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In vitro studies of epidermal antigen-presenting cells. The mixed skin lymphocyte reaction: an in vitro model for the generation of alloreactive cytotoxic T cells by human epidermal cells.

Langerhans cells and indeterminate cells are the unique antigen-presenting epidermal cells participating in human lympho-epidermal interactions. They bear class II HLA-DR molecules, can substitute for macrophages in antigen presentation, induce a T-cell proliferative response to antigens and haptens in sensitized donors, and are necessary for alloantigen T-cell activation and generation of alloreactive cytotoxic T cells in vitro. Indirect immunofluorescence and immunogold electron microscopy on class II positive epidermal cell enriched suspensions (panning, FACS) indicated two populations of DR-positive epidermal cells: strongly DR-positive cells (25-30, 8% of positive epidermal cells) and faintly DR-positive cells, with a density of surface DR sites of respectively 5 X 10(5) and 1 X 10(5). Most Langerhans cells are among this second group while indeterminate cells are usually strongly DR-positive. OKT6-labelled cells were only typical Langerhans cells.

Animals↗

Influence of implant length and bicortical anchorage on implant stress distribution.

BACKGROUND: Short implants present superior failure rates for everybody. PURPOSE: The aim of this theoretic study was to assess to what extent implant length and bicortical anchorage affect the way stress is transferred to implant components, the implant proper, and the surrounding bone. MATERIALS AND METHODS: Stress analysis was performed using finite element analysis. A three-dimensional linear elastic model was generated. All implants modeled were of the same diameter (3.75 mm) but varied in length, at 6, 7, 8, 9, 10, 11, and 12 mm (Brånemark System, Nobel Biocare AB, Gothenburg, Sweden). Each implant was modeled with a titanium abutment screw and abutment, a gold cylinder and prosthetic screw, and a ceramic crown. The implants were seated in a supporting bone structure consisting of cortical and cancellous bone. An occlusal load of 100 N was applied at a 30 degrees angle to the buccolingual plane. RESULTS: With the selected model and bone properties, the coronal cortical anchorage was dominating, and the bone stress concentrated to that area. CONCLUSIONS: The maximum bone stress was virtually constant, independent of implant length and bicortical anchorage. The maximum implant stress, however, increased somewhat with implant length and bicortical anchorage.

Bone and Bones↗

Targeted drug aerosol deposition analysis for a four-generation lung airway model with hemispherical tumors.

One important research area of broad interest is the development of highly efficient drug delivery systems for desired site deposition and uptake. For example, controlled drug aerosol release and targeting to specific regions of the lung is a novel way to combat lung diseases, diabetes, virus infections, cancers, etc. Determination of feasible air-particle streams is a prerequisite for the development of such delivery devices, say, smart inhalers. The concept of "controlled particle release and targeting" is introduced and results are discussed for a representative model of bronchial lung airways afflicted with hemispherical tumors of different sizes and locations. It is shown that under normal particle inlet conditions a particle mass fraction of only up to 11% may deposit on the surface of a specific tumor with critical radius r/R approximately 1.25, while a controlled particle release achieves deposition fractions of 35 to 92% for a realistic combination of inlet Stokes and Reynolds numbers, depending mainly on tumor size. Furthermore, with the controlled release and targeting approach nearby healthy tissue is hardly impacted by the typically aggressive drug aerosols. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting micron-particles in sequentially bifurcating rigid airways, the results were obtained using a validated commercial finite-volume code with user-enhanced programs on a high-end engineering workstation. The new concept is generic and hence should be applicable to other regions of the respiratory system as well.

Administration, Inhalation↗

Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies.

Mouse models mimicking human diseases are important tools in trying to understand the underlying mechanisms of many disease states. Several surgical models have been described that mimic human myocardial infarction (MI) and pressure-overload-induced cardiac hypertrophy. However, there are very few detailed descriptions for performing these surgical techniques in mice. Consequently, the number of laboratories that are proficient in performing cardiac surgical procedures in mice has been limited. Microarray technologies measure the expression of thousands of genes simultaneously, allowing for the identification of genes and pathways that may potentially be involved in the disease process. The statistical analysis of microarray experiments is highly influenced by the amount of variability in the experiment. To keep the number of required independent biological replicates and the associated costs of the study to a minimum, it is critical to minimize experimental variability by optimizing the surgical procedures. The aim of this publication was to provide a detailed description of techniques required to perform mouse cardiac surgery, such that these models can be utilized for genomic studies. A description of three major surgical procedures has been provided: 1) aortic constriction, 2) pulmonary artery banding, 3) MI (including ischemia-reperfusion). Emphasis has been placed on technical procedures with the inclusion of thorough descriptions of all equipment and devices employed in surgery, as well as the application of such techniques for expression profiling studies. The cardiac surgical techniques described have been, and will continue to be, important for elucidating the molecular mechanisms of cardiac hypertrophy and failure with high-throughput technology.

Anesthesia↗

Toward a comprehensive developmental model for major depression in women.

OBJECTIVE: Major depression is a multifactorial disorder with many etiologic variables that are interrelated through developmental pathways. The authors used structural equation modeling to generate a developmental model for the etiology of major depression in women. METHOD: Data from 1,942 adult female twins, interviewed up to four times over a 9-year period, were used to construct a developmental model to predict depressive episodes in the year before the most recent interview. Eighteen risk factors in five developmental tiers were considered: 1) childhood (genetic risk, disturbed family environment, childhood sexual abuse, and childhood parental loss), 2) early adolescence (neuroticism, self-esteem, and early-onset anxiety and conduct disorder), 3) late adolescence (educational attainment, lifetime traumas, social support, and substance misuse), 4) adulthood (history of divorce and past history of major depression), and 5) the last year (marital problems, difficulties, and stressful life events). RESULTS: The best fitting model included six correlations and 64 paths, provided an excellent fit to the data, and explained 52% of the variance in liability to episodes of major depression. The findings suggest that the development of risk for major depression in women results from three broad pathways reflecting internalizing symptoms, externalizing symptoms, and psychosocial adversity. CONCLUSIONS: Major depression is an etiologically complex disorder, the full understanding of which will require consideration of a broad array of risk factors from multiple domains. These results, while plausible, should be treated with caution because of problems with causal inference, retrospective recall bias, and the limitations of a purely additive statistical model.

Adult↗

[Quality of nursing care seen from the Scandinavian nurse's viewpoint].

The aim of this study was to do the nurses' perception of quality of care explicit and to describe the quality of nursing from the nurses' perspective using a grounded theory approach. Sixteen nurses in four Nordic countries were interviewed. On the basis of the analysis a system theoretical model was generated. In the model there is a core category: patient focused outcome, and three mutual dependent categories; nursing capacity, organisation and physical environment. These categories are dynamically interrelated with the categories, relation and knowing the patient. The model is discussed in relation to relevant theories.

Attitude of Health Personnel↗

Computerized generation of lesion models for evaluating subtraction radiography.

Digital subtraction radiography is a technique that has been shown to provide greater sensitivity and specificity in detecting bur-induced crestal bone change than the traditional comparison of two radiographs. It is questionable, however, to what extent these reports relate to clinical situations. A computerized method of extracting lesion areas from clinical subtraction images and imposing them on radiographs of experimental sites has been developed with the goal of producing a more relevant model for evaluating subtraction radiography. Observers were unable to distinguish between natural lesions and those produced by this method.

Alveolar Bone Loss↗

Experimental generation and computational modeling of intracellular pH gradients in cardiac myocytes.

It is often assumed that pH(i) is spatially uniform within cells. A double-barreled microperfusion system was used to apply solutions of weak acid (acetic acid, CO(2)) or base (ammonia) to localized regions of an isolated ventricular myocyte (guinea pig). A stable, longitudinal pH(i) gradient (up to 1 pH(i) unit) was observed (using confocal imaging of SNARF-1 fluorescence). Changing the fractional exposure of the cell to weak acid/base altered the gradient, as did changing the concentration and type of weak acid/base applied. A diffusion-reaction computational model accurately simulated this behavior of pH(i). The model assumes that H(i)(+) movement occurs via diffusive shuttling on mobile buffers, with little free H(+) diffusion. The average diffusion constant for mobile buffer was estimated as 33 x 10(-7) cm(2)/s, consistent with an apparent H(i)(+) diffusion coefficient, D(H)(app), of 14.4 x 10(-7) cm(2)/s (at pH(i) 7.07), a value two orders of magnitude lower than for H(+) ions in water but similar to that estimated recently from local acid injection via a cell-attached glass micropipette. We conclude that, because H(i)(+) mobility is so low, an extracellular concentration gradient of permeant weak acid readily induces pH(i) nonuniformity. Similar concentration gradients for weak acid (e.g., CO(2)) occur across border zones during regional myocardial ischemia, raising the possibility of steep pH(i) gradients within the heart under some pathophysiological conditions.

Acetates↗

Electroconvulsive therapy for seizure control: preliminary data in a new seizure generation and control model.

Electroconvulsive therapy (ECT) effect upon seizure cessation was studied in five male Wistar rats using a penicillin intracisternal injection model (which did not damage the cranial vault). Animals were observed both clinically and electrographically for seizure development. ECT was applied at varying times following onset of seizure, at varying parameters (frequency, pulsewidth, and duration). ECT affected EEG seizure pattern in several different stimulation parameter-dependent ways: (1) modulation to different pattern; (2) increased interictal time; and (3) seizure cessation. Stimulation with higher, sustained current (50 mA) led to changes in seizure amplitude; stimulation at pulses of current led to seizure frequency dimunition, and at certain characteristic pulses "capture" was seen as the EEG activity mimicked the ECT-inducing stimulation pattern. Interictal time was usually increased by sustained, continuous (rather than pulsatile) stimulation. Seizure activity was completely stopped in several instances using parameters of 800 pulses at a frequency of 200 Hz, with 2.56 ms pulsewidth and 50 mA of current (in consecutive iterations for one specimen). No ECT-related adverse effects were noted. Analogous to the heart, pacing or defibrillating the brain using external scalp electrodes may have a role in the control of otherwise intractable seizures.

Age of Onset↗