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At least 289 records · Page 16Linked to original sources

PubMed2000

The ribosomal RNA processing machinery is recruited to the nucleolar domain before RNA polymerase I during Xenopus laevis development.

Transcription and splicing of messenger RNAs are temporally and spatially coordinated through the recruitment by RNA polymerase II of processing factors. We questioned whether RNA polymerase I plays a role in the recruitment of the ribosomal RNA (rRNA) processing machinery. During Xenopus laevis embryogenesis, recruitment of the rRNA processing machinery to the nucleolar domain occurs in two steps: two types of precursor structures called prenucleolar bodies (PNBs) form independently throughout the nucleoplasm; and components of PNBs I (fibrillarin, nucleolin, and the U3 and U8 small nucleolar RNAs) fuse to the nucleolar domain before components of PNBs II (B23/NO38). This fusion process is independent of RNA polymerase I activity, as shown by actinomycin D treatment of embryos and by the lack of detectable RNA polymerase I at ribosomal gene loci during fusion. Instead, this process is concomitant with the targeting of maternally derived pre-rRNAs to the nucleolar domain. Absence of fusion was correlated with absence of these pre-rRNAs in nuclei where RNA polymerase II and III are inhibited. Therefore, during X. laevis embryogenesis, the recruitment of the rRNA processing machinery to the nucleolar domain could be dependent on the presence of pre-rRNAs, but is independent of either zygotic RNA polymerase I transcription or the presence of RNA polymerase I itself.

Animals↗

PubMed1995

The Processes, Structures, and Outcomes of Care in Cardiac Surgery study protocol.

Recently, a growing interest has arisen in defining and measuring health care outcomes. Although outcome measures may be used as potential quality-of-care screens, outcomes cannot indicate directly how care might be improved. Thus, the Processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS) study was designed to investigate the linkages between the processes and structures of care with risk-adjusted outcomes for cardiac surgery care. Data are being collected on a comprehensive array of risk factors, processes, structures, and outcomes of care at 14 Veterans Affairs Medical Centers for this prospective, observational study. Approximately 6,000 cardiac surgery patients will be enrolled in this study over a 4.5-year period. Patient selection is based on a 6 workday rotating sampling frame with an oversampling of emergent patients. During the study, a register of all patients undergoing cardiac surgery at these centers is being maintained to assess the overall context of patient recruitment. The study will continue to enroll patients through December 1996. Major study end points extend beyond traditional measures of 30-day mortality and morbidity to encompass more innovative intermediate outcome measures, including changes in physical functional status and health-related quality of life.

Aged↗

PubMed1992

Interhemispheric and intrahemispheric control of emotion: a focus on unilateral brain damage.

Neocortical contributions to emotional processing are discussed. First, parameters critical to the neuropsychological study of emotion are examined: interhemispheric (right, left) and intrahemispheric (anterior, posterior) factors, processing mode (expression, perception), and communication channel (facial, prosodic, lexical). Second, neuropsychological theories of emotion are described: right-hemisphere and valence hypotheses. Third, experimental studies of right-brain-damaged, left-brain-damaged, and normal adults are reviewed, on the basis of mode and channel, with a focus on stroke. Findings support right cerebral hemispheric dominance for emotion, regardless of valence and channel, and are more consistent for perception than expression. When lesion site is a factor, posterior sites are important for perception and anterior ones for expression. Finally, clinical implications are suggested for aphasia rehabilitation and for assessment of affect in neurological disorders.

Adult↗

PubMed2002

Floating dosage systems in drug delivery.

The identification of new diseases and the resistance shown toward existing drugs calls for the introduction of new therapeutic molecules. In response, a large number of chemical entities have been introduced, of which some have absorption over the entire gastrointestinal tract (GIT), some have absorption windows (i.e., absorption sites, especially the upper part of the small intestine), and some have poor solubility in intestinal media altogether. The drugs belonging to the second and third categories, and the drugs required for local action in the stomach, require a specialized delivery system. All the above requirements can be met and effective delivery of the drugs to the absorption window, for local action and for treatment of gastric disorders such as gastro-esophageal reflux, can be achieved by floating dosage systems (FDS). To date, a number of FDS involving various technologies, carrying their own advantages and limitations, were developed, such as single- and multiple-unit hydrodynamically balanced systems (HBS), single- and multiple-unit gas-generating systems, hollow microspheres, and raft-forming systems. Various factors such as gastrointestinal physiology, dosage form characteristics, and patient-related factors control the behavior of FDS. This review discusses the anatomy and physiology of the stomach, the gastric emptying process, factors affecting the gastric retention of dosage forms, and various techniques adopted in the development of FDS.

Animals↗

PubMed1995

Shared functions in vivo of a glycosyl-phosphatidylinositol-linked aspartyl protease, Mkc7, and the proprotein processing protease Kex2 in yeast.

The MKC7 gene was isolated as a multicopy suppressor of the cold-sensitive growth phenotype of a yeast kex2 mutant, which lacks the protease that cleaves pro-alpha-factor and other secretory proproteins at pairs of basic residues in a late Golgi compartment in yeast. MKC7 encodes an aspartyl protease most closely related to product of the YAP3 gene, a previously isolated multicopy suppressor of the pro-alpha-factor processing defect of a kex2 null. Multicopy MKC7 suppressed the alpha-specific mating defect of a kex2 null as well as multicopy YAP3 did, but multicopy YAP3 was a relatively weak suppressor of kex2 cold sensitivity. Overexpression of MKC7 resulted in production of a membrane-associated proteolytic activity that cleaved an internally quenched fluorogenic peptide substrate on the carboxyl side of a Lys-Arg site. Treatment with phosphatidylinositol-specific phospholipase C shifted Mkc7 activity from the detergent to the aqueous phase in a Triton X-114 phase separation, indicating that membrane attachment of Mkc7 is mediated by a glycosyl-phosphatidylinositol anchor. Although disruption of MKC7 or YAP3 alone resulted in no observable phenotype, mkc7 yap3 double disruptants exhibited impaired growth at 37 degrees C. Disruption of MKC7 and YAP3 in a kex2 null mutant resulted in profound temperature sensitivity and more generalized cold sensitivity. The synergism of mkc7, yap3, and kex2 null mutations argues that Mkc7 and Yap3 are authentic processing enzymes whose functions overlap those of Kex2 in vivo.

Amino Acid Sequence↗

PubMed1975

Activation of bovine factor X (Stuart factor): conversion of factor Xaalpha to factor Xabeta.

Bovine factor X (molecular weight 55,100) is a blood coagulation factor present in plasma in a precursor or zymogen form. It is a glycoprotein which has been isolated as a two-chain structure held together by one or more disulfide bonds. During the coagulation process, factor X is converted to a serine protease by the hydrolysis of a specific peptide bond in the amino-terminal region of the heavy chain. This cleavage occurs between Arg-51 and Ile-52, giving rise to factor Xaalpha (molecular weight 45,300) and an activation peptide (molecular weight 9500). Factor Xaalpha is then converted to factor Xabeta (molecular weight 42,600) by hydrolysis of a second specific peptide bond in the carboxyl-terminal region of the heavy chain. This cleavage occurs between Arg-290 and Gly-291, giving rise to a second glycopeptide (molecular weight 2700). Factor Xaalpha and factor Xabeta have equivalent coagulant activity, indicating that the cleavage of the second peptide bond is unrelated to the activation process.

Amino Acid Sequence↗

PubMed1993

Current perspectives on the dissolution stability of solid oral dosage forms.

Dissolution stability (i.e., retention of the dissolution characteristics of a solid oral dosage form from the time of manufacture up to its expiration date) is a critical parameter from the standpoint of quality control, regulatory compliance, and impact on the bioavailability of the product. Significant changes in the in vitro release profiles of a drug product during storage may alter its bioavailability. Factors that affect the dissolution stability of a product during aging include formulation components (active drug, excipients, and coating materials), processing factors, storage conditions, and packaging. The role of each of these factors in promoting changes in dissolution in both immediate-release and modified-release products is dependent on the product and has to be evaluated on a case-by-case basis. Although data obtained under accelerated conditions of storage are not useful in predicting the dissolution shelf-life of the product under ambient conditions, they are of value in assessing the "ruggedness" of the product and its ability to withstand the varied climatic conditions during transport, shipping, and storage. The clinical significance of alterations in the in vitro dissolution profiles that may occur during aging and strategies to avert and counteract such changes are discussed in the article.

Administration, Oral↗

PubMed1997

PCNA: structure, functions and interactions.

Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid metabolism as a component of the replication and repair machinery. This toroidal-shaped protein encircles DNA and can slide bidirectionally along the duplex. One of the well-established functions for PCNA is its role as the processivity factor for DNA polymerase delta and epsilon. PCNA tethers the polymerase catalytic unit to the DNA template for rapid and processive DNA synthesis. In the last several years it has become apparent that PCNA interacts with proteins involved in cell-cycle progression which are not a part of the DNA polymerase apparatus. Some of these interactions have a direct effect on DNA synthesis while the roles of several other interactions are not fully understood. This review summarizes the structural features of PCNA and describes the diverse functions played by the protein in DNA replication and repair as well as its possible role in chromatin assembly and gene transcription. The PCNA interactions with different cellular proteins and the importance of these interactions are also discussed.

Animals↗

PubMed2003

XRad17 is required for the activation of XChk1 but not XCds1 during checkpoint signaling in Xenopus.

The DNA damage/replication checkpoints act by sensing the presence of damaged DNA or stalled replication forks and initiate signaling pathways that arrest cell cycle progression. Here we report the cloning and characterization of Xenopus orthologues of the RFCand PCNA-related checkpoint proteins. XRad17 shares regions of homology with the five subunits of Replication factor C. XRad9, XRad1, and XHus1 (components of the 9-1-1 complex) all show homology to the DNA polymerase processivity factor PCNA. We demonstrate that these proteins associate with chromatin and are phosphorylated when replication is inhibited by aphidicolin. Phosphorylation of X9-1-1 is caffeine sensitive, but the chromatin association of XRad17 and the X9-1-1 complex after replication block is unaffected by caffeine. This suggests that the X9-1-1 complex can associate with chromatin independently of XAtm/XAtr activity. We further demonstrate that XRad17 is essential for the chromatin binding and checkpoint-dependent phosphorylation of X9-1-1 and for the activation of XChk1 when the replication checkpoint is induced by aphidicolin. XRad17 is not, however, required for the activation of XCds1 in response to dsDNA ends.

Amino Acid Sequence↗

PubMed1996

Factors responsible for the establishment of the body plan in the amphibian embryo.

A central topic of embryology is the establishment of the body plan during embryogenesis. Starting with maternal factors distributed in the early cleavage stages in distinct patterns and gradients cell-to-cell interactions including early embryonic induction result in the formation of mesoderm and the organizer area. While many facts are known about the role of growth factors like activin (closely related to the vegetalizing factor), processed Vg1, BMPs and FGF for mesoderm formation, the establishment of the central nervous system is not yet well understood. However, there is growing evidence that neural induction is a multistep process at the level of the dorsal mesoderm (organizer) and the reacting neuroectoderm. Therefore the existence of only one neuralizing factor is unlikely. We report about data that follistatin protein is not a direct neural inducer. Furthermore our comparative studies of Xenopus and Triturus exogastrulae indicate that planar signals are unlikely in the Triturus embryo (urodeles) during the early steps of neural induction. Vertical signals emanating from the chordamesoderm are essential for the terminal neuralization and regionalization of the central nervous system during gastrulation for both Xenopus and Triturus. The putative role of neuralizing factors and BMP/activin-like molecules for the stabilization or shift of neuroectoderm into different pathways of differentiation (epidermis or neural default state) is discussed.

Amphibians↗

PubMed1987

Cognitive constraints on ordering operations: the case of geometric analogies.

Many tasks (e.g., solving algebraic equations and running errands) require the execution of several component processes in an unconstrained order. The research reported here uses the geometric analogy task as a paradigm case for studying the ordering of component processes in this type of task. In solving geometric analogies by applying mental transformations such as rotate, change size, and add a part, the order of performing the transformations is unconstrained and does not in principle affect solution accuracy. Nevertheless, solvers may bring cognitive constraints with them to the analogy task that influence the ordering of the transformations. First, we demonstrate that solvers have a preferred order for performing mental transformations during analogy solution. We then investigate three classes of explanations for the preferred order, one based on general information processing considerations, another based on task-specific considerations, and a third based on individual differences in analogy ability. In the first and third experiments, college students solved geometric analogies requiring two or three transformations and indicated the order in which they performed the transformations. There was close agreement on nearly the same order for both types of analogies. In the second experiment, subjects were directed to perform pairs of transformations in the preferred or unpreferred order. Both speed and accuracy were greater for the preferred orders, thus validating subjects' reported orders. Ability differences were observed for only the more difficult three-transformation problems: High- and middle-ability subjects agreed on an overall performance order, but the highs were more consistent in their use of this order. Low-ability subjects did not consistently order the transformations for these difficult problems. The general information processing factor examined was working-memory load. A number of task factors have been shown to affect working-memory load during the solution of inductive reasoning problems. Of these, we chose to examine process difficulty. Because analogies are solved in working memory, performing more difficult transformations earlier may reduce working-memory load and facilitate problem solution. However, the observed performance order was not correlated with transformation difficulty. The first task-specific factor considered was that some transformations may be identified earlier, possibly because of perceptual salience, and that the performance order follows the identification order.(ABSTRACT TRUNCATED AT 400 WORDS)

Cognition↗

PubMed1998

Reconstitution of recombinant human replication factor C (RFC) and identification of an RFC subcomplex possessing DNA-dependent ATPase activity.

Replication factor C (RFC) is a five-subunit protein complex required for coordinate leading and lagging strand DNA synthesis during S phase and DNA repair in eukaryotic cells. It functions to load the proliferating cell nuclear antigen (PCNA), a processivity factor for polymerases delta and epsilon, onto primed DNA templates. This process, which is ATP-dependent, is carried out by 1) recognition of the primer terminus by RFC () binding to and disruption of the PCNA trimer, and then 3) topologically linking the PCNA to the DNA. In this report, we describe the purification and properties of recombinant human RFC expressed in Sf9 cells from baculovirus expression vectors. Like native RFC derived from 293 cells, recombinant RFC was found to support SV40 DNA synthesis and polymerase delta DNA synthesis in vitro and to possess an ATPase activity that was highly stimulated by DNA and further augmented by PCNA. Assembly of RFC was observed to involve distinct subunit interactions in which both the 36- and 38-kDa subunits interacted with the 37-kDa subunit, and the 40-kDa subunit interacted with the 36-kDa subunit-37-kDa subunit subcomplex. The 140-kDa subunit was found to require interactions primarily with the 38- and 40-kDa subunits for incorporation into the complex. In addition, a stable subcomplex lacking the 140-kDa subunit, although defective for DNA replication, was found to possess DNA-dependent ATPase activity that was not responsive to the addition of PCNA.

Adenosine Triphosphatases↗

PubMed1982

Factors affecting medication-order processing time.

The factors affecting medication-order processing time at one hospital were studied. The order processing time was determined by directly observing the time to process randomly selected new drug orders on all three work shifts during two one-week periods. An order could list more than one drug for an individual patient. The observer recorded the nature, location, and cost of the drugs ordered, as well as the time to process the order. The time and type of interruptions also were noted. The time to process a drug order was classified as six dependent variables: (1) total time, (2) work time, (3) check time, (4) waiting time I--time from arrival on the dumbwaiter until work was initiated, (5) waiting time II--time between completion of the work and initiation of checking, and (6) waiting time III--time after the check was completed until the order left on the dumbwaiter. The significant predictors of each of the six dependent variables were determined using stepwise multiple regression. The total time to process a prescription order was 58.33 +/- 48.72 minutes; the urgency status of the order was the only significant determinant of total time. Urgency status also significantly predicted the three waiting-time variables. Interruptions and the number of drugs on the order were significant determinants of work time and check time. Each telephone interruption increased the work time by 1.72 minutes. While the results of this study cannot be generalized to other institutions, pharmacy managers can use the method of determining factors that affect medication-order processing time to identify problem areas in their institutions.

Medication Systems, Hospital↗

PubMed1999

Return to work experience of injured workers in a case management program.

A major goal of case management programs is the worker's timely return to work. Few studies have examined return to work from the perspective of the injured worker. This article describes the findings from the case management evaluation that describe the return to work experience of workers who sustained catastrophic injuries, or who had secondary conditions or complications following the injury occurrence. Among the factors determined to affect the return to work experience were structural factors (i.e., psychosocial variables including job satisfaction and relationship with employer and coworkers, financial pressures, and system issues such as securing benefits) and process factors (i.e., interaction with service providers and with the workers' compensation system). Outcomes are described in terms of satisfaction with services and return to work.

Absenteeism↗

PubMed1994

Treatment process and relapse to opioid use during methadone maintenance.

A general framework for studying drug abuse treatment process factors is presented, and components are then used to predict relapse to opioid use during treatment in methadone maintenance. Major domains of the treatment process research framework include client variables at entry, program characteristics, treatment events, and client outcomes. The analyses rely on the use of proportional hazards models to identify significant outcome predictors in a sample of 590 methadone maintenance clients from 21 clinics in the Research Triangle Institute/Treatment Outcome Prospective Study (RTI/TOPS) data system who remained in treatment at least 3 months. The analyses were performed on the total sample and separately on clients from three groups of clinics classified on the basis of the distribution of client relapse rates and tenure in treatment. Relapse rates were related to dosage level, client monitoring with urinalyses, and methadone take-home privileges in some clinics, and hence, these time-varying treatment events were important factors in treatment outcomes. Even at entry to treatment, some measures were found to be related to how the client later performed during treatment. Finally, it was also found that the particular area of professional speciality of the staff making client diagnosis at intake and preparing treatment plans was associated with client outcomes.

Adult↗

PubMed1978

Explanatory model for the interaction of factors in the caries process.

The interaction of factors in the caries process has recently been discussed in a number of articles. Based on this, a new explanatory model has been constructed, consisting of an equilateral triangle with one of the apices on a horizontal line, along which dietary and oral hygiene habits are scaled. The triangle represents the total area of interaction. A horizontal line of resistance cuts off a lower part corresponding to the area within which caries does not occur. Through planogeometric calculations the remaining part of the triangle can be divided into areas, approximately corresponding to the relative caries values of various combinations of dietary and oral hygiene habits. The model has proved to be a useful instrument for demonstrating and creating an understanding of interactive processes among various groups of dental health personnel. The example presented is based on a pilot study of 55 4-year-old children in Malmö.

Child, Preschool↗

PubMed2001

Cleavage/polyadenylation factor IA associates with the carboxyl-terminal domain of RNA polymerase II in Saccharomyces cerevisiae.

The carboxyl-terminal domain (CTD) of the largest subunit of RNA polymerase II plays an important role in transcription and processing of the nascent transcript by interacting with both transcription and RNA processing factors. We show here that the cleavage/polyadenylation factor IA of Saccharomyces cerevisiae directly contacts CTD. First by affinity chromatography experiments with yeast extracts we demonstrate that the Rna15p, Rna14p, and Pcf11p subunits of this complex are associated with phosphorylated CTD. This interaction is confirmed for Rna15p by yeast two-hybrid analysis. Second, Pcf11p, but not Rna15p, is shown to directly contact phosphorylated CTD based on in vitro binding studies with recombinant proteins. These findings establish a direct interaction of cleavage/polyadenylation factor IA with the CTD. Furthermore, a quantitative analysis of transcription run-on performed on temperature-sensitive mutant strains reveals that the lack of either functional Rna14p or Pcf11p affects transcription termination more severely than the absence of a functional Rna15p. Moreover, these data reinforce the concept that CTD phosphorylation acts as a regulatory mechanism in the maturation of the primary transcript.

Amino Acid Sequence↗

PubMed2003

3' to 5' exonuclease activity of herpes simplex virus type 1 DNA polymerase modulates its strand displacement activity.

Using a minicircle DNA primer-template, the wild-type catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase (pol) was shown to lack significant strand displacement activity with or without its processivity factor, UL42. However, an exonuclease-deficient (exo(-)) pol (D368A) was capable of slow strand displacement. Although UL42 increased the rate (2/s) and processivity of strand displacement by exo(-) pol, the rate was slower than that for gap-filling synthesis. High inherent excision rates on matched primer-templates and rapid idling-turnover (successive rounds of excision and polymerization) of exo-proficient polymerases correlated with poor strand displacement activity. The results suggest that the exo activity of HSV-1 pol modulates its ability to engage in strand displacement, a function that may be important to the viability and genome stability of the virus.

Base Sequence↗