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At least 937 records · Page 52Linked to original sources
PubMed1990

Package inserts for antihypertensive drugs: use by the patients and impact on adverse drug reactions.

In Belgium, all dispensed drugs are provided with package inserts. Traditional physician-orientated inserts are gradually being replaced by patient package inserts (PPIs). The present survey is focused on the use of inserts for antihypertensive drugs and their impact on the reported occurrence and attribution of adverse drug reactions (ADRs). A group of 28 general practitioners (GPs) from the Flemish part of Belgium collected data from 702 hypertensive patients. Each participating GP submitted a consecutive sample of his patients to an interview in the Spring 1989, when 25% of the antihypertensive specialties carried a PPI-version. 1049 prescriptions for antihypertensive drugs had been dispensed. Two thirds of the patients, mostly those with a higher educational level, had read the package inserts. PPIs accounted for 16% of the inserts, and they had not been read significantly more than the traditional inserts. Reporting by the patients of possible drug-related health problems (spontaneously + after having heard the items on a check-list) was not affected by reading the insert or by the type of insert. However, the PPI did bring about spontaneous reporting, especially by patients with a low educational level. Attribution of at least one health problem to the medication was not affected by reading in itself but by the type of insert. Attribution was higher when the patient had received a PPI, except in the case of highly educated patients. Spontaneous reporting and attribution of health problems to the medications prescribed was found more frequently among patients with higher education, who did not seem to need a PPI to recognize problems as being drug-related.

Antihypertensive Agents↗
PubMed1988

Bacteriophage lambda DNA packaging: a mutant terminase that is independent of integration host factor.

Lambda+ is able to grow in Escherichia coli cells lacking integration host factor (IHF), producing a burst of approximately 25% that produced in IHF+ cells. In vitro, however, we find that the lambda DNA packaging enzyme terminase is strongly dependent on IHF in both cos cleavage reactions and DNA packaging reactions. The cos59 mutation renders lambda dependent on IHF in vivo. The cos59 mutation is a deletion of 3 base pairs at the XmnI site in the cohesive end site (cos) of lambda. Variants of lambda cos59 that were able to grow in the absence of IHF were isolated and found to carry a mutation, called ms1, in the Nu1 gene, which codes for the small subunit of terminase. The Nu1ms1 mutation results in a change of the 40th amino acid of the Nu1 gene product from leucine to phenylalanine. The Nu1ms1 terminase was independent of IHF in packaging reactions in vitro. The results indicate that the mutation either renders terminase: (1) able to utilize some host protein other than IHF, or (2) totally independent of host factors.

Bacterial Proteins↗
PubMed1994

Postmortem validation of the automated coronary analysis (ACA) software package.

Goal of this study was to compare the quantitative coronary arteriographic (QCA) results obtained with the Philips DCI/ACA analytical software package with those from postmortem casts in an animal experimental setting. Standard digital coronary arteriograms were obtained from 6 mongrel dogs. After the imaging procedure, the dogs were sacrificed and casts were made of the coronary trees by filling the vessels with a mixture of radio-opaque barium and silicone gel at a fixed pressure of 100 mmHg. Vessel diameters were measured from the digital arteriograms at a total of 118 selected locations with the ACA package. Thin slices were cut from the casts at these same measurement locations and the areas of the cross sections were obtained by manual tracing of the outline of each slice in an approximately 40 x magnified image. From these cross-sectional areas, cast diameters were derived using the formula for circular cross-sections. Cast diameters ranged in size from 0.69 to 3.30 mm. The systematic error between the measurements was found to be 0.058 mm; (p < 0.015) and the standard deviation of the signed difference 0.255 mm; the correlation coefficient was r = 0.91. The largest error sources are supposed to be the slight differences in the selection of identical positions in the X-ray images and on the casts, and the 'out-of-plane' magnification for a number of vessel locations. This postmortem study demonstrates that the diameters of coronary vessels can be measured from digital arteriograms with the DCI/ACA package with a high degree of accuracy and precision.

Animals↗
PubMed1999

Compact chromatin packaging of inactive X chromosome involves the actively transcribed Xist gene.

The Xist gene responsible for X inactivation may take a unique chromatin structure because of exceptional expression from inactive X Chromosome, (Chr). We have examined differential chromatin packaging of the Xist gene region between active and inactive X Chr with a novel method consisting of the chromatin fractionation and allele-specific detection. Analysis of F1 heterozygous female mice from T(X;16)16H x MSM crosses and two cell clones derived from inter-subspecific F1 female mice demonstrated that the packaging level of the transcribed Xist region on inactive X Chr was as tight as that of the repressed Pgk-1 allele on the same chromosome. On the other hand, restriction endonuclease sensitivity assay of chromatin showed that the promoter region, but not transcribed regions, of the transcribed Xist allele retained accessibility to nucleases. These results may suggest a cis-element(s) in a regulatory region of the Xist gene to prevent the transcriptionally inhibitory effect of the chromatin packaging.

Animals↗
PubMed2005

Inducible vesicular stomatitis virus (VSV) L cell line for packaging of recombinant VSV.

Recently, recombinant vesicular stomatitis viruses (VSV) have been developed as high-level expression vectors which serve as effective vaccine vectors in animals. An ideal approach for VSV vector production would be the development of stable packaging cell lines that can produce vector particles without transfection step. In this report, we describe generation of an inducible cell line that expresses the VSV polymerase gene (L) under the control of the reverse tetracycline-controlled transactivator (rtTA) system as a first step to make VSV-based packaging cell lines. Integrated polymerase (L) gene was controlled by an rtetR-dependent promoter in the rtTA-producing BHK cell line. When the cell lines were cultured in the presence of tet (tetracycline) or tetracycline derivative doxycycline, the recombinant VSV and wild type VSV were replicated, whereas in the absence of tet or tetracycline derivative doxycycline, the recombinant VSV was not replicated. Viral supernatants were harvested, diluted, and monitored by plaque assay for the presence of infectious VSV. Plaques of VSV containing an additional sequence encoding the EGFP protein allowed rapid detection of infection. Our results suggest wide applications of other surrogate viruses based on VSV. The availability of stable packaging cell lines represents a step toward the use of a VSV vector delivery system that can allow scale-up production of vector-stocks for gene therapy.

Animals↗
PubMed1989

Effectiveness of matched, mismatched, and package treatments of depression.

The three purposes of this study were: (a) to determine if treatment that is matched to a depressed subject's problematic behavioral response class (irrational cognitions, social skills problems, few pleasant events) is more effective in alleviating depression than is mismatched treatment; (b) to determine if a package treatment is as effective as or more effective than a matched treatment and more effective than a mismatched treatment in alleviating depression; and (c) to determine if a specific treatment produces more changes in its logically-related response class than in logically-unrelated response classes. Nine depressed women were assigned to one of three multiple baseline designs across subjects; subjects in each design received, respectively, matched, mismatched, or a package treatment. Results strengthened two hypotheses, that matched treatment and package treatment are both effective in alleviating depression. Specific treatments did not, however, differentially affect their logically-related response classes.

Adult↗
PubMed1988

Two level entry concept for analog digital conversion package: usage as blackbox or toolkit.

Analog/Digital conversion of up to 16 channels can be set up and executed interactively with sampling rates individually adjusted for each channel. Additionally, asynchron and parallel digital I/0 is provided, including the possibility of triggering the beginning and the end of data acquisition on an external TTL signal. For non-experienced personnel the package can be run fully interactively with help-menus. Conversely, the experienced user can skip the menu level and directly access the A/D conversion card at the programmers' level in FORTRAN, BASIC or PASCAL. This two level approach considerably enhances the versatility of the package. Data structures in memory and on disk are the same for both levels. Thus, data acquired in menu mode can be compatibly accessed and evaluated from the menu--as well as the programmers' level. Furthermore, a concept is presented for a most efficient and convenient transfer of pre-processed data onto an IBM-mainframe for further analysis in SAS. This transfer scheme allows for continued transparency of the data files, should--for technical reasons or due to changes in the type of data acquired--changes or upgradings of the A/D conversion software become necessary. The package is available for IBM-XT/AT personal computers.

Analog-Digital Conversion↗
PubMed1981

Simulation package for multiple intravenous infusions of two compartment pharmacokinetic drugs.

A program is presented to simulate the blood concentrations of two compartment pharmacokinetic drugs following multiple or intermittent constant rate intravenous infusions. The package requires the data input of some two compartment parameters, the rates and lengths of the infusions, and provides blood concentration-time predictions utilizing the principle of superposition. A unique feature of the package is the graphical plotting option, which displays the entire simulation all at once. The package was developed on a 48 000 byte Radio Shack TRS-80 microcomputer. The interpreter used was Radio Shack TRS-80 Level II Basic. This program is also compatible with TRS-80 Level III Basic. Approximately 5300 bytes of memory are occupied by the program with another 500-1500 bytes being necessary for data and results.

Computers↗
PubMed1986

Control of Rous sarcoma virus RNA translation and packaging by the 5' and 3' untranslated sequences.

A cytopathic mutant of Rous sarcoma virus-PrB was isolated and shown to have two large deletions, which result in the junction of Gag sequences in P27 to the 5' end of Env, and in the loss of the Src gene. This replication-defective (rd) and transformation-defective (td) mutant can replicate in the presence of its helper, which is also td, but the viral particles produced are poorly infectious. Most of the virions do not contain viral RNA, and the mutant RNA accumulates in infected cells, where it is poorly translated and packaged. Molecular clones of the mutant, of its helper and of a PrBtd strain were obtained in lambda-EMBL3, characterized, shown to be biologically active by transfection assays and sequenced. Nucleotide sequence comparisons indicate that the strong ribosome-binding site of Rous sarcoma virus RNA, responsible for the efficient RNA translation in vivo and in vitro, is mutated in PrB-(HM) mutant RNA; this causes the inhibition of RNA translation, as demonstrated by translation competition experiments using virus RNA made in vitro that carries the original or the mutated ribosome-binding site. In addition, an insertion present at the 3' end of both the mutant and the helper RNA, but absent in PrBtd RNA, is probably responsible for the inhibition of RNA packaging. Finally, these data are discussed in the light of a model of a 5'----3' Rous sarcoma virus RNA structure leading to a circular RNA molecule, which has implications in RNA translation, packaging and reverse transcription.

Autoradiography↗
PubMed1987

Characterization of the bacteriophage T3 DNA packaging reaction in vitro in a defined system.

The bacteriophage T3 DNA packaging system in vitro defined here is composed of purified proheads and two non-capsid proteins, the products of genes 18 and 19 (gp18 and gp19). In this system, a precursor complex (50 S complex) accumulates in the presence of adenosine 5'-O-(3'-thiotriphosphate) (ATP-gamma-S), a non-hydrolyzable analog of ATP. The 50 S complex is converted to a filled head in the presence of ATP. The conversion of the 50 S complex, formed by preincubation with ATP-gamma-S, to the mature head proceeds in a synchronous manner after the addition of ATP. The lag time for formation of mature heads from the 50 S complex is 1.8, 4.5 and 6.8 minutes at 30, 25 and 20 degrees C, respectively. DNA is translocated into the capsid at a constant rate of 5.7 x 10(3) base-pairs per minute at 20 degrees C. The conversion of the 50 S complex to the mature head exhibits a sigmoidal relationship with respect to the concentration of ATP, the concentration for half-maximal activity being about 20 microM. The transition of the prohead to the expanded capsid occurs at 20 degrees C at one minute 40 seconds after the initiation of DNA translocation, when one-fourth of the genome has been packaged into a prohead. At the same time, the capsid-DNA complex becomes stable to high concentrations of salt. When DNA translocation is interrupted by the addition of ATP-gamma-S, packaged DNA exists at 0 degrees C as well as at 20 degrees C but the exit of DNA stops after one-third of the genome is inside the capsid. After exit, DNA is retranslocated into the expanded capsid by the addition of ATP at a rate of about 5.7 x 10(3) base-pairs per minute at 20 degrees C. The decrease in concentration of ATP interrupts DNA translocation into the capsid but does not induce DNA exit. Interrupted DNA translocation may be reinitiated by the addition of ATP. DNA exit is not induced by the addition of ATP-gamma-S to mature heads or partially filled heads pretreated with DNase.

Adenosine Triphosphate↗
PubMed1991

The last duplex base-pair of the phage lambda chromosome. Involvement in packaging, ejection and routing of lambda DNA.

cosN is the site at which the bacteriophage lambda DNA packaging enzyme, terminase, introduces staggered nicks to generate the cohesive ends of mature lambda chromosomes. Genetic and molecular studies show that cosN is recognized specifically by terminase and that effects of cosN mutations on lambda DNA packaging and cosN cleavage are well correlated. Mutations affecting a particular base-pair of cosN are unusual in being lethal in spite of causing only a moderate defect in cosN cleavage and DNA packaging. The particular base-pair is the rightmost duplex base-pair in mature chromosomes, at position 48,502 in the numbering system of Daniels et al; herein called position - 1. A G.C to T.A transversion mutation at position - 1, called cosN - 1T, reduces the particle yield of lambda fivefold, and the particles formed are not infectious. lambda cosN - 1T particles have wild-type morphology, and contain chromosomes that have normal cohesive ends. The chromosomes of lambda cosN - 1T particles, like the chromosomes of lambda + particles, are associated with the tail. lambda cosN - 1T particles, in spite of being normal structurally, are defective in injection of DNA into a host cell. Only approximately 25% of lambda cosN - 1T particles are able to eject DNA from the capsid in contrast to 100% for lambda +. Furthermore, for the 25% that do eject, there is a further injection defect because the ejected lambda cosN - 1T chromosomes fail to cyclize, in contrast to the efficient cyclization found for wild-type chromosomes following injection. The cosN - 1T mutation has no effect on Ca2+ mediated transformation by lambda DNA, indicating that the effect of the mutation on DNA fate is specific to the process of DNA injection. Models in which specific DNA : protein interactions necessary for DNA injection, and involving the rightmost base-pair of the lambda chromosome, are considered.

Bacteriophage lambda↗
PubMed1992

Bacteriophage P1 genes involved in the recognition and cleavage of the phage packaging site (pac).

The packaging of bacteriophage P1 DNA is initiated by cleavage of the viral DNA at a specific site, designated pac. The proteins necessary for that cleavage, and the genes that encode those proteins, are described in this report. By sequencing wild-type P1 DNA and DNA derived from various P1 amber mutants that are deficient in pac cleavage, two distinct genes, referred to as pacA and pacB, were identified. These genes appear to be coordinately transcribed with an upstream P1 gene that encodes a regulator of late P1 gene expression (gene 10). pacA is located upstream from pacB and contains the 161 base-pair pac cleavage site. The predicted sizes of the PacA and PacB proteins are 45 kDa and 56 kDa, respectively. These proteins have been identified on SDS-polyacrylamide gels using extracts derived from Escherichia coli cells that express these genes under the control of a bacteriophage T7 promoter. Extracts prepared from cells expressing both PacA and PacB are proficient for site-specific cleavage of the P1 packaging site, whereas those lacking either protein are not. However, the two defective extracts can complement each other to restore functional pac cleavage activity. Thus, PacA and PacB are two essential bacteriophage proteins required for recognition and cleavage of the P1 packaging site. PacB extracts also contain a second P1 protein that is encoded within the pacB gene. We have identified this protein on SDS-polyacrylamide gels and have shown that it is translated in the same reading frame as is PacB. Its role, if any, in pac cleavage is yet to be determined.

Amino Acid Sequence↗
PubMed1992

Genetic analysis of mutations affecting terminase, the bacteriophage lambda DNA packaging enzyme, that suppress mutations in cosB, the terminase binding site.

Terminase, the DNA packaging enzyme of phage lambda, binds to lambda DNA at a site called cosB, and introduces staggered nicks at an adjacent site, cosN, to generate the cohesive ends of virion lambda DNA molecules. Terminase also is involved in separation of the cohesive ends and in binding the prohead, the empty protein shell into which lambda DNA is packaged. Terminase is a DNA-dependent ATPase, and both subunits, gpNu1 and gpA, have ATPase activity. cosB contains a series of gpNu1 binding sites, R3, R2 and R1; between R3 and R2 is a binding site, I1, for integration host factor (IHF), the Escherichia coli DNA bending protein. In this work, a series of mutations in Nu1 have been isolated as suppressors of cosB mutations. One of the Nu1 mutations is identical to the previously described Nu1ms1/ohm1 mutation predicted to cause the change L40F in the 181 amino acid-long gpNu1. Three other Nu1 missense mutations, the Nu1ms2 (L40I), ms3 (Q97K) and ms4 (A92G) mutations, have been isolated; the relative strengths of suppression of cosB mutations by the Nu1ms mutations are: ms1 > ms2 > ms3 > ms4. The Nu1 missense mutations all affect amino acid residues that lie outside of the putative helix-turn-helix DNA binding motif of gpNu1. The Nu1ms1 and Nu1ms2 mutations alter an amino acid residue (L40) that lies directly between two segments of gpNu1 proposed to be involved in ATP binding and hydrolysis; thus these mutations are likely to alter the gpNu1 ATP-binding site. The Nu1ms3 and Nu1ms4 mutations both affect amino acid residues in the central region of gpNu1 that is predicted to form a hydrophilic alpha-helix. To explain how the Nu1ms mutations suppress cosB defects, models involving alterations of the DNA binding and/or catalytic properties of terminase are considered. The results also indicate that terminase occupancy of a single gpNu1 binding site (R3) is necessary and sufficient for the efficient initiation of DNA packaging; the Nu1ms1, ms2 and ms3 mutations permit IHF-independent plaque formation by a phage lacking R2 and R1.

Amino Acid Sequence↗
PubMed1989

The treatment of somatization: evaluation of a teaching package with general practice trainees.

A teaching package is described which aims to improve the management of somatization by general practice trainees. The package comprises a training videotape in which a model (described in the preceding paper) is demonstrated, together with material for paired role-play of new skills and small group videofeedback of consultations. Evaluation of the teaching package reveals that the skills can be effectively learned.

Education, Medical, Continuing↗
PubMed1984

In vitro packaging of mature phage DNA by Salmonella phage P22.

Mature, headful-sized DNA extracted from the Salmonella phages P22 and L, and P22/L-hybrid phages can be encapsulated in vitro by means of a packaging system for exogenous DNA. The probability of packaging reaches about 10(-3) per headful-sized molecule. The absence of in vitro recombination was demonstrated, to eliminate the possibility that such a process had created concatemers. The endonucleolytic cut at the pac site, which initiates sequential packaging in vivo, does not occur with the mature DNA substrate in vitro. The position of pac on the molecule is not important but the pac-recognizing phage protein gp3 is indispensable for in vitro encapsulation.

DNA, Viral↗
PubMed1991

Characterization of recombinant helper retroviruses from Moloney-based vectors in ecotropic and amphotropic packaging cell lines.

We have characterized the recombinant replication-competent retrovirus (RCV) arising from p delta N2-derived vectors in the packaging cell lines psi 2 (ecotropic) and PA317 (amphotropic). Detailed restriction patterns and sequence of the envelope region of these RCVs has indicated that they arose from recombination events between the virus plasmids used to create the packaging cell line and the vectors. There was no evidence of recombination involving endogenous murine retroviral sequences in the packaging cell line or in transduced hematopoietic cells. In addition, we have confirmed that the mutation of the start codon of the pXM5(N2) derivatives gag+ sequence drastically decreased the occurrence of RCV production. These results offer encouragement that the risk of RCV production can be adequately decreased in gene therapy applications of defective retrovirus vectors.

Adenosine Deaminase↗
PubMed1991

Analysis of interactions among factors involved in the bacteriophage T3 DNA packaging reaction in a defined in vitro system.

During head assembly of phage T3, DNA is packaged into the cavity of a preformed protein shell, called the prohead, with the aid of noncapsid, packaging proteins, the products of genes 18 and 19 (gp18 and gp19). gp18 and gp19 separately form complexes with DNA and proheads, respectively. These complexes associate to form a precursor which can be converted to filled heads by the addition of ATP. Interactions among factors involved in DNA packaging were analyzed. In the presence of ATP, gp19 formed functional complexes with proheads. Formation of gp19-prohead complex showed a sigmoidal dependence on ATP concentration with a half maximal concentration of about 7.5 microM. Six molecules of gp19 bound to the prohead at a saturating amount of gp19. gp19 did not bind to proheads lacking the connector of gp8 (8- prohead). In the absence of ATP, proheads were inactivated by gp19. The gp19-prohead complexes formed in the absence of ATP contained 20-30 gp19 molecules per prohead and formed multimeric aggregates. 8- proheads did not bind gp19 and did not form such aggregates even in the absence of ATP. From these results, we conclude that 6 molecules of gp19 bind to the gp8 connector structure in the portal vertex of the prohead. The cleavage patterns of gp19 by several proteases were altered by the addition of ATP, indicating that ATP induces a conformational change in gp19, gp18 bound only to linear, duplex DNA.

Adenosine Triphosphate↗
PubMed1991

In vitro packaging of the bacteriophage phi 6 ssRNA genomic precursors.

Bacteriophage phi 6 contains three segments of double-stranded RNA within a nucleocapsid. Plasmids containing cDNA copies of the large genomic segment direct the synthesis of viral proteins that assemble into procapsids in Escherichia coli or Pseudomonas phaseolicola. These structures are dodecahedral assemblages of proteins P1, P2, P4, and P7. We report in this paper that these particles are capable of packaging viral single-stranded plus-sense RNA in vitro. The packaging reaction requires the presence of ATP or dATP. Synthesis of minus strands takes place within this filled procapsid in the presence of all four nucleoside triphosphates. Packaged ssRNA is found to be protected from added ribonuclease.

Adenosine Triphosphate↗