Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “model system”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources

Behavioural neuroscience and child psychopathology: insights from model systems.

We have just emerged from "the Decade of the Brain", yet in so many ways it was the "Decade of the Genome". What relevance does the remarkable advance in knowledge in genetics and neuroscience over that period have to our understanding of child psychopathology? When the complexity of the genetic systems involved in behavioural regulation of relatively simple organisms such as the nematode worm Caenorhabditis elegans or the fruitfly Drosophila melanogaster is considered, the possibility of comprehending the links from genes to behaviour in the developing child seems remote. Yet, the principles of investigation in model systems are not so different to those that should apply in humans. This review draws out the parallels, and introduces recent findings from behavioural studies of C. elegans, D. melanogaster, and the laboratory mouse, as well as humans, to illustrate the point.

Animals↗

A nonlinear spatially variant object-dependent system model for prediction of partial volume effects and scatter in PET.

Accurate quantitation of small lesions with positron emission tomography (PET) requires correction for the partial volume effect. Traditional methods that use Gaussian models of the PET system were found to be insufficient. A new approach that models the non-Gaussian object-dependent scatter was developed. The model consists of eight simple functions with a total of 24 parameters. Images of line and disk sources in circular and elliptical cylinders, and an anthropomorphic chest phantom were used to determine the parameter values. Empirical rules to determine these parameter values for various objects based on those for a reference object, a 21.5-cm circular cylinder, were also proposed. For seven spheroids and a 3.4-cm cylinder, pixel values predicted by the model were compared with the measured values. The model-to-measurement-ratio was 1.03+/-0.07 near the center of the spheroids and 0.99+/-0.03 near the center of the 3.4-cm cylinder. In comparison, the standard single Gaussian model had corresponding ratios of 1.27+/-0.09 and 1.24+/-0.03, respectively, and the corresponding ratios for a double Gaussian model were 1.13+/-0.09 and 1.05+/-0.01. Scatter fraction (28.5%) for a line source in the 21.5-cm cylinder was correctly estimated by our model. Because of scatter, we found that errors in the measurement of activity in spheroids with diameters from 0.6 to 3.4 cm were more significant than previously appreciated.

Algorithms↗

A systems model of clinical preventive care: the case of breast cancer screening among older women. For the NCI Breast Cancer Screening Consortium.

BACKGROUND: In older women covered by Medicare, relationships among physician recommendation, mammography in the past 2 years, and clinical breast examination (CBE) in the past year were systematically explored with a variety of predisposing, enabling, and situational factors identified in the Systems Model of Clinical Preventive Care. METHODS: A population-based survey of women age 65 years and older was conducted in five National Cancer Institute's Breast Cancer Screening Consortium geographic areas. Analyses focused on women with a regular physician and site of care (n = 5318). RESULTS: Physician recommendation and mammography use declined with women's increasing age and increased with income, education, and insurance. CBE and mammography increased with number of physicians and breast cancer family history; mammography use decreased with worsening health status. Recommendations were higher among physicians who were younger, female, and internists. Family practitioners were older and male; women who saw family practitioners reported characteristics associated with decreased screening-lower income, education, and insurance-and seeing only one physician. CONCLUSIONS: Public policy and health system changes that create a uniform system of finance and service performance expectations may reduce the persistent discrepancy in physician recommendation and mammography use due to sociodemographics and physician specialty.

Adult↗

Phagocytosis, an alternative model system for the study of cell adhesion.

Cell adhesion encompasses a variety of cell-cell and cell-matrix adhesive interactions. Whereas ligation of most adhesion receptors activate Rho-family GTP-binding proteins and the subsequent reorganization of the actin cytoskeleton, the molecular mechanisms involved remain poorly understood. Because phagocytosis is a spatially restricted adhesion process, it represents a simplified model system to investigate the spatio-temporal regulation of the signalling pathways that link surface adhesion receptors, small GTPases and the actin cytoskeleton. This review highlights some of the similarities between the formation and maintenance of adhesive contacts and phagocytic uptake and discusses why the study of phagocytosis can help understand more complex adhesion processes.

Actins↗

Mortality following rehabilitation in the Traumatic Brain Injury Model Systems of Care.

While many outcomes after traumatic brain injury (TBI) have been systematically investigated, the most basic of all outcomes--survival--has been neglected. The purpose of this study was to investigate mortality in a cohort of 2,178 individuals with TBI completing inpatient rehabilitation in one of 15 National Institute on Disability and Rehabilitation Research-funded TBI Model Systems of care. The study hypotheses were: (1) relative to the general population, TBI increases mortality and decreases life expectancy in individuals with TBI completing inpatient rehabilitation and surviving to one-year post-injury; and (2) within the TBI population, the risk of death is greater in certain TBI subgroups. Results indicate that individuals with TBI were twice as likely to die compared to individuals in the general population of similar age, gender and race, resulting in an estimated average life expectancy reduction of seven years for individuals with TBI. Within the TBI population, the strongest independent risk factors for death after one-year post-injury were older age and not being employed at injury, and greater disability at rehabilitation discharge. This information is important to guide decision-making for treatment, utilization of limited medical resources, and planning for ongoing health care needs and lifetime planning.

Aging↗

Evaluation of a time-resolved fluorescence microscope using a phosphorescent Pt-porphine model system.

A time-resolved fluorescence microscope is presented that allows the sensitive detection of delayed luminescent labels with decay times from one microsecond to several milliseconds. The microscope utilizes an argon ion laser chopped with an acoustooptical modulator as excitation light source in combination with a gated multichannel plate image intensifier in the image plane. A theoretical model for the detection efficiency of practically any time-resolved fluorescence microscope is verified using phosphorescent Pt-porphine-stained Sephadex beads. The detection efficiency of the presented setup was shown to be 42%, which is near the theoretical limit of 50% for non-saturated luminescent dyes. The suppression of prompt fluorescence signals was found to be 1:5,500. The Pt-porphine beads proved to be an excellent model system for time-resolved fluorescence microscopy, showing a high extinction coefficient and high phosphorescence quantum yield in aqueous environment under room temperature conditions. Furthermore, for the microscope described the decay time of the Pt-porphine beads of 47 microseconds is long enough to enable efficient suppression of the prompt fluorescence while maintaining a high excitation and emission duty cycle. This is considered to be of vital importance in order not to saturate the luminescence with the excitation intensities commonly used in fluorescence microscopy.

Efficiency↗

Ethnographic analysis of traumatic brain injury patients in the national Model Systems database.

OBJECTIVE: To compare demographics, injury characteristics, therapy service and intensity, and outcome in minority versus nonminority patients with traumatic brain injury (TBI). DESIGN: Retrospective analysis. SETTING: Twenty medical centers. PARTICIPANTS: Two thousand twenty patients (men, n=1,518; women, n=502; nonminority, n=1,168; minority, n=852) with TBI enrolled in the Traumatic Brain Injury Model Systems database. INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Age, gender, marital status, education, employment status, injury severity (based on Glasgow Coma Scale [GCS] admission score, length of posttraumatic amnesia, duration of unconsciousness), intensity (hours) of therapy rendered, rehabilitation length of stay (LOS), rehabilitation charges, discharge disposition, postinjury employment status, FIM instrument change scores, and FIM efficiency scores. Independent sample t tests were used to analyze continuous variables; chi-square analyses were used to evaluate categorical data. RESULTS DEMOGRAPHICS: overall, minorities were found to be mostly young men who were single, unemployed, and less well educated, with a longer work week if employed when injured. ETIOLOGY: motor vehicle crashes (MVCs) predominated as the cause of injury for both groups; however, minorities were more likely to sustain injury from acts of violence and auto-versus-pedestrian crashes. Minorities also had higher GCS scores on admission and shorter LOS. Rehabilitation services: significant differences were found in the types and intensity of rehabilitation services provided; these included physical therapy, occupational therapy, and speech-language pathology, but not psychology. CONCLUSION: Minority patients who sustain TBI generally tend to be young men with less social responsibility. Although MVCs predominate as the primary etiology, acts of violence and auto-versus-pedestrian incidents are more common in the minority population. Minorities tend to have higher GCS scores at admission. Also, the type and intensity of rehabilitation services provided differed significantly for the various interdisciplinary subspecialties. Rehabilitation charges, discharge disposition, and postinjury employment status were similar for the 2 groups, even though LOS is typically 3 to 4 days shorter for the minority group. A more detailed investigation is warranted to explain these findings.

Accidents, Traffic↗

Quiescent fibroblasts in a cellular model system.

Quiescent fibroblasts are non-dividing cells in a reversible postmitotic state induced by lowering the serum concentration of the medium (e.g. from 10% to 0.3%). Three to seven days after lowering the serum concentration only minor metabolic changes will take place in the cells. During this period the quiescent fibroblasts can be used experimentally in a model system for various periods of time.

Adenosine Triphosphate↗

Proline interaction with trichloromethyl and trichloromethyl peroxyl free radicals in a model system: studies about the nature of the reaction products formed.

Trichloromethyl and trichloromethyl peroxyl radicals are known to be produced during CCl4 biotransformation and are considered to be critical for deleterious effects of this haloalkane. In this work we describe our studies on the interaction of both free radicals with a lipid-soluble derivative of the amino acid proline in a model system. The analysis of the reaction products formed by gas chromatography-mass spectrometry of the sylilated derivatives revealed the formation of at least 11 reaction products under anaerobic conditions and 13 under aerobic atmosphere. All of them were tentatively identified and all but 2 were proline analogs. Only 3 incorporated in their structure CCl3 or CCl2 portions of the CCl4 molecule and, consequently, most of the adducts formed would be missed during regular procedures most toxicologists use to determine CCl4. Results were analyzed in relation to the known role of proline in collagen metabolism and of this protein in liver cirrhosis.

Benzoyl Peroxide↗

Isolated cortical granules: a model system for studying membrane fusion and calcium-mediated exocytosis.

Cortical granules are secretory vesicles bound to the inner surface of the plasma membrane of sea urchin eggs. Intact granules can be isolated by shearing away the cytoplasm of eggs which have been bonded to a protamine-coated surface. When Ca2+ is added to preparations of isolated granules the granules fuse with each other and release their contents. It is believed that isolated cortical granules may be an excellent model system for the biochemical study of exocytosis.

Animals↗

Studies of the interaction of gravity with biological membranes using alamethicin doped planar lipid bilayers as a model system.

Gravity interacts with biological systems on different levels of complexity. For the understanding of the action of gravity on such systems at higher degrees of organisation, the investigation of interactions on the membrane and even on the molecular level is crucial. To do such studies, planar lipid bilayers with incorporated transport mediating molecules, i.e. membranes of defined biochemical composition, are close to perfect model systems. In our experiments we have used painted planar lipid bilayers doped with alamethicin. Alamethicin is especially suitable for such studies because of its high sensitivity to applied external forces, which is a result of its special pore forming mechanism. Additional, different to most other transport mediating molecules, a big amount of data from the literature is available about the dependency of alamethicin pores on physical and chemical membrane parameters. We found that the conductance of alamethicin doped bilayers is dependent on the angle of the bilayer with the gravitational vector and that it furthermore can be reduced significantly under hyper gravity conditions in a centrifuge. The effect of gravity here is not an effect on the pore conductance or the membrane-aqueous solution interface, but it is due to an interaction of gravity with the pore forming mechanism, as can be shown by investigating the dependency of the alamethicin pore kinetics on the applied forces.

Alamethicin↗

Primary skin fibroblasts as human model system for proteome analysis.

Elucidation of cellular processes and their changes at the level of protein expression and post-translational modification patterns may allow identification of novel proteins and thereby mechanisms involved in the pathogenesis of multigenic diseases. The aim of this study was to test cultured, nontransformed primary fibroblasts derived from human skin biopsies as a suitable model system for proteome analysis. Therefore soluble protein fractions were separated on several overlapping ultrazoom gels covering the pH range from 3.5-9. Correlation analysis of gel-pairs revealed a highly reproducible protein expression pattern within (intra-assay) and between (inter-assay) independent experiments of a single fibroblast cell line (intra-cell line comparison). Spot intensity variations were less than a factor of two for more than 80% of identical spots. In addition, inter-cell line comparison exhibits no significant variations in spot intensities. To achieve further improvements in reproducibility we generated master gels for each pH range by combining averaged spot information derived from two different cell lines each analysed by two independent experiments using the raw master gel algorithm of the Z3 image analysis software. The resulting reference images of primary human fibroblasts provided a basis for investigating regulation by extracellular stimuli and drugs as well as their alterations in patients with different diseases.

Cells, Cultured↗

The murine myeloid cell line 32Dcl3 as a model system for studying neutrophil functions.

The murine myeloid cell line 32Dcl3 is one of the few cell lines that can terminally differentiate into neutrophils. Granulocyte colony-stimulating factor (G-CSF) drives the differentiation of these cells; therefore, G-CSF receptor signaling for neutrophil proliferation and differentiation has been studied extensively using this cell line as a model. Differentiated 32Dcl3 cells exhibit a striking morphologic similarity to normal neutrophils; however, the degree to which differentiated 32Dcl3 cells are functionally similar to normal neutrophils remains unknown. In this study, we compared the function of differentiated 32Dcl3 cells with mouse neutrophils. Our results demonstrate that a subclone of differentiated 32Dcl3 cells (32Dcl3C) exhibits normal neutrophil functions of phagocytosis, degranulation, adhesion and shape change in response to appropriate stimuli. These observations suggest that this cell line can serve as an effective model system to study similar mature neutrophil functions. However, 32Dcl3C cells fail to produce superoxide in response proper stimuli.

Animals↗

Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system.

BACKGROUND: The Cdx genes are expressed in the colorectal epithelium and are frequently downregulated during tumorigenesis. Overexpression of Cdx genes has been shown previously to result in cellular differentiation. AIM: To study expression of CDX2 in normal and neoplastic human colon using a newly isolated monoclonal antibody. To define expression of CDX1 and CDX2 in an in vitro model system of colorectal tumour progression and to ascertain whether these are subject to regulation during differentiation. METHODS: Normal and neoplastic human colon was immunostained for CDX2. CDX1 and CDX2 expression was assayed in cell lines derived from premalignant colonic adenomas by western blotting. Differentiation was induced by sodium butyrate treatment or post confluent growth, and changes in CDX expression compared with carcinoma cell lines with low levels of CDX expression. RESULTS: CDX2 protein displayed no gradient of expression within the colonic crypt. Cell lines derived from adenomas, with high levels of CDX1 and CDX2, showed no regulation of these proteins when induced to differentiate by butyrate or confluency. CDX expression in these cell lines was independent of their APC or Ras status. CDX1 and CDX2 were expressed at very low levels in some carcinoma cell lines and were modestly upregulated on differentiation but were not restored to levels seen in adenoma cells. CONCLUSION: The lack of significant regulation on cellular differentiation and the absence of a detectable gradient in the crypt implies that CDX2 may confer tissue specificity but may not play the previously suggested role in crypt patterning.

Adenoma↗

Absorption and metabolism of vitamin K in Swiss 3T3 mouse fibroblasts--a model system for study of vitamin K absorption and metabolism.

The vitamin K cycle previously described in liver has been demonstrated in Swiss 3T3 mouse fibroblasts. Vitamin K epoxide and gamma-carboxyglutamic acid were isolated from the cells and chemically characterized. Menaquinone (MK4) is also metabolized to its epoxide and vitamin K epoxide is reduced to vitamin K in these cells. Thus Swiss 3T3 mouse fibroblasts provide a useful model system for the study of vitamin K metabolism. Possible functions of the vitamin K-dependent protein(s) in fibroblasts are discussed.

1-Carboxyglutamic Acid↗

An information system model for negotiating capitation contracts.

Capitation contracts require health care organizations to negotiate on a much more sophisticated and risky level. Understanding whether a capitation contract will allow a hospital to remain financially viable while providing quality care requires estimating the number of patients to be served, the amount and types of services to be offered, and the cost to provide them. This article presents an information system model designed to assist a large hospital, not only in determining true patient cost, but also in aggregating the cost information in different ways, such as conducting a case-mix analysis, to perform a more informed quote analysis for capitated contracts.

Academic Medical Centers↗

The molecular control of normal and leukemic hematopoiesis: myeloid cells as a model system.

The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to identify the proteins that control growth and differentiation of different hematopoietic cell lineages and to discover the molecular basis of normal and abnormal cell development in blood-forming tissues. A model system with myeloid cells has shown that normal hematopoietic cells require different proteins to induce cell multiplication and cell differentiation and that a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of hematopoiesis can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature non-dividing cells, and there are different pathways of inducing differentiation. Results from studies on the molecular control of growth and differentiation in normal myeloid hematopoietic cells, on changes in the normal developmental program, and on the suppression of malignancy in myeloid leukemia have shown that (a) malignancy can be suppressed by inducing differentiation either with or without genetic changes in the malignant cells, (b) this suppression of malignancy does not have to restore all the normal controls, and (c) genetic abnormalities that give rise to malignancy, which include changes in homeobox genes, can be bypassed and their effects nullified by inducing differentiation that stops cells from multiplying.

Bone Marrow↗

Long-term medical complications after traumatic spinal cord injury: a regional model systems analysis.

OBJECTIVE: To analyze the incidence, risk factors, and trends of long-term secondary medical complications in individuals with traumatic spinal cord injury. DESIGN: Data were reviewed from the National SCI Statistical Center on annual evaluations performed at 1, 2, 5, 10, 15, and 20 years after injury on patients injured between 1973 and 1998. SETTING: Multicenter Regional SCI Model Systems. MAIN OUTCOME MEASURES: Secondary medical complications at annual follow-up years, including pneumonia/atelectasis, autonomic dysreflexia, deep venous thrombosis, pulmonary embolism, pressure ulcers, fractures, and renal calculi. RESULTS: Pressure ulcers were the most frequent secondary medical complications in all years, and individuals at significant (p < .05) risk included those with complete injuries (years 1, 2, 5, 10), younger age (year 2), concomitant pneumonia/atelectasis (year 1, 2, 5), and violent injury (years 1, 2, 5, 10). The incidence of pneumonia/atelectasis was 3.4% between rehabilitation discharge and year-1 follow-up with those most significantly at risk being older than 60 years (years 1, 2, 5, 10) and tetraplegia-complete (years 1, 2). One-year incidence of deep venous thrombosis was 2.1% with a significant decline seen at year 2 (1.2%), and individuals most significantly (p < .001) at risk were those with complete injuries (year 1). The incidence of calculi (kidney and/or ureter) was 1.5% at 1-year follow-up and 1.9% at 5 years and was more frequent in patients with complete tetraplegia. Intermittent catheterization was the most common method of bladder management among patients with paraplegia but became less common at later postinjury visits. CONCLUSIONS: Pressure ulcers, autonomic dysreflexia, and pneumonia/atelectasis were the most common long-term secondary medical complications found at annual follow-ups. Risk factors included complete injury, tetraplegia, older age, concomitant illness, and violent injury.

Adolescent↗