine some minimal features of model substrates. As few as 3 bp on the 3' side of the site of cleavage in a substrate complex and 1 nt on the 5' side are required for cleavage to occur. The cytosines in the 3' terminal CCA sequence of the model substrates are important for cleavage efficiency but not cleavage site selection. A purine (base-paired or not) at the 3' side of the cleavage site is important both for cleavage site selection and efficiency. M1GS RNAs provide both a simple system for characterization of the reaction governed by M1 RNA and a tool for gene therapy.
Base Sequence↗
Mapping in three dimensions of regions in a catalytic RNA protected from attack by an Fe(II)-EDTA reagent.
The accessibility of the ribose groups in the phosphodiester chain of M1 RNA, the catalytic subunit of ribonuclease P from Escherichia coli, has been probed with an Fe(II)-EDTA reagent when the RNA is alone in solution, when it is in a complex with a tRNA precursor substrate, and when it is in the holoenzyme complex with its cofactor, C5 protein. The regions found to be protected under these various conditions, as well as those previously identified in other chemical probing experiments, have been mapped on a three-dimensional working model of M1 RNA and are generally compatible with the previously proposed placement of the substrate on the enzyme and with previous data and inferences regarding the interactions of C5 protein with M1 RNA. On the basis of the accessibilities of the C(4') atoms, refinements have been introduced in the model to accommodate the Fe(II)-EDTA protection data. The protein cofactor makes contact with several helical regions of the catalytic RNA on the opposite side of the surface to which substrates bind.
Bacterial Proteins↗
Cleavage by RNase P of gene N mRNA reduces bacteriophage lambda burst size.
RNase P, an enzyme essential for tRNA biosynthesis, can be directed to cleave any RNA when the target RNA is in a complex with a short, complementary oligonucleotide called an external guide sequence (EGS). RNase P from Escherichia coli can cleave phage lambda N mRNA in vitro or in vivo when the mRNA is in a complex with an EGS. The EGS can either be separate from or covalently linked to M1 RNA, the catalytic RNA subunit of RNase P. The requirement for Mg2+ in the reaction in vitro is lower when the EGS is covalently linked to M1 RNA. Substrates made of DNA can also be cleaved by RNase P in vitro in complexes with RNA EGSs. When either kind of EGS construct is used in vivo, burst size of phage lambda is reduced by > or = 40%. Reduction in burst size depends on efficient expression of the EGS constructs. The product of phage lambda gene N appears to function in a stoichiometric fashion.
Bacteriophage lambda↗
Artificial regulation of gene expression in Escherichia coli by RNase P.
Plasmids encoding various external guide sequences (EGSs) were constructed and inserted into Escherichia coli. In strains harboring the appropriate plasmids, the expression of fully induced beta-galactosidase and alkaline phosphatase activity was reduced by more than 50%, while no reduction in such activity was observed in strains with non-specific EGSs. The inhibition of gene expression was virtually abolished at restrictive temperatures in strains that were temperature-sensitive for RNase P (EC 3.1.26.5). Northern blot analysis showed that the steady-state copy number of EGS RNAs was several hundred per cell in vivo. A plasmid that contained a gene for M1 RNA covalently linked to a specific EGS reduced the level of expression of a suppressor tRNA that was encoded by a separate plasmid. Similar methods can be used to regulate gene expression in E. coli and to mimic the properties of cold-sensitive mutants.
Base Sequence↗
Characterization of RNA with unusual electrophoretic mobility from tissues of patients with Crohn's disease.
RNAs from tissues of patients with Crohn's disease that migrate off the diagonal in a two-dimensional gel electrophoresis system were partially characterized. One of the RNA species was a discrete cleavage product of region V2-9 of 28S rRNA; another is a conformer or variant of 5.8S rRNA; and a third is a mixture of unidentified fragments with mobility similar to that of 7S RNA. The yield of these species from resected tissue and their visualization by silver staining was very sensitive to the details of the preparative procedure. No evidence of viroid-like RNA was found within the range of molecular sizes (< 7S) that we examined.
Adenocarcinoma↗
Inhibition of viral gene expression by the catalytic RNA subunit of RNase P from Escherichia coli.
The catalytic RNA subunit (M1 RNA) of RNase P from Escherichia coli has been converted to an endoribonuclease that specifically cleaves the mRNA that encodes thymidine kinase (TK) of herpes simplex virus 1 (HSV-1). Covalent attachment to the 3' end of M1 RNA of a sequence complementary to TK mRNA results in very efficient cleavage of the target RNA in vitro. This reaction can be stimulated by proteins extracted from both E. coli and HeLa cells. When mouse cells in culture that express the novel RNA construct are infected with HSV-1, the levels of both TK mRNA and protein are reduced by approximately 80% as compared with cells that either do not express the novel RNA construct or express constructs with certain deletions that are known to abolish the catalytic activity of M1 RNA.
Animals↗
Scoping out 1995. How experts see the health care year unfolding. Interview by Terese Hudson.
In this issue, we look at the business side of health care from two different vantage points. First, how will health care fare in 1995 in the context of the overall economy? We've gathered a panel of economic experts to make predictions. Their conclusions? In general, providers won't benefit from a probable upturn in the broader economy.
Data Collection↗
Substrate recognition by human RNase P: identification of small, model substrates for the enzyme.
RNase P from HeLa cells can efficiently cleave tRNA precursor molecules in vitro but cannot cleave potential substrates from which the D, anticodon and variable loops and stems of the tRNA moiety have all been removed. However, molecules from which the latter subdomains have been removed individually do serve as substrates. We show here that molecules that contain only a 5' leader sequence, the acceptor stem and the T stem and loop of the tRNA domain, and a bulge as small as one nucleotide downstream from nucleotide 7 in the tRNA sequence at the junction of the two stems, can serve as substrates for human RNase P. The identity of the nucleotide in the bulge is important in determining both the efficiency of the cleavage and the conformation of the substrate and/or the enzyme-substrate complex. We also show that the human enzyme locates the appropriate site for cleavage of its substrates in part by 'measuring' the length of the helices in the acceptor and T stems in both model and natural substrates.
Base Sequence↗
Regional cortical anatomy and clozapine response in refractory schizophrenia.
Regional measures of cortical sulcal and ventricular enlargement on computed tomography scan were studied in a clinical sample of patients treated with clozapine. Cortical sulci were significantly enlarged in clozapine nonresponders compared to responders. The Clinical Global Impressions score at discharge was related to the size of the posterior frontal and lateral temporal sulci, with large sulci predicting a poorer response to clozapine treatment.
Adult↗
Obstetric complications and severity of illness in schizophrenia.
A history of obstetric complications (OCs) is common in schizophrenia and may lead to a severe form of the disorder. In order to test this possibility, three questions were identified: (1) Is a history of OCs in schizophrenia common in patients with a severe form of illness? (2) Do patients with OCs have more impaired function, greater severity of illness, and poorer treatment outcome than those with no identified OCs? (3) Are OCs associated with an early age at onset of illness? Obstetric history, clinical indices of functioning, and illness severity were obtained for 83 severely ill patients with schizophrenia. The proportion of patients with a history of OCs was greater in this study than has been reported previously. Subjects with a history of OCs had better functioning than those with no OCs at the time of admission but no group differences were found at discharge. No difference in age at onset of illness was found between patients with and without an OC history.
Activities of Daily Living↗