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At least 1,009 records · Page 56Linked to original sources
PubMed1998

Methylation of FrzCD defines a discrete step in the developmental program of Myxococcus xanthus.

Myxococcus xanthus is a gram-negative soil bacterium which undergoes fruiting body formation during starvation. The frz signal transduction system has been found to play an important role in this process. FrzCD, a methyl-accepting taxis protein homologue, shows modulated methylation during cellular aggregation, which is thought to be part of an adaptation response to an aggregation signal. In this study, we assayed FrzCD methylation in many known and newly isolated mutants defective in fruiting body formation to determine a possible relationship between the methylation response and fruiting morphology. The results of our analysis indicated that the developmental mutants could be divided into two groups based on their ability to show normal FrzCD methylation during development. Many mutants blocked early in development, i.e., nonaggregating or abnormally aggregating mutants, showed poor FrzCD methylation. The well-characterized asg, bsg, csg, and esg mutants were found to be of this type. The defects in FrzCD methylation of these signaling mutants could be partially rescued by extracellular complementation with wild-type cells or addition of chemicals which restore their fruiting body formation. Mutants blocked in late development, i.e., translucent mounds, showed normal FrzCD methylation. Surprisingly, some mutants blocked in early development also exhibited a normal level of FrzCD methylation. The characterized mutants in this group were found to be defective in social motility. This indicates that FrzCD methylation defines a discrete step in the development of M. xanthus and that social motility mutants are not blocked in these early developmental steps.

Bacterial Proteins↗
PubMed2004

Whole blood and leukocyte RNA isolation for gene expression analyses.

The analysis of gene expression data in clinical medicine has been plagued by the lack of a critical evaluation of accepted methodologies for the collection, processing, and labeling of RNA. In the present report, the reliability of two commonly used techniques to isolate RNA from whole blood or its leukocyte compartment was compared by examining their reproducibility, variance, and signal-to-noise ratios. Whole blood was obtained from healthy subjects and was either untreated or stimulated ex vivo with Staphylococcus enterotoxin B (SEB). Blood samples were also obtained from trauma patients but were not stimulated with SEB ex vivo. Total RNA was isolated from whole blood with the PAXgene proprietary blood collection system or from isolated leukocytes. Biotin-labeled cRNA was hybridized to Affymetrix GeneChips. The Pearson correlation coefficient for gene expression measurements in replicates from healthy subjects with both techniques was excellent, exceeding 0.985. Unsupervised analyses, including hierarchical cluster analysis, however, revealed that the RNA isolation method resulted in greater differences in gene expression than stimulation with SEB or among different trauma patients. The intraclass correlation, a measure of signal-to-noise ratio, of the difference between SEB-stimulated and unstimulated blood from healthy subjects was significantly higher in leukocyte-derived samples than in whole blood: 0.75 vs. 0.46 (P = 0.002). At the P < 0.001 level of significance, twice as many probe sets discriminated between SEB-stimulated and unstimulated blood with leukocyte isolation than with PAXgene. The findings suggest that the method of RNA isolation from whole blood is a critical variable in the design of clinical studies using microarray analyses.

Adolescent↗
PubMed1997

Percutaneous interventions to support failing hemodialysis fistulas and grafts.

Different methods of percutaneous management offer an approach to nearly every type of failing hemodialysis fistula. Technically, shunt intervention is highly successful and associated with a low complication rate. It is quick, inexpensive and can be performed on an outpatient basis with immediate dialysis via the fistula thereafter. Nearly all techniques of interventional radiology have their place in this strategy and skilled training is mandatory to achieve excellent results. Reobstruction has to be accepted as part of the process. Frequent but timely reintervention is therefore part of shunt maintenance and protection.

Angioplasty, Balloon↗
PubMed1999

Induction of interleukin-6 expression by angiotensin II in rat vascular smooth muscle cells.

Recent studies suggest that atherosclerosis is a kind of inflammatory process and that cytokine plays important roles in this process. Although it is generally accepted that angiotensin II (Ang II) plays an important role in atherogenesis, the role of Ang II in cytokine production has not been explored. In this report, we investigated the effect of Ang II on the production of interleukin-6 (IL-6), which is a multifunctional proinflammatory cytokine in rat vascular smooth muscle cells. Ang II significantly increased the expression of IL-6 mRNA and protein in a dose-dependent manner (10(-10) to 10(-6) mol/L). The expression of IL-6 mRNA induced by Ang II showed 2 peaks at 30 minutes and 12 to 24 hours after stimulation. The effect of Ang II on IL-6 release and mRNA expression was completely blocked by an Ang II type 1 receptor antagonist, CV11974; however, an Ang II type 2 receptor antagonist, PD123319, showed no effect. Chelating of intracellular Ca(2+) with BAPTA-AM, inhibition of tyrosine kinase with genistein, and inhibition of mitogen-activated protein kinase kinase with PD98059 completely abolished the effect of Ang II. However, downregulation of protein kinase C by pretreatment with a phorbol ester for 24 hours or a specific protein kinase C inhibitor, calphostin C, did not affect the Ang II-induced expression of IL-6 mRNA. Deletion and mutational analysis of IL-6 gene promoter showed that cAMP-responsive element was important for Ang II-induced IL-6 gene expression. Gel mobility shift assay showed an increase of cAMP-responsive element binding protein by Ang II. These results provide new insights into Ang II signaling and the role of Ang II in the progression of inflammatory changes of blood vessels.

Angiotensin II↗
PubMedDate not supplied

Leadership for psychiatrists.

OBJECTIVE: This article introduces the prospective leader to a set of questions and relevant leadership literature that aid in the process of deciding whether to accept a leadership position. METHOD: The author conducted a review of literature and discussion with leaders in psychiatry and other medical disciplines. RESULTS: The questions posed and leadership literature discussed provide a useful set of guidelines for potential leaders in deciding whether to accept or continue in a leadership position. CONCLUSIONS: Having access to mentoring, a clear description of "expected results," personal appreciation of leadership style, a description of available resources, a leadership vision in line with the institutional vision, and an appreciation of the necessary time commitments are fundamental in deciding whether to accept a leadership position.

Academic Medical Centers↗
PubMed1993

Preferences of agency administrators and state and local officials about mental health site evaluation visits.

OBJECTIVE: To explore changing the procedures for site reviews of mental health facilities in New Jersey, the study sought to determine the views of administrators of mental health agencies and of state and county mental health officials about evaluation methods used by site visit teams. METHODS: Response to a 35-item questionnaire by 86 provider-agency administrators were compared with responses by 34 government officials using chi square analysis and two-way analyses of variance. RESULTS: Both agency administrators and government officials believed that the primary purpose of site visits was to improve service quality and assess compliance with standards of good care. Compared with agency administrators, government officials viewed site visits as more useful and important. Agency administrators believed that identifying problems not under the agency's control was the most useful feature of a site visit. Although both groups apparently wanted consumers' input during the evaluation process, both were hesitant to accept consumers and their families as members of site visit teams. CONCLUSIONS: Both groups favored changes that would make site visits a more collaborative enterprise. Their similar views on many issues form a core of agreement about site visit procedures around which further consensus can be built.

Community Mental Health Centers↗
PubMed2006

Innovations in mental health services implementation: a report on state-level data from the U.S. Evidence-Based Practices Project.

BACKGROUND: The Evidence-Based Practice (EBP) Project has been investigating the implementation of evidence-based mental health practices (Assertive Community Treatment, Family Psychoeducation, Integrated Dual Diagnosis Treatment, Illness Management and Recovery, and Supported Employment) in state public mental health systems in the United States since 2001. To date, Project findings have yielded valuable insights into implementation strategy characteristics and effectiveness. This paper reports results of an effort to identify and classify state-level implementation activities and strategies employed across the eight states participating in the Project. METHODS: Content analysis and Greenhalgh et al's (2004) definition of innovation were used to identify and classify state-level activities employed during three phases of EBP implementation: Pre-Implementation, Initial Implementation and Sustainability Planning. Activities were coded from site visit reports created from documents and notes from key informant interviews conducted during two periods, Fall 2002-Spring 2003, and Spring 2004. Frequency counts and rank-order analyses were used to examine patterns of implementation activities and strategies employed across the three phases of implementation. RESULTS: One hundred and six discreet implementation activities and strategies were identified as innovative and were classified into five categories: 1) state infrastructure building and commitment, 2) stakeholder relationship building and communications, 3) financing, 4) continuous quality management, and 5) service delivery practices and training. Implementation activities from different categories were employed at different phases of implementation. CONCLUSION: Insights into effective strategies for implementing EBPs in mental health and other health sectors require qualitative and quantitative research that seeks to: a) empirically test the effects of tools and methods used to implement EBPs, and b) establish a stronger evidence-base from which to plan, implement and sustain such efforts. This paper offers a classification scheme and list of innovative implementation activities and strategies. The classification scheme offers potential value for future studies that seek to assess the effects of various implementation processes, and helps establish widely accepted standards and criteria that can be used to assess the value of innovative activities and strategies.

Journal Article↗
PubMed1999

Lost in the mall: misrepresentations and misunderstandings.

Readers of Ethics and Behavior have been treated to a misrepresentation of my research on planting false memories, to a misstatement of the actual empirical finidngs, and to a distortion of the history of the development of the idea for this line of research. The partisan essay by Crook and Dean which appears in this issue ("'Lost in a Shopping Mall' -- A Breach of Professional Ethics") is disturbing not only because of its errors, exaggerations, and omissions, but because, in some instances, the quality of the argument makes one wonder whether these were innocent mistakes or a deliberate attempt to distort my work. Some of these errors can be explained by simple lack of scientific competence. However, others are sufficiently bizarre that they cast doubt on the process that led to the acceptance of a manuscript written by an individual who has continually made her animosity toward me very publicly known (e.g., Boerner, 1996; Neimark, 1996).

Adult↗
PubMed2006

Resisting good news: reactions to breast cancer risk communication.

Many women overestimate their percentage risk of breast cancer, even after they have received careful estimates from health professionals. In 2 experiments with 134 young adult women, 6 variables were explored that might influence such risk perception persistence. In Study 1, each of the following explanations was unrelated to persistence: public commitment, self-consistency, and unique causal risk models. In Study 2, two individual difference measures, pessimism and differences in understanding percentages, were unrelated to risk perception persistence. However, providing a "risk anchor" based on downward social comparison processes resulted in better risk acceptance at posttest that persisted at a 2-week follow-up assessment. This article discusses why comparison anchors might be important in risk feedback situations and concludes with recommendations for professionals who wish to provide accurate risk information and have patients adopt that information.

Adult↗
PubMed2006

Activation function 1 of glucocorticoid receptor binds TATA-binding protein in vitro and in vivo.

The mechanism through which the glucocorticoid receptor (GR) stimulates transcription is still unclear, although it is clear that the GR affects assembly of the transcriptional machinery. The binding of the TATA-binding protein (TBP) to the TATA-box is accepted as essential in this process. It is known that the GR can interact in vitro with TBP, but the direct interaction of TBP with GR has not been previously characterized quantitatively and has not been appreciated as an important step in assembling the transcriptional complex. Herein, we demonstrate that the TBP-GR interaction is functionally significant by characterizing the association of TBP and GR in vitro by a combination of techniques and confirming the role of this interaction in vivo. Combined analysis, using native gel electrophoresis, sedimentation equilibrium, and isothermal microcalorimetry titrations, characterize the stoichiometry, affinity, and thermodynamics of the TBP-GR interaction. TBP binds recombinant GR activation function 1 (AF1) with a 1:2 stoichiometry and a dissociation constant in the nanomolar range. In vivo fluorescence resonance energy transfer experiments, using fluorescently labeled TBP and various GR constructs, transiently transfected into CV-1 cells, show GR-TBP interactions, dependent on AF1. AF1-deletion variants showed fluorescence resonance energy transfer efficiencies on the level of coexpressed cyan fluorescent protein and yellow fluorescent protein, indicating that the interaction is dependent on AF1 domain. To demonstrate the functional role of the in vivo GR-TBP interaction, increased amounts of TBP expressed in vivo stimulated expression of GR-driven reporters and endogenous genes, and the effect was also specifically dependent on AF1.

Animals↗
PubMed2003

The role of annexin 2 in osteoblastic mineralization.

While the basic cellular contributions to bone differentiation and mineralization are widely accepted, the regulation of these processes at the intracellular level remains inadequately understood. Our laboratory recently identified annexin 2 as a protein involved in osteoblastic mineralization. Annexin 2 was overexpressed twofold in SaOSLM2 osteoblastic cells as a fusion protein with green fluorescent protein. The overexpression of annexin 2 led to an increase in alkaline phosphatase activity as well as an increase in mineralization. Our data suggest that the increase in alkaline phosphatase activity does not result from increased alkaline phosphatase transcript or protein levels; therefore we evaluated mechanism of action. We determined that both annexin 2 and alkaline phosphatase activity were localized to membrane microdomains called lipid rafts in osteoblastic cells. Annexin 2 overexpression resulted in an increase in alkaline phosphatase activity that was associated with lipid microdomains in a cholesterol-dependent manner. Furthermore, disruption of lipid rafts with a cholesterol sequestering agent or reduction of annexin 2 expression by specific antisense oligonucleotides each resulted in diminished mineralization. Therefore, intact lipid rafts containing annexin 2 appear to be important for alkaline phosphatase activity and may facilitate the osteoblastic mineralization process.

Alkaline Phosphatase↗
PubMed2006

[Mechanism of cell proliferation--cell cycle, oncogenes, and senescence].

Cell proliferation is regulated through a transition between the G0 phase and cell cycle. We isolated a mammalian temperature-sensitive mutant cell line defective in the function from the G0 phase to cell cycle. Senescent human somatic cells fail to enter into the cell cycle from the G0 phase with stimulation by any growth factor. Telomere shortening was found to be a cause of cellular senescence, and reexpression of telomerase immortalized human somatic cells. Immortalized human somatic cells showed normal phenotypes and were useful not only for basic research but also for clinical and applied fields. The importance of p53 and p21 activation/induction i now well accepted in the signal transduction process from telomere shortening to growth arrest, but the precise mechanism is largely unknown as yet. We found that the MAP kinase cascade and histone acetylase have an important role in the signaling process to express p21. Tumor tissues and cells were found to have strong telomerase activity, while most normal somatic human tissues showed very weak or no activity. Telomerase activity was shown to be a good marker for early tumor diagnosis because significant telomerase activity was detected in very early tumors or even in some precancerous tissues compared with adjacent normal tissues. Telomere/telomerase is a candidate target for cancer chemotherapeutics, and an agent that abrogated telomere functions was found to kill tumor cells effectively by inducing apoptosis whereas it showed no effect on the viability of normal cells.

Animals↗
PubMedDate not supplied

Coronary care unit ST-trending system: interpreting complex output data.

Analysis of the ST segment is an accepted part of the assessment of coronary ischaemia. Traditionally, such analysis has been applied to 12-lead surface electrocardiograms, but it is increasingly applied to 24-hour Holter recordings and bedside monitoring systems, using complex computer algorithms. There is a potential for results to be misleading as a consequence of uncritical acceptance of complex medical data processing.

Bias↗
PubMed1999

Characteristics of peer reviewed clinical medicine journals.

Many variations exist in editorial peer review practices in clinical medicine journals. These practices will become more crucial as medical journals make more of their contents available via the World Wide Web. This paper explores five fundamental dimensions of editorial peer review variations: (1) the extent to which manuscripts are subjected to peer review; (2) the sequence of decision points in the peer review process; (3) blinding practices; (4) acceptance rates for submitted manuscripts; and (5) guidelines stating editors' expectations of reviewers. Variations in editorial peer review practices make it difficult to define a "peer reviewed journal" in clinical medicine. Research in this relatively new area of inquiry has not established the relative strengths of each variation in relation to a journal's quality.

Clinical Medicine↗
PubMed1999

[Not Available].

Psychotherapy is an interpersonal and interactive process. As this view gained acceptance, methods in psychotherapy research for analysing the intersubjective dimension of the psychotherapeutic dialogue became more important. Ethnomethodology with its research program of conversation and context analysis has a long tradition in research on social interaction and can follow this development. With a conversation analytic approach means and practices can be reconstructed that patient and therapist use to coproduce the psychotherapeutic encounter.

Conversation analysis↗
PubMed2002

Optimal method of linear regression in laser remote sensing.

Remote lidar sensing in the photon-counting mode is now the commonly accepted method for studying atmospheric processes in the lower and free atmosphere. However, when processing signals obtained from lidar measurements, investigators necessarily face the problem of achieving accuracy in reconstructing the atmospheric parameters despite the presence of inhomogeneous noise in the measured signals. We propose an optimal method of linear regression (OMLR) of signals. The accuracy of the the method for the reconstructed signal is estimated. An example of application of the OMLR to the reconstruction of the temperature profile from the data obtained with a Raman lidar at the Siberian Lidar Station of the Institute of Atmospheric Optics (Tomsk, Russia) is given. The proposed method is distinguished by simplicity of interpretation of the criteria used, based on careful adherence to statistical principles. This method is shown to be an efficient auxiliary tool for the processing of measured data.

Journal Article↗
PubMed1984

A realistic approach to locating dental practices.

A realistic approach to locating a dental practice involves the consideration of factors affecting the demand for dental services in an area. This dictates examination of the demographic and economic determinants of demand. Many retail businesses have used this approach to making locational decisions, and dentistry should benefit from this same process. If the thesis is accepted that dentistry is a business as well as a profession, it follows that the dentist-business person must be permitted, indeed expected, to make a reasonable return in revenue on the investment of dollars in education, equipment, and other related expenses. This return on investment occurs only when there is adequate patient flow. An objective procedure to assess demand for dental services at a particular location has been described. With this method, students were expected to: Visit the community and, through interviews with other professionals and knowledgeable business persons, determine the extent of the probable dental service area. The service area is circumscribed on a census map. Use the census subdivision numbers on the map to secure data from the state data center that describes the area's population, in regard to age, race, gender, income, and education. Transfer the data to a spreadsheet designed to generate total visits, according to each of the demand determinants. Calculate the number of FTE practitioners needed to meet this potential demand, and compare this with the number of FTE dentists presently practicing in the community. Fourteen senior dental students, who have since graduated, have completed this procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2006

The road map to oral bioavailability: an industrial perspective.

Optimisation of oral bioavailability is a continuing challenge for the pharmaceutical and biotechnology industries. The number of potential drug candidates requiring in vivo evaluation has significantly increased with the advent of combinatorial chemistry. In addition, drug discovery programmes are increasingly forced into more lipophilic and lower solubility chemical space. To aid in the use of in vitro and in silico tools as well as reduce the number of in vivo studies required, a team-based discussion tool is proposed that provides a 'road map' to guide the selection of profiling assays that should be considered when optimising oral bioavailability. This road map divides the factors that contribute to poor oral bioavailability into two interrelated categories: absorption and metabolism. This road map provides an interface for cross discipline discussions and a systematic approach to the experimentation that drives the drug discovery process towards a common goal - acceptable oral bioavailability using minimal resources in an acceptable time frame.

Biological Availability↗