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At least 433 records · Page 24Linked to original sources
PubMed1999

Ultrastructure and immunohistochemical identification of the extracellular matrix of the chinchilla cochlea.

The molecular composition and three-dimensional organization of the extracellular matrix (ECM) was studied by immunofluorescent microscopy, transmission and scanning electron microscopy in three connective tissue structures of the cochlea: the spiral limbus, basilar membrane and spiral ligament. Type II collagen, fibronectin, tenascin, chondroitin sulfate proteoglycans, alphav and beta1 integrins were immunolocalized in the ECM of these connective tissue structures. Electron micrographs showed a continuum of cross-striated collagen fibrils having a similar diameter and axial periodicity that spread from the spiral limbus via the basilar membrane and into the spiral ligament. Some of collagen fibrils were aggregated laterally into bundles. Bundle images, and their digital Fourier transformations, showed a major 67-nm axial D-repeat characteristic for collagen fibrils. Transmission electron microscopy showed numerous proteoglycans associated with the collagen fibrils. The spiral limbus, basilar membrane and spiral ligament demonstrated regional differences in molecular composition and structural organization of their ECM. The glycoproteins fibronectin, tenascin and alphav integrin were immunolocalized mainly in the basilar membrane. Collagen fibrils of the spiral limbus and spiral ligament did not appear to be strongly oriented. However, most of the collagen fibrils in the basilar membrane were arranged into radially directed bundles. Collagen fibrils in the basilar membrane were also surrounded by a homogeneous matrix, which was immunoreactive to fibronectin and tenascin antibodies. A more complete understanding of the composition and structural organization of the ECM in these connective tissue structures in the cochlea provides a foundation upon which micromechanical models of cochlear function can be constructed.

Animals↗
PubMed2003

A mutagenesis study of the putative luciferin binding site residues of firefly luciferase.

Firefly luciferase catalyzes the highly efficient emission of yellow-green light from substrate firefly luciferin by a sequence of reactions that require Mg-ATP and molecular oxygen. We had previously developed [Branchini, B. R., Magyar, R. A., Murtiashaw, M. H., Anderson, S. M., and Zimmer, M. (1998) Biochemistry 37, 15311-15319] a molecular graphics-based working model of the luciferase active site starting with the first X-ray structure [Conti, E., Franks, N. P., and Brick, P. (1996) Structure 4, 287-298] of the enzyme without bound substrates. In our model, the luciferin binding site contains 15 residues that are within 5 A of the substrate. Using site-directed mutagenesis, we made changes at all of these residues and report here the characterization of the corresponding expressed and purified proteins. Of the 15 residues studied, 12 had a significantly (>or=4-fold K(m) difference) altered binding affinity for luciferin and seven residues, spanning the primary sequence region Arg218-Ala348, had substantially (>or=30 nm) red-shifted bioluminescence emission maxima when mutated. We report here an interpretation of the roles of the mutated residues in substrate binding and bioluminescence color determination. The results of this study generally substantiate the accuracy of our model and provide the foundation for future experiments designed to alter the substrate specificity of firefly luciferase.

Animals↗
PubMed1996

Influenza-virus-liposome lipid mixing is leaky and largely insensitive to the material properties of the target membrane.

Monolayer intrinsic curvature, void stabilization, and membrane rupture tension have been suggested as important factors determining the rate of membrane fusion. Here, we have studied the kinetics of fusion between influenza virus and target liposomes as a function of various target membrane material properties. In order to examine the fusion process directly, a simple prebinding step is used and proven to be adequate to achieve fusion-rate-limiting kinetics. To test the hypothesis about membrane curvature and void stabilization, we studied the lipid mixing kinetics with dioleoylphosphatidylcholine (DOPC)/ganglioside GD1a (GD1a) liposomes containing lysooleoylphosphatidylcholine (LPC, positive curvature), dioleoyglycerol (DOG, negative curvature), arachidonic acid (AA, negative curvature), and hexadecane (HD, void stabilization). DOG, AA, and HD (at 4 mol%) showed no significant effect on the fusion kinetics, while LPC reversibly inhibited influenza HA mediated fusion only at very high concentrations. Using target liposomes with different membrane rupture tension values, no obvious correlation between membrane rupture tension and the rate of lipid mixing was observed. Moreover, a reported potential antiviral compound, tert-butylhydroquinone (t-b-HQ) (Bodian et al., 1993), showed no significant effect on the kinetics of influenza fusion. Finally leakage of liposome contents was detected during lipid mixing. For encapsulated molecules smaller than 450 MW, the kinetics of leakage is very similar to the kinetics of lipid mixing. In fact, leakage was also detected for encapsulated molecules up to 10 000 MW, suggesting that HA mediated lipid mixing is a very leaky process. Since "nonleaky fusion" has been the foundation of influenza fusion models, our work suggests the need for a major revision in the modeling of this process.

Influenza A virus↗
PubMed1988

An implantable pump for intrarenal infusion of immunosuppressants in a canine autotransplant model.

We developed a canine renal allograft model utilizing implantable infusion pumps and biocompatible catheters to investigate the pharmacokinetics of local immunosuppressive drug administration. Seven mongrel dogs underwent bilateral nephrectomy and autotransplantation of one kidney to the iliac vessels. The proximal end of an infusion catheter directed into the iliac artery was tunneled to a subcutaneously placed programmable pump. A second, sampling catheter was placed with its tip in the iliac vein. Simultaneous regional (iliac vein) and systemic (jugular vein) venous concentrations of 6-mercaptopurine (6-MP), the immunosuppressive metabolite of azathioprine, were determined during a continuous 24-h intraarterial infusion (10 mg/kg/24 hr). The gradient between regional and systemic 6-MP concentrations was maximal initially when the pump was turned on, continuously decreased until steady state was reached, and disappeared immediately after the pump was turned off. The mean ratio of steady-state iliac vein to systemic 6-MP concentrations was 5.0 +/- 1.4, demonstrating a pharmacokinetic advantage of continuous intraarterial 6-MP infusion to the autotransplanted kidney. The novel canine renal allograft model described herein overcomes the technical limitations of earlier models and represents a foundational step in the design of intrarenal infusion patterns of immunosuppressive agents which we expect to prolong survival of the allotransplanted kidney with minimal systemic drug exposure and side effects.

Animals↗
PubMed1998

Dose-dependence and repeated-dose studies for receptor/gene-mediated pharmacodynamics of methylprednisolone on glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver.

Dose-dependent and repeated-dose effects of methylprednisolone (MPL) on down-regulation of glucocorticoid receptor messenger RNA (GR mRNA) and GR density, as well as tyrosine aminotransferase (TAT) mRNA and TAT induction by receptor/gene-mediated mechanisms in rat liver were examined. A previously developed pharmacokinetic/pharmacodynamic (PK/PD) model was used to design these studies which sought to challenge the model. Three groups of male adrenalectomized Wistar rats received MPL by i.v. injection: low-dose (10 mg/kg at Time 0), high-dose (50 mg/kg at Time 0), and dual-dose (50 mg/kg at Time 0 and 24 hr). Plasma concentrations of MPL, and hepatic content of free GR, GR mRNA, TAT mRNA, and TAT activity were determined. The P-Pharm program was applied for population analysis of MPL PK revealing low interindividual variation in CL and Vc values (3-14%). Two indirect response models were applied to test two competing hypotheses for GR mRNA dynamics. Indirect Pharmacodynamic Response Model I (Model A) where the complex in the nucleus decreases the transcription rate of GR mRNA better described GR mRNA/GR down-regulation. Levels of TAT mRNA began to increase at 1-2 hr, reached a maximum at 5-6 hr, and declined to the baseline at 12-14 hr after MPL dosing. The induction of TAT activity followed a similar pattern with a delay of about 1-2 hr. The low-dose group had 50-60% of the TAT mRNA and TAT induction compared to the high-dose group. Since the GR density returned to about 70% of the baseline level before the second 50 mg/kg dose at 24 hr, tolerance was found for TAT mRNA/TAT induction where only 50-60% of the initial responses were produced. Our fourth-generation model describes the dose dependence and tolerance effects of TAT mRNA/TAT induction by MPL involving multiple-step signal transduction controlled by the steroid regimen, free GR density, and GR occupancy. This model may provide the foundation for studying other induced proteins or enzymes mediated by the similar receptor/nuclear events.

Animals↗
PubMed2004

Managing team interpersonal processes through technology: a task-technology fit perspective.

This article addresses the broad question, How can virtual teams that manage a majority of their interactions through information and communication technologies (ICTs) be made more effective? Focusing specifically on interpersonal interactions, the task-technology fit paradigm is used as the foundation for a theoretical model that seeks to identify how such teams can match available communication technologies to the different types of interpersonal interactions in which they engage. The authors draw on media synchronicity theory to identify the functionalities of the wide range of ICTs available today, and map these functionalities onto the salient communication needs of 3 key interpersonal processes: (a) conflict management, (b) motivation and confidence building, and (c) affect management. The model also incorporates a temporal dimension examining how the communication needs, and hence, the need for ICT functionality, varies depending on the virtual team's developmental stage. Opportunities for future research arising from the theoretical model are discussed.

Conflict, Psychological↗
PubMed1999

Guide to practice or 'load of rubbish'? The influence of care plans on nursing practice in five clinical areas in Northern Ireland.

A nursing care plan is a written, structured plan of action for patient care. There is strong evidence that care plans are viewed negatively by nurses and poorly implemented, with little evidence to suggest that they have any positive effect on quality of care or patient outcomes. The project reported in this paper aimed to investigate how nursing care plans were being used in five clinical areas, and to assess their influence on nursing practice. An exploratory, predominantly qualitative research design was selected utilizing participant observation, focus groups and diaries. In four of the five clinical areas, the 'activities of daily living' section of care plans had no apparent positive influence on nursing practice which was driven by other factors and sources of information. Care plans in the remaining ward were clinically led and locally owned, and in this setting they operated as an important guide to practice. It is concluded that a reinvention of the nursing care plan is needed without the constraint of a nursing model as its necessary foundation. New and imaginative plans of action for patient care should be encouraged, developed at ward level and tailored to the demands of the clinical area. These should contain a minimum of documentation and integrate with nursing practice.

Adult↗
PubMed2002

[Job satisfaction in rehabilitation clinics--Development of the "MiZu-Reha" questionnaire and its use in quality assurance].

In this study, we report on the development and validation of a questionnaire measuring job satisfaction in rehabilitation centres. The questionnaire "Fragebogen zur Mitarbeiterzufriedenheit in Rehabilitationskliniken" ("MiZu-Reha") consists of 75 items. Three scales measure work climate, leadership and work organisation/communication. Further items assess weak points of work organisation and job satisfaction with several predefined aspects (e. g., career opportunities and salary). The scales have good internal consistency with Cronbach's alpha between 0.86 and 0.94. The dimensionality of the scales was established by confirmatory factor analyses. Correlations between the MiZu-Reha scales and independent satisfaction measures indicate the validity of the questionnaire. Correlations between the MiZu-Reha scales and indicators of patient satisfaction, process quality and outcome are in all cases positive (the higher the job satisfaction, the better the quality of rehabilitation), though weak and statistically not significant. Rehabilitation centres differ clearly from each other regarding job satisfaction of their employees. This shows the usefulness of clinic comparisons based on the MiZu-Reha. The questionnaire can be utilized in external quality assurance programmes, in the context of internal quality assurance measures (e. g. the Business Excellence Model of the European Foundation of Quality Management, EFQM) and in the use of management instruments such as the Balanced Scorecard.

Adult↗
PubMed2005

Experiencing release: sex environments and escapism for HIV-positive men who have sex with men.

There are nonsexual reasons that may motivate people to seek out sexual activity with others. Some men who have sex with men may seek out sex environments to engage in sexual behavior. Among the nonsexual reasons that exist for men who have sex with men is a desire to escape from distressing thoughts and feelings. The amplified sexuality and other unique characteristics of sex environments allow men to have more intense emotional experiences around sex. Using the cognitive escape model as a theoretical foundation, this analysis focuses on the emotional vulnerability that some of the men who visit these venues may be avoiding and how their experiences at these venues might act as releasing mechanisms to alleviate dissonant thoughts and feelings. Implications for public health services and future research are discussed.

Adult↗
PubMed1999

Postanalytical factors and their influence on analytical quality specifications.

Quality thinking in medical laboratories is placed within the framework of the European Foundation for Quality Management Model which suggests the use of medical outcome indicators such as those developed by the Joint Commission on Accreditation of Healthcare Organizations. From here concepts were illustrated to improve the quality of the medical laboratory towards the data produced but moreover towards the information given, the knowledge acquired and the decision taken. Postanalytical factors were used to define analytical quality specifications.

Clinical Laboratory Techniques↗
PubMed2004

Alcohol and violence: connections, evidence and possibilities for prevention.

This article reviews a number of theoretical and substantive arguments and models concerning the link between alcohol and violent crime which have appeared in the research literature in the past decade. These arguments and models form a firm foundation for the expectation that alcohol plays a causal role in violent crime, and that interventions designed to reduce or eliminate this link between alcohol and violence have the potential to become effective violence prevention policies. Four studies on the relationship between alcohol and violence are summarized, including one in which a natural alcohol policy experiment is evaluated. Taken together, these studies provide substantial empirical evidence that alcohol policy can be an effective crime prevention tool.

Alcohol Drinking↗
PubMed2000

Genetic correction of inherited epidermal disorders.

Genetic correction of monogenic human skin disorders represents a potentially effective molecular therapy for severe diseases in which current therapy is only palliative. The stratified epithelium of the epidermis represents the tissue location with the largest number of genetic skin diseases yet characterized. Specific requirements of successful gene delivery in this setting include correct targeting within tissue, durability, and a lack of immunogenecity. Progress toward this goal has advanced from identification of disease genes to reintroduction of wild-type genes to patient cell lines and primary cells in vitro. This initial work has been extended to gene-based correction of diseased tissue regenerated in vivo in the form of human patient skin xenografts on immune-deficient mice. Efforts in this human tissue model have laid the foundation for future efforts to extend this progress toward ex vivo cutaneous gene therapy trials in humans.

Animals↗
PubMed2026

ChromBERT-tools: a versatile toolkit for context-specific regulatory representations of transcription regulators across different cell types.

SUMMARY: Representations that encode the genome-wide regulatory behavior of transcription regulators provide a foundation for flexible transcription modeling and in silico regulatory analysis. Existing regulator representations are commonly derived from gene co-expression, motif annotations, or static protein features, which capture useful but limited aspects of regulator identity but do not directly model how regulators participate in region-specific regulatory programs across the genome. ChromBERT addresses this gap by learning context-aware regulatory representations from large-scale ChIP-seq data. However, routine bioinformatics applications require lightweight, accessible, and modular tools for generating, adapting, and interpreting these representations in user-defined biological contexts. Here, we present ChromBERT-tools, a user-oriented toolkit built upon ChromBERT that converts its regulatory representation framework into practical workflows for customizable analysis across cellular contexts. ChromBERT-tools provides command-line interfaces and Python APIs organized into three functional layers: representation generation, predictive modeling, and regulatory interpretation. The representation generation layer produces representations of genomic regions and transcription regulators. The predictive modeling layer fine-tunes ChromBERT for genome-wide regulatory activity prediction through classification or regression tasks, with optimized implementation to reduce running time and computational resource requirements. The regulatory interpretation layer supports inference of the context-specific roles of cis-regulatory elements and transcription regulators. These modules can be used independently or integrated into end-to-end workflows, enabling flexible analyses across diverse datasets. ChromBERT-tools lowers the barrier to applying context-specific regulatory representations in routine genomic analyses. AVAILABILITY AND IMPLEMENTATION: ChromBERT-tools is freely available at https://github.com/TongjiZhanglab/ChromBERT-tools, with documentation at https://chrombert-tools.readthedocs.io/en/latest/. A frozen archival snapshot is available on Zenodo under DOI: 10.5281/zenodo.20094206.

Software↗
PubMedDate not supplied

Bacterial endotoxins and pathogenesis.

Recent advances in endotoxin biochemistry, cell biology, and immunopathology are reviewed. Discussion is focused on the endotoxin-unresponsive C3H/HeJ mouse and the contributions the studies of this mouse have made to current concepts of the mechanisms of endotoxin action. The extension of the observations documented with this experimental model provide a firm foundation for productive future research into the precise role of bacterial endotoxins in the protection against, and exacerbation of, gram-negative bacterial sepsis.

Animals↗
PubMed1992

The structure and process of AIDS case management.

This article presents observations of case management in the Robert Wood Johnson Foundation AIDS Health Services Program. Case management is discussed in terms of assessment, care plan development, client links with services, monitoring, and advocacy. Recommendations are proposed to ensure that AIDS case management is delivered in a standard and equitable manner that can be monitored by quality assurance agencies.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Organizing for communication and integration.

Using the departmental philosophy as its foundation, an integrated organizational model was designed for a nursing department. This patient-centered model was implemented to streamline operations, focus resources, and provide a professional practice environment for nursing staff. The "molecule" is used as a teaching tool and organizational framework, with applications ranging from orientation of new staff to management of daily operations.

Communication↗
PubMed1999

Localized stresses in the intervertebral disc resulting from a loose fragment. A theory for fissure and fragment.

STUDY DESIGN: A theoretical analysis of estimate the stresses generated in the anulus fibrosus by a loose fragment. OBJECTIVES: To test the hypothesis that a fragment can generate stress concentrations in an intervertebral disc that could lead to the progression of a fissure, and to provide a theoretical foundation for the laboratory model of lumbar disc protrusion, which proposes that a fragment is formed first and that prolapse is the final event of a chronic process. SUMMARY OF BACKGROUND DATA: A laboratory model was developed by Brinckmann and Porter in 1994, which indicated that introducing a fragment into an otherwise intact disc resulted in rapid failure of the disc under physiologic loads and flexion. Identical in vitro surgery with no reintroduction of fragments did not result in failure. METHODS: A theoretical model was developed in which a spherical fragment was impressed against a plane surface, representing the inner surface of the anulus. The stiffness of the sphere and that of the surface were varied, and the stresses generated in the anulus were calculated as a function of applied load. RESULTS: The contact stress and the shear stress increased as the stiffness of the fragment approached and exceeded that of the matrix. Increases in stiffness to more than four times that of the matrix resulted in little further increase in stress. Peak shear stresses are developed in the bulk matrix beyond the point of contact between the fragment and the anulus. For relatively small forces on the fragment, these stresses were comparable with those found in diarthrodial joints. CONCLUSIONS: It is shown that a fragment in an intervertebral disc produces localized areas of increased stress. Fatigue over long periods at these stresses could result in fissuring and premature failure of the tissue.

Humans↗
PubMed1995

"I will manage": promoting continence through community education.

Urinary incontinence affects approximately 10 million Americans, mostly elderly persons in community and institutional settings. Despite the prevalence of UI and an estimated annual total cost of $ 10 billion in the United States alone, most affected persons do not seek help for incontinence. This is chiefly because of embarrassment or because they are not aware that help is available. In this article, we describe a community education and support program for persons with fecal and urinary incontinence. The program is based on the "I Will Manage" model from the Simon Foundation for Continence, founded to "increase public awareness of incontinence, remove social stigma attached to this disability, and provide education to those suffering from incontinence, their families, and the professionals responsible for their care." The program provides a comprehensive and practical framework to promote continence through community education. In this article, we outline the program and provide information we gathered from hosting it.

Adaptation, Psychological↗